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DE4337271A1 - ubstd. heterocyclic carboxylic acid amides and their prepn. - Google Patents

ubstd. heterocyclic carboxylic acid amides and their prepn.

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Publication number
DE4337271A1
DE4337271A1 DE4337271A DE4337271A DE4337271A1 DE 4337271 A1 DE4337271 A1 DE 4337271A1 DE 4337271 A DE4337271 A DE 4337271A DE 4337271 A DE4337271 A DE 4337271A DE 4337271 A1 DE4337271 A1 DE 4337271A1
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DE
Germany
Prior art keywords
alkyl
alkoxy
cycloalkyl
carbamoyl
aryloxy
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
DE4337271A
Other languages
German (de)
Inventor
Klaus Dr Weidmann
Karl-Heinz Dr Baringhaus
Georg Dr Tschank
Martin Dr Bickel
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hoechst AG
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Hoechst AG
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Publication date
Application filed by Hoechst AG filed Critical Hoechst AG
Priority to DE4337271A priority Critical patent/DE4337271A1/en
Priority to ES94117018T priority patent/ES2101421T3/en
Priority to AT94117018T priority patent/ATE149486T1/en
Priority to DK94117018.5T priority patent/DK0650961T3/en
Priority to DE59401924T priority patent/DE59401924D1/en
Priority to EP94117018A priority patent/EP0650961B1/en
Priority to SG1996007114A priority patent/SG48114A1/en
Priority to PL94305646A priority patent/PL179794B1/en
Priority to IL11145494A priority patent/IL111454A/en
Priority to UA94105979A priority patent/UA41318C2/en
Priority to NZ264821A priority patent/NZ264821A/en
Priority to MYPI94002894A priority patent/MY112413A/en
Priority to AU77564/94A priority patent/AU676775B2/en
Priority to CA002134866A priority patent/CA2134866A1/en
Priority to CZ19942683A priority patent/CZ289356B6/en
Priority to ZA948580A priority patent/ZA948580B/en
Priority to NO944162A priority patent/NO301880B1/en
Priority to KR1019940028871A priority patent/KR950014072A/en
Priority to CN94117623A priority patent/CN1107145A/en
Priority to JP6292032A priority patent/JPH07228571A/en
Priority to TW083111257A priority patent/TW399046B/en
Publication of DE4337271A1 publication Critical patent/DE4337271A1/en
Priority to GR970400831T priority patent/GR3023174T3/en
Priority to HK98105872A priority patent/HK1006711A1/en
Priority to CY9800039A priority patent/CY2120B1/en
Withdrawn legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C07D213/82—Amides; Imides in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/89—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
    • C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06139—Dipeptides with the first amino acid being heterocyclic

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Novel Substd. heterocyclic carboxylic acid amides are useful as medicaments

Description

Die Erfindung betrifft substituierte heterocyclische Carbonsäureamide, ihre Herstellung und ihre Verwendung als Inhibitoren der Prolyl-4-hydroxylase und ihre Verwendung als Arzneimittel zur Behandlung von fibrotischen Erkrankungen.The invention relates to substituted heterocyclic carboxamides, their Production and their use as inhibitors of prolyl-4-hydroxylase and their use as medicines for the treatment of fibrotic Diseases.

Verbindungen, die die Enzyme Prolin- und Lysinhydroxylase inhibieren, bewirken eine sehr selektive Hemmung der Kollagenbiosynthese durch Beeinflussung der kollagenspezifischen Hydroxylierungsreaktionen. In deren Verlauf wird proteingebundenes Prolin oder Lysin durch die Enzyme Prolin- bzw. Lysinhydroxylase hydroxyliert. Wird diese Reaktion durch Inhibitoren unterbunden, so entsteht ein nicht funktionsfähiges, unterhydroxyliertes Kollagenmolekül, das von den Zellen nur in geringer Menge in den extrazellulären Raum abgegeben werden kann. Das unterhydroxylierte Kollagen kann außerdem nicht in die Kollagenmatrix eingebaut werden und wird sehr leicht proteolytisch abgebaut. Als Folge dieser Effekte verringert sich insgesamt die Menge des extrazellulär abgelagerten Kollagens.Compounds that inhibit the enzymes proline and lysine hydroxylase a very selective inhibition of collagen biosynthesis by influencing the collagen-specific hydroxylation reactions. In the course of which protein-bound proline or lysine through the enzymes proline or Lysine hydroxylase hydroxylated. This reaction is caused by inhibitors prevented, so a non-functional, under hydroxylated Collagen molecule that is only present in small amounts in the extracellular cells Space can be given. The under-hydroxylated collagen can also cannot be built into the collagen matrix and becomes proteolytic very easily reduced. As a result of these effects, the amount of extracellularly deposited collagen.

Inhibitoren der Prolylhydroxylase sind deshalb geeignete Substanzen in der Therapie von Erkrankungen, in denen die Ablagerung von Kollagenen maßgeblich zum Krankheitsbild beiträgt. Hierzu gehören u. a. Fibrosen der Lunge, Leber und Haut (Skleroderma) sowie die Atherosklerose.Inhibitors of prolyl hydroxylase are therefore suitable substances in the Therapy of diseases in which the deposition of collagens is essential contributes to the clinical picture. These include a. Fibrosis of the lungs, liver and Skin (scleroderma) and atherosclerosis.

Es ist bekannt, daß das Enzym Prolinhydroxylase durch Pyridin-2,4- und -2,5- dicarbonsäure effektiv gehemmt wird (K. Majamaa et al., Eur. J. Biochem. 138 (1984) 239-245). Diese Verbindungen sind in der Zellkultur allerdings nur in sehr hohen Konzentrationen als Hemmstoffe wirksam (Tschank, G. et al., Biochem. J. 238 (1987) 625-633).It is known that the enzyme proline hydroxylase can be isolated by pyridine-2,4- and -2,5- dicarboxylic acid is effectively inhibited (K. Majamaa et al., Eur. J. Biochem. 138 (1984) 239-245). However, these compounds are only found in cell culture very high concentrations as inhibitors (Tschank, G. et al.,  Biochem. J. 238 (1987) 625-633).

Auch Prodrugs der Pyridin-2,4(5)-dicarboxylate sind bekannt. Diese sind in den älteren deutschen Anmeldungen P 42 33 124.2, P 42 38 506.7 und P 42 09 424.0 beschrieben.Prodrugs of the pyridine-2,4 (5) dicarboxylates are also known. These are in the older German applications P 42 33 124.2, P 42 38 506.7 and P 42 09 424.0.

N-Oxalylglycine als Inhibitoren der Prolyl-4-hydroxylase sind aus J. Med. Chem. 1992, 35, 2652-2658 (Cunliffe et al.), und EP-A-0 457 163 (Baader et al.) bekannt.N-oxalylglycines as inhibitors of prolyl-4-hydroxylase are known from J. Med. Chem. 1992, 35, 2652-2658 (Cunliffe et al.), And EP-A-0 457 163 (Baader et al.) known.

Hydroxyisochinoline- und Hydroxycinnolincarbonsäureglycylamide sind aus Biochem. Soc. Trans. 1991, 19, 812-815 (Franklin et al.) bekannt. 3-Benzyloxy­ pyridin-2-carbonsäure-L-threonylamid und 3-Benzyloxypyridin-2-carbonsäure- ((Fmoc-Phg)-L-threonyl)amid-Hydrochlorid sind aus Liebigs Anm. Chem., 1986, 1-20, Kessler et al. bekannt.Hydroxyisoquinoline and hydroxycinnoline carboxylic acid glycylamides are made Biochem. Soc. Trans. 1991, 19, 812-815 (Franklin et al.). 3-benzyloxy pyridine-2-carboxylic acid-L-threonylamide and 3-benzyloxypyridine-2-carboxylic acid- ((Fmoc-Phg) -L-threonyl) amide hydrochloride are from Liebigs Anm. Chem., 1986, 1-20, Kessler et al. known.

Überraschenderweise wurde nun gefunden, daß heterocyclische Carbonsäureamide mit einem Ether-, einem Thioether- oder einem Amino- Substituenten in ortho-Position zur Amidfunktion stark wirksame Inhibitoren der Prolyl-4-hydroxylase sind.Surprisingly, it has now been found that heterocyclic Carboxamides with an ether, a thioether or an amino Substituents in the ortho position to the amide function are potent inhibitors of Prolyl 4-hydroxylase.

Die erfindungsgemäßen Verbindungen entsprechen der allgemeinen Formel IThe compounds according to the invention correspond to the general formula I.

in welcher
Q O, S und NR′,
X O und S,
Y C-R³ oder N,
m 0 und 1,
A (C₁-C₄)-Alkylen, das gegebenenfalls substituiert ist mit einem oder zwei Substituenten aus der Reihe Halogen, Cyano, Nitro, Trifluormethyl, (C₁-C₆)-Alkyl, (C₁-C₆)-Hydroxyalkyl, (C₁-C₆)-Alkoxy, -O-[CH₂]x-CfH(2f+1-g)Halg, vorzugsweise (C₁-C₈)-Fluoralkoxy, (C₁-C₈)-Fluoralkenyloxy, (C₁-C₈)-Fluoralkinyloxy, -OCF₂Cl oder -O-CF₂-CHFCl, (C₁-C₆)-Alkylmercapto, (C₁-C₆)-Alkylsulfinyl, (C₁-C₆)-Alkylsulfonyl, (C₁-C₆)-Alkylcarbonyl, (C₁-C₆)-Alkoxycarbonyl, Carbamoyl, N-(C₁-C₄)- Alkylcarbamoyl, N, N-Di-(C₁-C₄)-alkylcarbamoyl, (C₁-C₆)-Alkylcarbonyloxy, (C₃-C₈)-Cycloalkyl, Phenyl, Benzyl, Phenoxy, Benzyloxy, Anilino, N-Methylanilino, Phenylmercapto, Phenylsulfonyl, Phenylsulfinyl, Sulfamoyl, N-(C₁-C₄)-Alkylsulfamoyl, N,N-Di-(C₁-C₄)-alkylsulfamoyl, oder
mit einem substituierten (C₆-C₁₂)-Aryloxy-, (C₇-C₁₁)-Aralkyloxy, (C₆-C₁₂)- Aryl- oder (C₇-C₁₁)-Aralkyl-Rest, der im Arylteil 1,2, 3, 4 oder 5 gleiche oder verschiedene Substituenten aus der Reihe Halogen, Cyano, Nitro, Trifluormethyl, (C₁-C₆)-Alkyl, (C₁-C₆)-Alkoxy, -O-[CH₂]x-CfH(2f+1-g)Halg, -OCF₂Cl,-O-CF₂-CHFCl, (C₁-C₆)-Alkylmercapto, (C₁-C₆)-Alkylsulfinyl, (C₁-C₆)-Alkylsulfonyl, (C₁-C₆)-Alkylcarbonyl, (C₁-C₆)-Alkoxycarbonyl, Carbamoyl, N-(C₁-C₄)-Alkylcarbamoyl, N,N-Di- (C₁-C₄)-alkylcarbamoyl, (C₁-C₆)-Alkylcarbonyloxy, (C₃-C₈)-Cycloalkyl, Sulfamoyl, N-(C₁-C₄)-Alkylsulfamoyl oder N,N-Di-(C₁-C₄)-alkylsulfamoyl trägt, oder
mit den Substituenten R⁵ des α-C-Atoms einer α-Aminosäure, wobei die natürlichen L-Aminosäuren und ihre D-Isomeren Verwendung finden können;
B eine saure Gruppierung aus der Reihe -CO₂H, -CONHCOR′′′, -CONHSOR′′′, CONHSO₂R′′′, -NHSO₂CF₃, Tetrazolyl, Imidazolyl oder 3- Hydroxyisoxazolyl bedeutet, wobei R′′′ Aryl, Heteroaryl, (C₃-C₇)- Cycloalkyl oder (C₁-C₄)-Alkyl, gegebenenfalls monosubstituiert mit (C₆- C₁₂)-Aryl, Heteroaryl, OH, SH, (C₁-C₄)-Alkyl, (C₁-C₄)-Alkoxy, (C₁-C₄)- Thioalkyl, -Sulfinyl oder -Sulfonyl, CF₃, Cl, Br, F, I, NO₂, -COOH, (C₂-C₅)- Alkoxycarbonyl, NH₂, Mono- oder Di-(C₁-C₄-alkylamino oder (C₁-C₄)- Perfluoroalkyl bedeutet,
R¹, R² und R³ gleich oder verschieden sind und Wasserstoff, Hydroxy, Halogen, Cyano, Trifluormethyl, Nitro, Carboxy, (C₁-C₁₂)-Alkyl, (C₃-C₈)- Cycloalkyl, (C₃-C₈)-Cycloalkyl-(C₁-C₁₂)-alkyl, (C₃-C₈)-Cycloalkoxy, (C₃-C₈)-Cycloalkyl-(C₁-C₁₂)-alkoxy, (C₃-C₈)-Cycloalkyloxy-(C₁-C₁₂)- alkyl, (C₃-C₈)-Cycloalkyloxy-(C₁-C₁₂)-alkoxy, (C₃-C₈)-Cycloalkyl- (C₁-C₈)-alkyl-(C₁-C₆)-alkoxy, (C₃-C₈)-Cycloalkyl-(C₁-C₈)-alkoxy-(C₁- C₆)-alkyl, (C₃-C₈)-Cycloalkyloxy-(C₁-C₈)-alkoxy-(C₁-C₆)-alkyl, (C₃- C₈)-Cycloalkoxy-(C₁-C₈)-alkoxy-(C₁-C₈)-alkoxy, (C₆-C₁₂)-Aryl, (C₇- C₁₆)-Aralkyl, (C₂-C₁₂)-Alkenyl, (C₂-C₁₂)-Alkinyl, (C₁-C₁₂)-Alkoxy, (C₁-C₁₂)-Alkoxy-(C₁-C₁₂)alkyl, (C₁-C₁₂)-Alkoxy-(C₁-C₁₂)alkoxy, (C₁-C₁₂)-Alkoxy-(C₁-C₈)-alkoxy-(C₁-C₈)-alkyl, (C₆-C₁₂)-Aryloxy, (C₇-C₁₆)-Aralkyloxy, (C₆-C₁₂)-Aryloxy-(C₁-C₆)-alkoxy, (C₇-C₁₆)- Aralkoxy-(C₁-C₆)-alkoxy, (C₁-C₈)-Hydroxyalkyl, (C₆-C₁₆)-Aryloxy- (C₁-C₈)-alkyl, (C₇-C₁₆)-Aralkoxy-(C₁-C₈)-alkyl, (C₆-C₁₂)-Aryloxy- (C₁-C₈)-alkoxy-(C₁-C₆)-alkyl, (C₇-C₁₂)-Aralkyloxy-(C₁-C₈)-alkoxy- (C₁-C₆)-alkyl, O-[CH2-]xCfH(2f+1-g)Fg,-OCF₂Cl, -OCF₂-CHFCl,
(C₁-C₁₂)-Alkylcarbonyl, (C₃-C₈)-Cycloalkylcarbonyl, (C₆-C₁₂)- Arylcarbonyl, (C₇-C₁₆)-Aralkylcarbonyl, Cinnamoyl, (C₂-C₁₂) Alkenylcarbonyl, (C₂-C₁₂)-Alkinylcarbonyl,
(C₁-C₁₂)-Alkoxycarbonyl, (C₁-C₁₂)-Alkoxy-(C₁-C₁₂)-alkoxycarbonyl, (C₆-C₁₂)-Aryloxycarbonyl, (C₇-C₁₆)-Aralkoxycarbonyl, (C₃-C₁₀)- Cycloalkoxycarbonyl, (C₂-C₁₂)-Alkenyloxycarbonyl, (C₂-C₁₂)- Alkinyloxycarbonyl,
(C₁-C₁₂)-Alkylcarbonyloxy, (C₃-C₈)-Cycloalkylcarbonyloxy, (C₆-C₁₂)-Arylcarbonyloxy, (C₇-C₁₆)-Aralkylcarbonyloxy, Cinnamoyloxy, (C₂-C₁₂)-Alkenylcarbonyloxy, (C₂-C₁₂)- Alkinylcarbonyloxy,
(C₁-C₁₂)-Alkoxycarbonyloxy, (C₁-C₁₂)-Alkoxy-(C₁-C₁₂)- alkoxycarbonyloxy, (C₆-C₁₂)-Aryloxycarbonyloxy, (C₇-C₁₆)- Aralkyloxycarbonyloxy, (C₃-C₈)-Cycloalkoxycarbonyloxy, (C₂-C₁₂)- Alkenyloxycarbonyloxy, (C₂-C₁₂)-Alkinyloxycarbonyloxy,
Carbamoyl, N-(C₁-C₁₂)-Alkylcarbamoyl, N,N-Di-(C₁-C₁₂)- alkylcarbamoyl, N-(C₃-C₈)-Cycloalkylcarbamoyl, N,N-Dicyclo (C₃-C₈)-alkylcarbamoyl, N-(C₁-C₁₀)-Alkyl-N-(C₃-C₈)- Cycloalkylcarbamoyl, N-((C₃-C₈)-Cycloalkyl-(C₁-C₆)- alkyl)carbamoyl, N-(C₁-C₆)-Alkyl-N-((C₃-C₈-Cycloalkyl-(C₁-C₆)- alkyl)carbamoyl, N-(+)-Dehydroabietylcarbamoyl, N-(C₁-C₆)-Alkyl- N-Dehydroabietylcarbamoyl, N-(C₆-C₁₂)-Arylcarbamoyl, N-(C₇-C₁₆)- Aralkylcarbamoyl, N-(C₁-C₁₀)-Alkyl-N-(C₆-C₁₆)arylcarbamoyl, N- (C₁-C₁₀)-Alkyl-N-(C₇-C₁₆)-Aralkylcarbamoyl, N-((C₁-C₁₀)-Alkoxy- (C₁-C₁₀)alkyl)carbamoyl, N-((C₆-C₁₆)-Aryloxy-(C₁- C₁₀)alkyl)carbamoyl,
N-((C₇-C₁₆)-Aralkyloxy-(C₁-C₁₀)alkyl)carbamoyl, N-(C₁-C₁₀)-Alkyl-N-((C₁-C₁₀)-Alkoxy-(C₁-C₁₀)alkyl)carbamoyl, N-(C₁-C₁₀)-Alkyl-N-((C₆-C₁₂)-Aryloxy-(C₁-C₁₀)alkyl)carbamoyl, N-(C₁-C₁₀)-Alkyl-N-((C₇-C₁₆)Aralkyloxy-(C₁-C₁₀)alkyl)carbamoyl, CON(CH₂)h, worin eine CH₂-Gruppe durch O, S, N-(C₁- C₈)Alkylimino, N-(C₃-C₈)-Cycloalkylimino, N-(C₃-C₈)-Cycloalkyl-(C₁- C₄)alkylimino, N-(C₆-C₁₂)-Arylimino, N-(C₇-C₁₆)-Aralkylimino oder N-(C₁-C₄)-Alkoxy-(C₁-C₆)-alkylimino ersetzt sein kann und h 3 bis 7 bedeutet,
Carbamoyloxy, N-(C₁-C₁₂)-Alkylcarbamoyloxy, N,N-Di- (C₁-C₁₂)-alkylcarbamoyloxy, N-(C₃-C₈)-Cycloalkylcarbamoyloxy, N-(C₆-C₁₂)-Arylcarbamoyloxy, N-(C₇-C₁₆)-Aralkylcarbamoyloxy, N-(C₁-C₁₀)-Alkyl-N-(C₆-C₁₂)arylcarbamoyloxy, N-(C₁-C₁₀)-Alkyl-N- (C₇-C₁₆)-Aralkylcarbamoyloxy, N-((C₁-C₁₀)alkyl))carbamoyloxy, N-((C₆-C₁₂)-Aryloxy-(C₁-C₁₀)alkyl))carbamoyloxy, N-((C₇-C₁₆)-Aralkyloxy-(C₁-C₁₀)alkyl)carbamoyloxy, N-(C₁-C₁₀)-Alkyl-N-((C₁-C₁₀)-Alkoxy-(C₁-C₁₀)alkyl)carbamoyloxy, N-(C₁-C₁₀)-Alkyl-N-((C₆-C₁₂)-Aryloxy-(C₁-C₁₀)alkyl)carbamoyloxy, N-(C₁-C₁₀)-Alkyl-N-((C₇-C₁₆)-Aralkyloxy- (C₁-C₁₀)alkyl)carbamoyloxy,
Amino, (C₁-C₁₂)-Alkylamino, Di-(C₁-C₁₂)alkylamino, (C₃-C₈)- Cycloalkylamino, (C₃-C₁₂)-Alkenylamino, (C₃-C₁₂)-Alkinylamino, N-(C₆-C₁₂)-Arylamino, N-(C₇-C₁₁)-Aralkylamino, N-Alkyl- Aralkylamino, N-Alkyl-Arylamino, (C₁-C₁₂)-Alkoxyamino, (C₁-C₁₂)- Alkoxy-N-(C₁-C₁₀)-alkylamino,
(C₁-C₁₂)-Alkanoylamino, (C₃-C₈)-Cycloalkanoylamino, (C₆-C₁₂)- Aroylamino, (C₇-C₁₆)-Aralkanoylamino, (C₁-C₁₂)-Alkanoyl-N- (C₁-C₁₀)-alkylamino, (C₃-C₈)-Cycloalkanoyl-N-(C₁-C₁₀)-alkylamino, (C₆-C₁₂)-Aroyl-N-(C₁-C₁₀)alkylamino, (C₇-C₁₁)-Aralkanoyl-N- (C₁-C₁₀)-alkylamino,
(C₁-C₁₂)-Alkanoylamino-(C₁-C₈)-alkyl, (C₃-C₈)-Cycloalkanoylamino- (C₁-C₈)alkyl, (C₆-C₁₂)-Aroylamino-(C₁-C₈)-alkyl, (C₇-C₁₆)- Aralkanoylamino-(C₁-C₈)-alkyl, Amino (C₁-C₁₀) alkyl, N-(C₁-C₁₀)alkylamino-(C₁-C₁₀)alkyl, N,N-Di-(C₁-C₁₀)alkylamino (C₁- C₁₀)alkyl, (C₃-C₈)cycloalkylamino-(C₁-C₁₀)alkyl, (C₁-C₁₂)-Alkylmercapto, (C₁-C₁₂)-Alkylsulfinyl, (C₁-C₁₂)- Alkylsulfonyl, (C₆-C₁₂)-Arylmercapto, (C₆-C₁₂)-Arylsulfinyl, (C₆-C₁₂)-Arylsulfonyl, (C₇-C₁₆)-Aralkylmercapto, (C₇-C₁₆)- Aralkylsulfinyl, (C₇-C₁₆)-Aralkylsulfonyl,
Sulfamoyl, N-(C₁-C₁₀)-Alkylsulfamoyl, N,N-Di-(C₁-C₁₀)- alkylsulfamoyl, (C₃-C₈-cycloalkylsulfamoyl, N-(C₆-(C₁₂)-Arylsulfamoyl, N-(C₇-C₁₆)-Aralkylsulfamoyl, N-(C₁-C₁₀)-Alkyl-N-(C₆-C₁₂)-Arylsulfamoyl, N-(C₁-C₁₀)-Alkyl-N-(C₇-C₁₆)-Aralkylsulfamoyl, (C₁-C₁₀)-Alkyl-sulfonamido, N-((C₁-C₁₀)alkyl)-(C₁-C₁₀)alkylsulfonamido, (C₇-C₁₆)- Aralkylsulfonamido, N-((C₁-C₁₀)alkyl-(C₇-C₁₆)-Aralkylsulfonamido, bedeuten,
wobei die Reste, die einen Arylrest enthalten ihrerseits am Aryl substituiert sein können durch 1 bis 5 gleiche oder verschiedene Reste aus der Reihe:
Hydroxy, Halogen, Cyano, Trifluormethyl, Nitro, Carboxy, (C₁-C₁₂)- Alkyl, (C₃-C₈)-Cycloalkyl, (C₆-C₁₂)-Aryl, (C₇-C₁₆)-Aralkyl, (C₁ -C₁₂)- Alkoxy, (C₁-C₁₂)-Alkoxy-(C₁-C₁₂)alkyl, (C₁-C₁₂)-Alkoxy- (C₁-C₁₂)alkoxy, (C₆-C₁₂)-Aryloxy, (C₇-C₁₆)-Aralkyloxy, (C₁-C₈)- Hydroxyalkoyl,
(C₁-C₁₂)-Alkylcarbonyl, (C₃-C₈)-Cycloalkylcarbonyl, (C₆-C₁₂)- Arylcarbonyl, (C₇-C₁₆)-Aralkylcarbonyl,
(C₁-C₁₂)-Alkoxycarbonyl, (C₁-C₁₂)-Alkoxy-(C₁-C₁₂)-alkoxycarbonyl, (C₆-C₁₂)-Aryloxycarbonyl, (C₇-C₁₆)-Aralkoxycarbonyl, (C₃-C₈)- Cycloalkoxycarbonyl, (C₂-C₁₂)-Alkenyloxycarbonyl, (C₂-C₁₂)- Alkinyloxycarbonyl,
(C₁-C₁₂)-Alkylcarbonyloxy, (C₃-C₈)-Cycloalkylcarbonyloxy, (C₆-C₁₂)-Arylcarbonyloxy, (C₇-C₁₆)-Arylkylcarbonyloxy,
Cinnamoyloxy, (C₂-C₁₂)-Alkenylcarbonyloxy, (C₂-C₁₂)- Alkinylcarbonyloxy,
(C₁-C₁₂)-Alkoxycarbonyloxy, (C₁-C₁₂)-Alkoxy-(C₁-C₁₂)- alkoxycarbonyloxy, (C₆-C₁₂)-Aryloxycarbonyloxy, (C₇-C₁₆)- Aralkyloxycarbonyloxy, (C₃-C₈)-Cycloalkoxycarbonyloxy, (C₂-C₁₂)- Alkenyloxycarbonyloxy, (C₂-C₁₂)-Alkinyloxycarbonyloxy,
Carbamoyl, N-(C₁-C₁₂)-Alkylcarbamoyl, N,N-Di-(C₁-C₁₂)- alkylcarbamoyl, N-(C₃-C₈)-Cycloalkylcarbamoyl, N,N-Dicyclo (C₃-C₈)-alkylcarbamoyl, N-(C₁-C₁₀)-Alkyl-N-(C₃-C₈)- Cycloalkylcarbamoyl, N-((C₃-C₈)-Cycloalkyl-(C₁-C₆)- alkyl)carbamoyl, N-(C₁-C₆)-Alkyl-N-((C₃-C₈-Cycloalkyl-(C₁-C₆)- alkyl)carbamoyl, N-(+)-Dehydroabietylcarbamoyl, N-(C₁-C₆)-Alkyl- N-Dehydroabietylcarbamoyl, N-(C₆-C₁₂)-Arylcarbamoyl, N-(C₇-C₁₆)- Aralkylcarbamoyl, N-(C₁-C₁₀)-Alkyl-N-(C₆-C₁₆)arylcarbamoyl, N- (C₁-C₁₀)-Alkyl-N-(C₇-C₁₆)-Aralkylcarbamoyl, N-((C₁-C₁₀)-Alkoxy- (C₁-C₁₀)alkyl)carbamoyl, N-((C₆-C₁₆)-Aryloxy-(C₁- C₁₀)alkyl)carbamoyl,
N-((C₇-C₁₆)-Aralkyloxy-(C₁-C₁₀)alkyl)carbamoyl, N-(C₁-C₁₀)-Alkyl-N-((C₁-C₁₀)-Alkoxy-(C₁-C₁₀)alkyl)carbamoyl, N-(C₁-C₁₀)-Alkyl-N-((C₆-C₁₂)-Aryloxy-(C₁-C₁₀)alkyl)carbamoyl, N-(C₁-C₁₀)-Alkyl-N-((C₇-C₁₆)Aralkyloxy-(C₁-C₁₀)alkyl)carbamoyl, CON(CH₂)h worin eine CH₂-Gruppe durch O, S, N-(C₁- C₈)Alkylimino, N-(C₃-C₈)-Cycloalkylimino, N-(C₃-C₈)-Cycloalkyl-(C₁- C₄)alkylimino, N-(C₆-C₁₂)-Arylimino, N-(C₇-C₁₆)-Aralkylimino oder N-(C₁-C₄)-Alkoxy (C₁-C₆)-alkylimino ersetzt ein kann und h 3 bis 7 bedeutet,
Carbamoyloxy, N-(C₁-C₁₂)-Alkylcarbamoyloxy, N,N-Di-(C₁-C₁₂)- alkylcarbamoyloxy, N-(C₃-C₈)-Cycloalkylcarbamoyloxy, N-(C₆-C₁₆)- Arylcarbamoyloxy, N-(C₇-C₁₆)-Aralkylcarbamoyloxy, N-(C₁-C₁₀)-
Alkyl-N-(C₆-C₁₂)arylcarbamoyloxy, N-(C₁-C₁₀)-Alkyl-N-(C₇-C₁₆)- Aralkylcarbamoyloxy, N-((C₁-C₁₀)alkyl))carbamoyloxy, N-((C₆-C₁₂)-Aryloxy-(C₁-C₁₀)alkyl)carbamoyloxy, N-((C₇-C₁₆)-Aralkyloxy-(C₁-C₁₀)alkyl)carbamoyloxy, N-(C₁-C₁₀)-Alkyl-N-((C₁-C₁₀)-Alkoxy-(C₁-C₁₀)alkyl)carbamoyloxy, N-(C₁-C₁₀)-Alkyl-N-((C₆-C₁₂)-Aryloxy-(C₁-C₁₀)alkyl)carbamoyloxy, N-(C₁-C₁₀)-Alkyl-N-((C₇-C₁₆)-Aralkyloxy- (C₁-C₁₀)alkyl)carbamoyloxy,
Amino, (C₁-C₁₂)-Alkylamino, Di-(C₁-C₁₂)alkylamino, (C₃-C₈)- Cycloalkylamino, (C₃-C₁₂)-Alkenylamino, (C₃-C₁₂)-Alkinylamino, N- (C₆-C₁₂)-Arylamino, N-(C₇-C₁₁)-Aralkylamino, N-Alkyl- Aralkylamino, N-Alkyl-Arylamino, (C₁-C₁₂)-Alkoxyamino, (C₁-C₁₂)- Alkoxy-N-(C₁-C₁₀)-alkylamino,
(C₁-C₁₂)-Alkanoylamino, (C₃-C₈)-Cycloalkanoylamino, (C₆-C₁₂)-Aroylamino, (C₇-C₁₆)-Aralkanoylamino, (C₁-C₁₂)-Alkanoyl- N-(C₁-C₁₀)-alkylamino, (C₃-C₈)-Cycloalkanoyl-N-(C₁-C₁₀)- alkylamino, (C₆-C₁₂)-Aroyl-N-(C₁-C₁₀)alkylamino, (C₇-C₁₁)- Aralkanoyl-N-(C₁-C₁₀)-alkylamino,
(C₁-C₁₂)-Alkanoylamino-(C₁-C₈)-alkyl, (C₃-C₈)-Cycloalkanoylamino- (C₁-C₈)alkyl, (C₆-C₁₂)-Aroylamino- (C₁-C₈)-alkyl, (C₇-C₁₆)-Aralkanoylamino-(C₁-C₈)-alkyl, Amino- (C₁-C₁₀)-alkyl, N-(C₁-C₁₀)alkylamino-(C₁-C₁₀)alkyl, N,N-Di (C₁-C₁₀)alkylamino-(C₁-C₁₀)alkyl, (C₃-C₈)Cycloalkylamino-(C₁- C₁₀)alkyl,
(C₁-C₁₂)-Alkylmercapto, (C₁-C₁₂)-Alkylsulfinyl, (C₁-C₁₂)- Alkylsulfonyl, (C₆-C₁₆)-Arylmercapto, (C₆-C₁₆)-Arylsulfinyl, (C₆- C₁₆)-Arylsulfonyl, (C₇-C₁₆)-Aralkylmercapto, (C₇-C₁₆)- Aralkylsulfinyl, (C₇-C₁₆)-Aralkylsulfonyl,
R¹ und R² oder R² und R³ können eine Kette [CH₂]o bilden, in welcher eine oder zwei CH₂-Gruppen der gesättigten oder mit einer C=C-Doppelbindung ungesättigten Kette gegebenenfalls durch O, S, SO, SO₂ oder NR′ ersetzt sind, o = 3, 4 oder 5 bedeutet und
R′ Wasserstoff, (C₆-C₁₂)-Aryl, (C₁-C₈)-Alkyl, (C₁-C₈)-Alkoxy-(C₁-C₈)alkyl, (C₇-C₁₂)-Aralkoxy-(C₁-C₈)alkyl, (C₆-C₁₂)-Aryloxy-(C₁-C₈)-alkyl, (C₁-C₁₀)- Alkanoyl, ggf. substituiertes (C₇-C₁₆)-Aralkanoyl, ggf. substituiertes (C₆-C₁₂)-Aroyl bedeuten.in which
QO, S and NR ′,
XO and S,
Y C-R³ or N,
m 0 and 1,
A (C₁-C₄) alkylene, which is optionally substituted with one or two substituents from the series halogen, cyano, nitro, trifluoromethyl, (C₁-C₆) alkyl, (C₁-C₆) hydroxyalkyl, (C₁-C₆) -Alkoxy, -O- [CH₂] x -C f H (2f + 1-g) Hal g , preferably (C₁-C₈) fluoroalkoxy, (C₁-C₈) fluoroalkenyloxy, (C₁-C₈) fluoroalkynyloxy, - OCF₂Cl or -O-CF₂-CHFCl, (C₁-C₆) alkyl mercapto, (C₁-C₆) alkylsulfinyl, (C₁-C₆) alkylsulfonyl, (C₁-C₆) alkylcarbonyl, (C₁-C₆) alkoxycarbonyl, carbamoyl , N- (C₁-C₄) alkylcarbamoyl, N, N-di- (C₁-C₄) alkylcarbamoyl, (C₁-C₆) alkylcarbonyloxy, (C₃-C₈) cycloalkyl, phenyl, benzyl, phenoxy, benzyloxy, anilino , N-methylanilino, phenylmercapto, phenylsulfonyl, phenylsulfinyl, sulfamoyl, N- (C₁-C₄) alkylsulfamoyl, N, N-di- (C₁-C₄) alkylsulfamoyl, or
with a substituted (C₆-C₁₂) aryloxy, (C₇-C₁₁) aralkyloxy, (C₆-C₁₂) aryl or (C₇-C₁₁) aralkyl radical which is in the aryl part 1,2, 3, 4 or 5 identical or different substituents from the series halogen, cyano, nitro, trifluoromethyl, (C₁-C₆) alkyl, (C₁-C₆) alkoxy, -O- [CH₂] x -C f H (2f + 1-g) Hal g , -OCF₂Cl, -O-CF₂-CHFCl, (C₁-C₆) alkyl mercapto, (C₁-C₆) alkylsulfinyl, (C₁-C₆) alkylsulfonyl, (C₁-C₆) alkylcarbonyl, (C₁-C₆) -Alkoxycarbonyl, carbamoyl, N- (C₁-C₄) alkylcarbamoyl, N, N-di- (C₁-C₄) alkylcarbamoyl, (C₁-C₆) alkylcarbonyloxy, (C₃-C₈) cycloalkyl, sulfamoyl, N- ( C₁-C₄) alkylsulfamoyl or N, N-di- (C₁-C₄) alkylsulfamoyl, or
with the substituents R⁵ of the α-C atom of an α-amino acid, whereby the natural L-amino acids and their D-isomers can be used;
B is an acidic group from the series -CO₂H, -CONHCOR ''',-CONHSOR''', CONHSO₂R ''', -NHSO₂CF₃, tetrazolyl, imidazolyl or 3-hydroxyisoxazolyl, where R''' aryl, heteroaryl, (C₃ -C₇) - cycloalkyl or (C₁-C₄) alkyl, optionally monosubstituted with (C₆- C₁₂) aryl, heteroaryl, OH, SH, (C₁-C₄) alkyl, (C₁-C₄) alkoxy, (C₁- C₄) - Thioalkyl, sulfinyl or sulfonyl, CF₃, Cl, Br, F, I, NO₂, -COOH, (C₂-C₅) - alkoxycarbonyl, NH₂, mono- or di- (C₁-C₄-alkylamino or (C₁ -C₄) - Perfluoroalkyl means
R¹, R² and R³ are the same or different and are hydrogen, hydroxy, halogen, cyano, trifluoromethyl, nitro, carboxy, (C₁-C₁₂) alkyl, (C₃-C₈) cycloalkyl, (C₃-C₈) cycloalkyl- (C₁ -C₁₂) alkyl, (C₃-C₈) cycloalkoxy, (C₃-C₈) cycloalkyl- (C₁-C₁₂) alkoxy, (C₃-C₈) cycloalkyloxy- (C₁-C₁₂) alkyl, (C₃-C₈ ) -Cycloalkyloxy- (C₁-C₁₂) -alkoxy, (C₃-C₈) -cycloalkyl- (C₁-C₈) -alkyl- (C₁-C₆) -alkoxy, (C₃-C₈) -cycloalkyl- (C₁-C₈) - alkoxy- (C₁- C₆) alkyl, (C₃-C₈) cycloalkyloxy- (C₁-C₈) alkoxy- (C₁-C₆) alkyl, (C₃- C₈) cycloalkoxy- (C₁-C₈) alkoxy- (C₁-C₈) alkoxy, (C₆-C₁₂) aryl, (C₇- C₁₆) aralkyl, (C₂-C₁₂) alkenyl, (C₂-C₁₂) alkynyl, (C₁-C₁₂) alkoxy, (C₁ -C₁₂) alkoxy- (C₁-C₁₂) alkyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxy, (C₁-C₁₂) alkoxy- (C₁-C₈) alkoxy- (C₁-C₈) - alkyl, (C₆-C₁₂) aryloxy, (C₇-C₁₆) aralkyloxy, (C₆-C₁₂) aryloxy- (C₁-C₆) alkoxy, (C₇-C ₆) - Aralkoxy- (C₁-C₆) alkoxy, (C₁-C₈) hydroxyalkyl, (C₆-C₁₆) aryloxy- (C₁-C₈) alkyl, (C₇-C₁₆) aralkoxy- (C₁-C₈) -alkyl, (C₆-C₁₂) aryloxy- (C₁-C₈) alkoxy- (C₁-C₆) alkyl, (C₇-C₁₂) aralkyloxy- (C₁-C₈) alkoxy- (C₁-C₆) alkyl , O- [CH 2- ] x C f H (2f + 1-g) F g , -OCF₂Cl, -OCF₂-CHFCl,
(C₁-C₁₂) alkylcarbonyl, (C₃-C₈) cycloalkylcarbonyl, (C₆-C₁₂) arylcarbonyl, (C₇-C₁₆) aralkylcarbonyl, cinnamoyl, (C₂-C₁₂) alkenylcarbonyl, (C₂-C₁₂) alkynylcarbonyl,
(C₁-C₁₂) alkoxycarbonyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyl, (C₆-C₁₂) aryloxycarbonyl, (C₇-C₁₆) aralkoxycarbonyl, (C₃-C₁₀) - cycloalkoxycarbonyl, (C₂ -C₁₂) alkenyloxycarbonyl, (C₂-C₁₂) alkynyloxycarbonyl,
(C₁-C₁₂) alkylcarbonyloxy, (C₃-C₈) cycloalkylcarbonyloxy, (C₆-C₁₂) arylcarbonyloxy, (C₇-C₁₆) aralkylcarbonyloxy, cinnamoyloxy, (C₂-C₁₂) alkenylcarbonyloxy, (C₂-C₁₂), alkynylcarbonyloxy
(C₁-C₁₂) alkoxycarbonyloxy, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyloxy, (C₆-C₁₂) aryloxycarbonyloxy, (C₇-C₁₆) aralkyloxycarbonyloxy, (C₃-C₈) cycloalkoxycarbonyloxy, (C₂ -C₁₂) - alkenyloxycarbonyloxy, (C₂-C₁₂) alkynyloxycarbonyloxy,
Carbamoyl, N- (C₁-C₁₂) alkylcarbamoyl, N, N-di- (C₁-C₁₂) alkylcarbamoyl, N- (C₃-C₈) -cycloalkylcarbamoyl, N, N-dicyclo (C₃-C₈) -alkylcarbamoyl, N - (C₁-C₁₀) alkyl-N- (C₃-C₈) - cycloalkylcarbamoyl, N - ((C₃-C₈) cycloalkyl- (C₁-C₆) - alkyl) carbamoyl, N- (C₁-C₆) alkyl- N - ((C₃-C₈-cycloalkyl- (C₁-C₆) - alkyl) carbamoyl, N - (+) - dehydroabietylcarbamoyl, N- (C₁-C₆) alkyl- N-dehydroabietylcarbamoyl, N- (C₆-C₁₂) - Arylcarbamoyl, N- (C₇-C₁₆) aralkylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₆) arylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₇-C₁₆) aralkylcarbamoyl , N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N - ((C₆-C₁₆) aryloxy- (C₁- C₁₀) alkyl) carbamoyl,
N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyl, CON (CH₂) h , wherein a CH₂ group by O, S, N- (C₁- C₈) alkylimino, N- (C₃-C₈) cycloalkylimino, N- (C₃-C₈ ) -Cycloalkyl- (C₁- C₄) alkylimino, N- (C₆-C₁₂) arylimino, N- (C₇-C₁₆) aralkylimino or N- (C₁-C₄) alkoxy- (C₁-C₆) alkylimino can and h means 3 to 7,
Carbamoyloxy, N- (C₁-C₁₂) alkylcarbamoyloxy, N, N-Di- (C₁-C₁₂) alkylcarbamoyloxy, N- (C₃-C₈) cycloalkylcarbamoyloxy, N- (C₆-C₁₂) arylcarbamoyloxy, N- (C₇ -C₁₆) aralkylcarbamoyloxy, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₂) arylcarbamoyloxy, N- (C₁-C₁₀) alkyl-N- (C₇-C₁₆) aralkylcarbamoyloxy, N - ((C₁ -C₁₀) alkyl)) carbamoyloxy, N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀) alkyl)) carbamoyloxy, N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyloxy, N - (C₁-C₁₀) alkyl-N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyloxy,
Amino, (C₁-C₁₂) alkylamino, di- (C₁-C₁₂) alkylamino, (C₃-C₈) cycloalkylamino, (C₃-C₁₂) alkenylamino, (C₃-C₁₂) alkynylamino, N- (C₆-C₁₂) -Arylamino, N- (C₇-C₁₁) aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C₁-C₁₂) alkoxyamino, (C₁-C₁₂) - alkoxy-N- (C₁-C₁₀) alkylamino ,
(C₁-C₁₂) alkanoylamino, (C₃-C₈) cycloalkanoylamino, (C₆-C₁₂) aroylamino, (C₇-C₁₆) aralkanoylamino, (C₁-C₁₂) alkanoyl-N- (C₁-C₁₀) alkylamino, (C₃-C₈) cycloalkanoyl-N- (C₁-C₁₀) alkylamino, (C₆-C₁₂) aroyl-N- (C₁-C₁₀) alkylamino, (C₇-C₁₁) aralkanoyl-N- (C₁-C₁₀) -alkylamino,
(C₁-C₁₂) alkanoylamino- (C₁-C₈) alkyl, (C₃-C₈) -cycloalkanoylamino- (C₁-C₈) alkyl, (C₆-C₁₂) aroylamino- (C₁-C₈) alkyl, (C₇- C₁₆) - aralkanoylamino- (C₁-C₈) alkyl, amino (C₁-C₁₀) alkyl, N- (C₁-C₁₀) alkylamino- (C₁-C₁₀) alkyl, N, N-di- (C₁-C₁₀) alkylamino ( C₁- C₁₀) alkyl, (C₃-C₈) cycloalkylamino- (C₁-C₁₀) alkyl, (C₁-C₁₂) alkylmercapto, (C₁-C₁₂) alkylsulfinyl, (C₁-C₁₂) alkylsulfonyl, (C₆-C₁₂) - Arylmercapto, (C₆-C₁₂) arylsulfinyl, (C₆-C₁₂) arylsulfonyl, (C₇-C₁₆) aralkylmercapto, (C₇-C₁₆) aralkylsulfinyl, (C₇-C₁₆) aralkylsulfonyl,
Sulfamoyl, N- (C₁-C₁₀) alkylsulfamoyl, N, N-di- (C₁-C₁₀) alkylsulfamoyl, (C₃-C₈-cycloalkylsulfamoyl, N- (C₆- (C₁₂) arylsulfamoyl, N- (C₇-C₁₆ ) Aralkylsulfamoyl, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₂) arylsulfamoyl, N- (C₁-C₁₀) alkyl-N- (C₇-C₁₆) aralkylsulfamoyl, (C₁-C₁₀) - Alkylsulfonamido, N - ((C₁-C₁₀) alkyl) - (C₁-C₁₀) alkylsulfonamido, (C₇-C₁₆) aralkylsulfonamido, N - ((C₁-C₁₀) alkyl- (C₇-C₁₆) aralkylsulfonamido,
where the radicals which contain an aryl radical in turn can be substituted on the aryl by 1 to 5 identical or different radicals from the series:
Hydroxy, halogen, cyano, trifluoromethyl, nitro, carboxy, (C₁-C₁₂) alkyl, (C₃-C₈) cycloalkyl, (C₆-C₁₂) aryl, (C₇-C₁₆) aralkyl, (C₁ -C₁₂) - Alkoxy, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxy, (C₆-C₁₂) aryloxy, (C₇-C₁₆) aralkyloxy, (C₁ -C₈) - hydroxyalkoyl,
(C₁-C₁₂) alkylcarbonyl, (C₃-C₈) cycloalkylcarbonyl, (C₆-C₁₂) arylcarbonyl, (C₇-C₁₆) aralkylcarbonyl,
(C₁-C₁₂) alkoxycarbonyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyl, (C₆-C₁₂) aryloxycarbonyl, (C₇-C₁₆) aralkoxycarbonyl, (C₃-C₈) - cycloalkoxycarbonyl, (C₂ -C₁₂) alkenyloxycarbonyl, (C₂-C₁₂) alkynyloxycarbonyl,
(C₁-C₁₂) alkylcarbonyloxy, (C₃-C₈) cycloalkylcarbonyloxy, (C₆-C₁₂) arylcarbonyloxy, (C₇-C₁₆) arylkylcarbonyloxy,
Cinnamoyloxy, (C₂-C₁₂) alkenylcarbonyloxy, (C₂-C₁₂) alkynylcarbonyloxy,
(C₁-C₁₂) alkoxycarbonyloxy, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyloxy, (C₆-C₁₂) aryloxycarbonyloxy, (C₇-C₁₆) aralkyloxycarbonyloxy, (C₃-C₈) cycloalkoxycarbonyloxy, (C₂ -C₁₂) - alkenyloxycarbonyloxy, (C₂-C₁₂) alkynyloxycarbonyloxy,
Carbamoyl, N- (C₁-C₁₂) alkylcarbamoyl, N, N-di- (C₁-C₁₂) alkylcarbamoyl, N- (C₃-C₈) -cycloalkylcarbamoyl, N, N-dicyclo (C₃-C₈) -alkylcarbamoyl, N - (C₁-C₁₀) alkyl-N- (C₃-C₈) - cycloalkylcarbamoyl, N - ((C₃-C₈) cycloalkyl- (C₁-C₆) - alkyl) carbamoyl, N- (C₁-C₆) alkyl- N - ((C₃-C₈-cycloalkyl- (C₁-C₆) - alkyl) carbamoyl, N - (+) - dehydroabietylcarbamoyl, N- (C₁-C₆) alkyl- N-dehydroabietylcarbamoyl, N- (C₆-C₁₂) - Arylcarbamoyl, N- (C₇-C₁₆) aralkylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₆) arylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₇-C₁₆) aralkylcarbamoyl , N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N - ((C₆-C₁₆) aryloxy- (C₁- C₁₀) alkyl) carbamoyl,
N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyl, CON (CH₂) h wherein a CH₂ group is represented by O, S, N- (C₁- C₈) alkylimino, N- (C₃-C₈) cycloalkylimino, N- (C₃-C₈) -Cycloalkyl- (C₁- C₄) alkylimino, N- (C₆-C₁₂) arylimino, N- (C₇-C₁₆) aralkylimino or N- (C₁-C₄) alkoxy (C₁-C₆) alkylimino can be replaced and h means 3 to 7,
Carbamoyloxy, N- (C₁-C₁₂) alkylcarbamoyloxy, N, N-Di- (C₁-C₁₂) alkylcarbamoyloxy, N- (C₃-C₈) cycloalkylcarbamoyloxy, N- (C₆-C₁₆) arylcarbamoyloxy, N- (C₇ -C₁₆) aralkylcarbamoyloxy, N- (C₁-C₁₀) -
Alkyl-N- (C₆-C₁₂) arylcarbamoyloxy, N- (C₁-C₁₀) alkyl-N- (C₇-C₁₆) aralkylcarbamoyloxy, N - ((C₁-C₁₀) alkyl)) carbamoyloxy, N - ((C₆- C₁₂) aryloxy- (C₁-C₁₀) alkyl) carbamoyloxy, N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₁- C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀ ) -Alkyl-N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyloxy,
Amino, (C₁-C₁₂) alkylamino, di- (C₁-C₁₂) alkylamino, (C₃-C₈) cycloalkylamino, (C₃-C₁₂) alkenylamino, (C₃-C₁₂) alkynylamino, N- (C₆-C₁₂) -Arylamino, N- (C₇-C₁₁) aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C₁-C₁₂) alkoxyamino, (C₁-C₁₂) - alkoxy-N- (C₁-C₁₀) alkylamino ,
(C₁-C₁₂) alkanoylamino, (C₃-C₈) cycloalkanoylamino, (C₆-C₁₂) aroylamino, (C₇-C₁₆) aralkanoylamino, (C₁-C₁₂) alkanoyl-N- (C₁-C₁₀) alkylamino, (C₃-C₈) cycloalkanoyl-N- (C₁-C₁₀) alkylamino, (C₆-C₁₂) aroyl-N- (C₁-C₁₀) alkylamino, (C₇-C₁₁) - aralkanoyl-N- (C₁-C₁₀) -alkylamino,
(C₁-C₁₂) alkanoylamino- (C₁-C₈) alkyl, (C₃-C₈) -cycloalkanoylamino- (C₁-C₈) alkyl, (C₆-C₁₂) aroylamino- (C₁-C₈) alkyl, (C₇- C₁₆) aralkanoylamino- (C₁-C₈) alkyl, amino- (C₁-C₁₀) alkyl, N- (C₁-C₁₀) alkylamino- (C₁-C₁₀) alkyl, N, N-di (C₁-C₁₀) alkylamino - (C₁-C₁₀) alkyl, (C₃-C₈) cycloalkylamino- (C₁- C₁₀) alkyl,
(C₁-C₁₂) alkylmercapto, (C₁-C₁₂) alkylsulfinyl, (C₁-C₁₂) alkylsulfonyl, (C₆-C₁₆) arylmercapto, (C₆-C₁₆) arylsulfinyl, (C₆- C₁₆) arylsulfonyl, (C₇ -C₁₆) aralkylmercapto, (C₇-C₁₆) aralkylsulfinyl, (C₇-C₁₆) aralkylsulfonyl,
R¹ and R² or R² and R³ can form a chain [CH₂] o in which one or two CH₂ groups of the saturated or unsaturated chain with a C = C double bond are optionally replaced by O, S, SO, SO₂ or NR ' , o = 3, 4 or 5 and
R ′ is hydrogen, (C₆-C₁₂) aryl, (C₁-C₈) alkyl, (C₁-C₈) alkoxy- (C₁-C₈) alkyl, (C₇-C₁₂) aralkoxy- (C₁-C₈) alkyl, (C₆-C₁₂) aryloxy- (C₁-C₈) alkyl, (C₁-C₁₀) alkanoyl, optionally substituted (C₇-C₁₆) aralkanoyl, optionally substituted (C₆-C₁₂) aryl.

Vorzugsweise bilden die Reste R¹ und R² oder R² und R³ und das sie tragende Pyridin bzw. Pyridazin einen 5,6,7,8-Tetrahydroisochinolin-, einen 5,6,7,8- Tetrahydrochinolin- oder einen 5,6,7,8-Tetrahydrocinnolin-Ring, oder
einen carbocylischen oder einen heterocyclischen, gegebenenfalls mit Fluor, Chlor, (C₁-C₈)-Alkoxy oder einem Carbamoyl-Rest substituierten 5- oder 6- gliedrigen aromatischen Ring.The radicals R 1 and R 2 or R 2 and R 3 and the pyridine or pyridazine carrying them preferably form a 5,6,7,8-tetrahydroisoquinoline, a 5,6,7,8-tetrahydroquinoline or a 5,6,7, 8-tetrahydrocinnoline ring, or
a carbocyclic or a heterocyclic, optionally substituted with fluorine, chlorine, (C₁-C₈) alkoxy or a carbamoyl radical 5- or 6-membered aromatic ring.

R¹ und R² oder R² und R³ bilden zusammen mit dem sie tragenden Pyridin bzw. Pyridazin folgende heterocyclische Ringsysteme:R¹ and R² or R² and R³ together with the pyridine or Pyridazine the following heterocyclic ring systems:

Thienopyridine,
Furanopyridine,
Pyridopyridine,
Pyrimidinopyridine,
Imidazopyridine,
Thiazolopyridine,
Oxazolopyridine,
Chinolin, Isochinolin und
Cinnolin.Thienopyridines,
Furanopyridines,
Pyridopyridines,
Pyrimidinopyridines,
Imidazopyridines,
Thiazolopyridines,
Oxazolopyridines,
Quinoline, isoquinoline and
Cinnolin.

R⁴ bedeutet einen verzweigten oder unverzweigten (C₁-C₂₀)-Alkylrest oder einen Arylrest oder einen Heteroarylrest,
wobei diese Reste substituiert sind mit einem oder mehreren Resten aus der Reihe
(C₂-C₁₂)-Alkenyl, (C₂-C₁₂)-Alkinyl, (C₆-C₁₂)-Aryl, Heteroaryl, (C₆-C₁₂)-Aralkyloxy, Heteroalkyloxy, Wasserstoff, Hydroxy, Halogen, Cyano, Trifluormethyl, Nitro, Carboxy, (C₁-C₁₂)-Alkyl, (C₃-C₈)-Cycloalkyl, (C₆-C₁₂)-Aryl, (C₇-C₁₆)-Aralkyl, (C₂-C₁₂)-Alkenyl, (C₂-C₁₂)-Alkinyl, (C₁-C₁₂)-Alkoxy, (C₃-C₈)- Cycloalkoxy, (C₁-C₁₂)-Alkoxy-(C₁-C₁₂)alkyl, (C₁-C₁₂)-Alkoxy-(C₁-C₁₂)alkoxy, (C₆-C₁₂)-Aryloxy, (C₇-C₁₆)-Aralkyloxy, (C₆-C₁₂)-Aryloxy-(C₁-C₆)-alkoxy, (C₇- C₁₆)-Aralkoxy-(C₁-C₆)-alkoxy, -O-[CH2-]xCfH(2f+1-g)Fg, -OCF₂Cl, -OCF₂-CHFCl,
(C₁-C₁₂)-Alkylcarbonyl, (C₃-C₈)-Cycloalkylcarbonyl, (C₆-C₁₂)-Arylcarbonyl, (C₇-C₁₆)-Aralkylcarbonyl, Cinnamoy, (C₂-C₁₂)-Alkenylcarbonyl, (C₂-C₁₂)-Alkinylcarbonyl,
(C₁-C₁₂)-Alkoxycarbonyl, (C₁-C₁₂)-Alkoxy-(C₁-C₁₂)-alkoxycarbonyl, (C₆-C₁₂)- Aryloxycarbonyl, (C₇-C₁₆)-Aralkoxycarbonyl, (C₃-C₈)-Cycloalkoxycarbonyl, (C₂- C₁₂)-Alkenyloxycarbonyl, (C₂-C₁₂)-Alkinyloxycarbonyl,
(C₁-C₁₂)-Alkylcarbonyloxy, (C₃-C₈)-Cycloalkylcarbonyloxy,
(C₆-C₁₂)-Arylcarbonyloxy, (C₇-C₁₆)-Aralkylcarbonyloxy, Cinnamoyloxy, (C₂- C₁₂)-Alkenylcarbonyloxy, (C₂-C₁₂)-Alkinylcarbonyloxy,
(C₁-C₁₂)-Alkoxycarbonyloxy, (C₁-C₁₂)-Alkoxy-(C₁-C₁₂)-alkoxycarbonyloxy, (C₆-C₁₂)-Aryloxycarbonyloxy, (C₇-C₁₆)-Aralkyloxycarbonyloxy, (C₂-C₈)- Cycloalkoxycarbonyloxy, (C₂-C₁₂)-Alkenyloxycarbonyloxy, (C₂-C₁₂)- Alkinyloxycarbonyloxy,
Carbamoyl, N-(C₁-C₁₂)-Alkylcarbamoyl, N,N-Di-(C₁-C₁₂)-alkylcarbamoyl, N- (C₃-C₈)-Cycloalkylcarbamoyl, N,N-Dicyclo(C₃-C₈)-alkylcarbamoyl, N-(C₁-C₁₀)- Alkyl-N-(C₃-C₈)-Cycloalkylcarbamoyl, N-(C₃-C₈)-Cycloalkyl-(C₁-C₆)- alkyl)carbamoyl, N-(C₁-C₆)-Alkyl-N-((C₃-C₈-Cycloalkyl-(C₁-C₆)-alkyl)carbamoyl, N-(+)-Dehydroabietylcarbamoyl, N-(C₁-C₆)-Alkyl-N-Dehydroabietylcarbamoyl, N- (C₆-C₁₂)-Arylcarbamoyl, N-(C₇-C₁₆)-Aralkylcarbamoyl, N-(C₁-C₁₀)-Alkyl-N-(C₆- C₁₆)arylcarbamoyl, N-(C₁-C₁₀)-Alkyl-N-(C₇-C₁₆)-Aralkylcarbamoyl, N-((C₁-C₁₀)- Alkoxy-(C₁-C₁₀)alkyl)carbamoyl, N-((C₆-C₁₆)-Aryloxy-(C₁-C₁₀)alkyl)carbamoyl, N-((C₇-C₁₆)-Aralkyloxy-(C₁-C₁₀)alkyl)carbamoyl, N-(C₁-C₁₀)-Alkyl-N-((C₁-C₁₀)- Alkoxy-(C₁-C₁₀)alkyl)carbamoyl,
N-(C₁-C₁₀)-Alkyl-N-((C₆-C₁₂)-Aryloxy-(C₁-C₁₀)alkyl)carbamoyl, N-(C₁-C₁₀)-Alkyl-N-((C₇-C₁₆)Aralkyloxy-(C₁-C₁₀)alkyl)carbamoyl, CON(CH₂)h, worin eine CH₂-Gruppe durch O, S, N-(C₁-C₈)Alkylimino, N-(C₃-C₈)- Cycloalkylimino, N-(C₃-C₈)-Cycloalkyl-(C₁-C₄)alkylimino, N-(C₆-C₁₂)-Arylimino, N-(C₇-C₁₆)-Aralkylimino oder N-(C₁-C₄)-Alkoxy (C₁-C₆) alkylimino ersetzt ein kann und h 3 bis 7 bedeutet,
Carbamoyloxy, N-(C₁-C₁₂)-Alkylcarbamoyloxy, N,N-Di-(C₁-C₁₂)- alkylcarbamoyloxy, N-(C₃-C₈)-Cycloalkylcarbamoyloxy, N-(C₆-C₁₂)- Arylcarbamoyloxy, N-(C₇-C₁₆)-Aralkylcarbamoyloxy, N-(C₁-C₁₀)-Alkyl-N-(C₆- C₁₂)arylcarbamoyloxy, N-(C₁-C₁₀)-Alkyl-N-(C₇-C₁₆)-Aralkylcarbamoyloxy, N-((C₁-C₁₀)alkyl))carbamoyloxy, N-((C₆-C₁₂)-Aryloxy-(C₁- C₁₀)alkyl)carbamoyloxy, N-((C₇-C₁₆)-Aralkyloxy-(C₁-C₁₀)alkyl)carbamoyloxy, N-(C₁-C₁₀)-Alkyl-N-((C₁-C₁₀)-Alkoxy-(C₁-C₁₀)alkyl)carbamoyloxy, N-(C₁-C₁₀)-Alkyl-N-((C₆-C₁₆)-Aryloxy-(C₁-C₁₀)alkyl)carbamoyloxy, N-(C₁-C₁₀)-Alkyl-N-((C₇-C₁₆)-Aralkyloxy-(C₁-C₁₀)alkyl)carbamoyloxy,
Amino, (C₁-C₁₂)-Alkylamino, Di-(C₁-C₁₂)alkylamino, (C₃-C₈)-Cycloalkylamino, (C₃-C₁₂)-Alkenylamino, (C₃-C₁₂) Alkinylamino, N-(C₆-C₁₂)-Arylamino, N-(C₇- C₁₁)-Aralkylamino, N-Alkyl-Aralkylamino, N-Alkyl-Arylamino, (C₁-C₁₂)- Alkoxyamino, (C₁-C₁₂)-Alkoxy-N-(C₁-C₁₀)-alkylamino,
(C₁-C₁₂)-Alkanoylamino, (C₃-C₈)-Cycloalkanoylamino, (C₆-C₁₂)-Aroylamino, (C₇-C₁₆)-Aralkanoylamino, (C₁-C₁₂)-Alkanoyl-N-(C₁-C₁₀)-alkylamino, (C₃-C₈)- Cycloalkanoyl-N-(C₁-C₁₀)-alkylamino, (C₆-C₁₂)-Aroyl-N-(C₁-C₁₀)alkylamino, (C₇- C₁₁)-Aralkanoyl-N-(C₁-C₁₀)-alkylamino,
(C₁-C₁₂)-Alkanoylamino-(C₁-C₈)-alkyl, (C₃-C₈)-Cycloalkanoylamino-(C₁-C₈)alkyl, (C₆-C₁₆)-Aroylamino-(C₁-C₈)-alkyl, (C₇-C₁₆)-Aralkanoylamino-(C₁ -C₈)-alkyl, Amino-(C₁-C₁₀)-alkyl, N-(C₁-C₁₀)alkylamino-(C₁-C₁₀)alkyl, N,N-Di-(C₁- C₁₀)alkylamino-(C₁-C₁₀)alkyl, (C₃-C₈)cycloalkylamino-(C₁-C₁₀)alkyl,
(C₁-C₁₂)-Alkylmercapto, (C₁-C₁₂)-Alkylsulfinyl, (C₁-C₁₂)-Alkylsulfonyl, (C₆-C₁₂)- Arylmercapto, (C₆-C₁₆)-Arylsulfinyl, (C₆-C₁₆)-Arylsulfonyl, (C₇-C₁₆)- Aralkylmercapto, (C₇-C₁₆)-Aralkylsulfinyl, (C₇-C₁₆)-Aralkylsulfonyl,
Sulfamoyl, N-(C₁-C₁₀)-Alkylsulfamoyl, N,N-Di-(C₁-C₁₀)-alkylsulfamoyl, (C₃-C₈)- Cycloalkylsulfamoyl, N-(C₆-(C₁₂)-Arylsulfamoyl, N-(C₇-C₁₆)-Aralkylsulfamoyl, N-(C₁-C₁₀)-Alkyl-N-(C₆-C₁₂)-Arylsulfamoyl, N-(C₁-C₁₀)-Alkyl-N-(C₇-C₁₆)- Aralkylsulfamoyl, (C₁-C₁₀)-Alkyl-sulfonamido, N-((C₁-C₁₀)alkyl)-(C₁- C₁₀)alkylsulfonamido, (C₇-C₁₆)-Aralkylsulfonamido, N-((C₁-C₁₀)alkyl-(C₇-C₁₆)- Aralkylsulfonamido,
wobei die Reste, die einen Arylrest enthalten ihrerseits am Aryl substituiert sein können durch 1 bis 5 gleiche oder verschiedene Reste aus der Reihe: Hydroxy, Halogen, Cyano, Trifluormethyl, Nitro, Carboxy, (C₁-C₁₂) Alkyl, (C₃-C₈)-Cycloalkyl, (C₆-C₁₂)-Aryl, (C₇-C₁₆)-Aralkyl, (C₁-C₁₂)-Alkoxy, (C₁-C₁₂)- Alkoxy-(C₁-C₁₂)alkyl, (C₁-C₁₂)-Alkoxy-(C₁-C₁₂)alkoxy, (C₆-C₁₂)-Aryloxy, (C₇-C₁₆)-Aralkyloxy, (C₁-C₈) Hydroxyalkoxy, (C₁-C₁₂)-Alkylcarbonyl, (C₃-C₈)-Cycloalkylcarbonyl, (C₆-C₁₂)-Arylcarbonyl, (C₇- C₁₆)-Aralkylcarbonyl.R⁴ represents a branched or unbranched (C₁-C₂₀) alkyl radical or an aryl radical or a heteroaryl radical,
these radicals being substituted by one or more radicals from the series
(C₂-C₁₂) alkenyl, (C₂-C₁₂) alkynyl, (C₆-C₁₂) aryl, heteroaryl, (C₆-C₁₂) aralkyloxy, heteroalkyloxy, hydrogen, hydroxy, halogen, cyano, trifluoromethyl, nitro, carboxy, (C₁-C₁₂) alkyl, (C₃-C₈) cycloalkyl, (C₆-C₁₂) aryl, (C₇-C₁₆) aralkyl, (C₂-C₁₂) alkenyl, (C₂-C₁₂) alkynyl, (C₁ -C₁₂) alkoxy, (C₃-C₈) - cycloalkoxy, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxy, (C₆-C₁₂) - Aryloxy, (C₇-C₁₆) aralkyloxy, (C₆-C₁₂) aryloxy- (C₁-C₆) alkoxy, (C₇- C₁₆) aralkoxy- (C₁-C₆) alkoxy, -O- [CH 2- ] x C f H (2f + 1-g) F g , -OCF₂Cl, -OCF₂-CHFCl,
(C₁-C₁₂) alkylcarbonyl, (C₃-C₈) cycloalkylcarbonyl, (C₆-C₁₂) arylcarbonyl, (C₇-C₁₆) aralkylcarbonyl, cinnamoy, (C₂-C₁₂) alkenylcarbonyl, (C₂-C₁₂) alkynylcarbonyl,
(C₁-C₁₂) alkoxycarbonyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyl, (C₆-C₁₂) aryloxycarbonyl, (C₇-C₁₆) aralkoxycarbonyl, (C₃-C₈) cycloalkoxycarbonyl, (C₂ - C₁₂) alkenyloxycarbonyl, (C₂-C₁₂) alkynyloxycarbonyl,
(C₁-C₁₂) alkylcarbonyloxy, (C₃-C₈) cycloalkylcarbonyloxy,
(C₆-C₁₂) arylcarbonyloxy, (C₇-C₁₆) aralkylcarbonyloxy, cinnamoyloxy, (C₂- C₁₂) alkenylcarbonyloxy, (C₂-C₁₂) alkynylcarbonyloxy,
(C₁-C₁₂) alkoxycarbonyloxy, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyloxy, (C₆-C₁₂) aryloxycarbonyloxy, (C₇-C₁₆) aralkyloxycarbonyloxy, (C₂-C₈) - cycloalkoxycarbonyloxy, (C₂ -C₁₂) alkenyloxycarbonyloxy, (C₂-C₁₂) alkynyloxycarbonyloxy,
Carbamoyl, N- (C₁-C₁₂) alkylcarbamoyl, N, N-di- (C₁-C₁₂) alkylcarbamoyl, N- (C₃-C₈) cycloalkylcarbamoyl, N, N-dicyclo (C₃-C₈) alkylcarbamoyl, N - (C₁-C₁₀) - alkyl-N- (C₃-C₈) -cycloalkylcarbamoyl, N- (C₃-C₈) -cycloalkyl- (C₁-C₆) - alkyl) carbamoyl, N- (C₁-C₆) -alkyl-N - ((C₃-C₈-Cycloalkyl- (C₁-C₆) -alkyl) carbamoyl, N - (+) - dehydroabietylcarbamoyl, N- (C₁-C₆) alkyl-N-dehydroabietylcarbamoyl, N- (C₆-C₁₂) arylcarbamoyl , N- (C₇-C₁₆) aralkylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₆- C₁₆) arylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₇-C₁₆) aralkylcarbamoyl, N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N - ((C₆-C₁₆) aryloxy- (C₁-C₁₀) alkyl) carbamoyl, N - ((C₇-C₁₆) aralkyloxy - (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl,
N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyl, CON (CH₂) h , wherein a CH₂ group by O, S, N- (C₁-C₈) alkylimino, N- (C₃-C₈) - cycloalkylimino, N- (C₃-C₈ ) -Cycloalkyl- (C₁-C₄) alkylimino, N- (C₆-C₁₂) arylimino, N- (C₇-C₁₆) aralkylimino or N- (C₁-C₄) alkoxy (C₁-C₆) alkylimino can be replaced and h means 3 to 7,
Carbamoyloxy, N- (C₁-C₁₂) alkylcarbamoyloxy, N, N-Di- (C₁-C₁₂) alkylcarbamoyloxy, N- (C₃-C₈) cycloalkylcarbamoyloxy, N- (C₆-C₁₂) arylcarbamoyloxy, N- (C₇ -C₁₆) aralkylcarbamoyloxy, N- (C₁-C₁₀) alkyl-N- (C₆- C₁₂) arylcarbamoyloxy, N- (C₁-C₁₀) alkyl-N- (C₇-C₁₆) aralkylcarbamoyloxy, N - ((C₁ -C₁₀) alkyl)) carbamoyloxy, N - ((C₆-C₁₂) aryloxy- (C₁- C₁₀) alkyl) carbamoyloxy, N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₆) aryloxy- ( C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyloxy,
Amino, (C₁-C₁₂) alkylamino, di- (C₁-C₁₂) alkylamino, (C₃-C₈) -cycloalkylamino, (C₃-C₁₂) alkenylamino, (C₃-C₁₂) alkynylamino, N- (C₆-C₁₂) - Arylamino, N- (C₇- C₁₁) aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C₁-C₁₂) alkoxyamino, (C₁-C₁₂) alkoxy-N- (C₁-C₁₀) alkylamino,
(C₁-C₁₂) alkanoylamino, (C₃-C₈) cycloalkanoylamino, (C₆-C₁₂) aroylamino, (C₇-C₁₆) aralkanoylamino, (C₁-C₁₂) alkanoyl-N- (C₁-C₁₀) alkylamino, (C₃-C₈) - cycloalkanoyl-N- (C₁-C₁₀) alkylamino, (C₆-C₁₂) aroyl-N- (C₁-C₁₀) alkylamino, (C₇- C₁₁) aralkanoyl-N- (C₁-C₁₀) -alkylamino,
(C₁-C₁₂) alkanoylamino- (C₁-C₈) alkyl, (C₃-C₈) cycloalkanoylamino- (C₁-C₈) alkyl, (C₆-C₁₆) aroylamino- (C₁-C₈) alkyl, (C₇- C₁₆) aralkanoylamino- (C₁ -C₈) alkyl, amino- (C₁-C₁₀) alkyl, N- (C₁-C₁₀) alkylamino- (C₁-C₁₀) alkyl, N, N-di- (C₁- C₁₀) alkylamino- (C₁-C₁₀) alkyl, (C₃-C₈) cycloalkylamino- (C₁-C₁₀) alkyl,
(C₁-C₁₂) alkylmercapto, (C₁-C₁₂) alkylsulfinyl, (C₁-C₁₂) alkylsulfonyl, (C₆-C₁₂) arylmercapto, (C₆-C₁₆) arylsulfinyl, (C₆-C₁₆) arylsulfonyl, (C₆ -C₁₆) aralkylmercapto, (C₇-C₁₆) aralkylsulfinyl, (C₇-C₁₆) aralkylsulfonyl,
Sulfamoyl, N- (C₁-C₁₀) alkylsulfamoyl, N, N-di- (C₁-C₁₀) alkylsulfamoyl, (C₃-C₈) cycloalkylsulfamoyl, N- (C₆- (C₁₂) arylsulfamoyl, N- (C₇- C₁₆) aralkylsulfamoyl, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₂) arylsulfamoyl, N- (C₁-C₁₀) alkyl-N- (C₇-C₁₆) aralkylsulfamoyl, (C₁-C₁₀) Alkyl sulfonamido, N - ((C₁-C₁₀) alkyl) - (C₁- C₁₀) alkylsulfonamido, (C₇-C₁₆) aralkylsulfonamido, N - ((C₁-C₁₀) alkyl- (C₇-C₁₆) aralkylsulfonamido,
the radicals which contain an aryl radical in turn can be substituted on the aryl by 1 to 5 identical or different radicals from the series: hydroxy, halogen, cyano, trifluoromethyl, nitro, carboxy, (C₁-C₁₂) alkyl, (C₃-C₈) -Cycloalkyl, (C₆-C₁₂) aryl, (C₇-C₁₆) aralkyl, (C₁-C₁₂) alkoxy, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxy, (C₆-C₁₂) aryloxy, (C₇-C₁₆) aralkyloxy, (C₁-C₈) hydroxyalkoxy, (C₁-C₁₂) alkylcarbonyl, (C₃-C₈) cycloalkylcarbonyl, (C₆-C₁₂ ) Arylcarbonyl, (C₇- C₁₆) aralkylcarbonyl.

Steht Q in der Bedeutung von NR′, so steht R⁴ in der Bedeutung von R′′, wobei R′ und R′′ gleich oder verschieden sind und Wasserstoff, (C₆-C₁₂)-Aryl, (C₁-C₈)- Alkyl, (C₁-C₈)-Alkoxy-(C₁-C₈)alkyl, (C₇-C₁₂)-Aralkoxy-(C₁-C₈)alkyl, (C₆-C₁₂)- Aryloxy-(C₁-C₈)-alkyl, (C₁-C₁₀)-Alkanoyl, ggf. substituiertes (C₇-C₁₆)-Aralkanoyl, ggf. substituiertes (C₆-C₁₂)-Aroyl bedeuten, oder
R′ und R′′ gemeinsam für -[CH₂]h stehen, worin eine CH₂-Gruppe durch O, S, N-Acylimino oder N-(C₁-C₁₀)-Alkoxycarbonylimino ersetzt sein kann, undIf Q is NR ′, R⁴ is R ′ ′, where R ′ and R ′ ′ are the same or different and are hydrogen, (C₆-C₁₂) aryl, (C₁-C₈) alkyl, (C₁-C₈) alkoxy- (C₁-C₈) alkyl, (C₇-C₁₂) aralkoxy- (C₁-C₈) alkyl, (C₆-C₁₂) aryloxy- (C₁-C₈) alkyl, (C₁-C₁₀ ) -Alkanoyl, optionally substituted (C₇-C₁₆) aralkanoyl, optionally substituted (C₆-C₁₂) aryl, or
R ′ and R ′ ′ together represent - [CH₂] h , in which a CH₂ group can be replaced by O, S, N-acylimino or N- (C₁-C₁₀) alkoxycarbonylimino, and

f = 1 bis 8,
g = 0, 1 bis (2f+1),
x = 0 bis 3,
h = 3 bis 6 bedeutenf = 1 to 8,
g = 0.1 to (2f + 1),
x = 0 to 3,
h = 3 to 6 mean

einschließlich der physiologisch wirksamen Salze, wobei 3-Benzyloxypyridin-2-carbonsäure-L-threonylamid und 3-Benzyloxypyridin- 2-carbonsäure-((Fmoc-Phg)L-threonyl)amid-Hydrochlorid ausgenommen sind.including the physiologically active salts, where 3-benzyloxypyridine-2-carboxylic acid-L-threonylamide and 3-benzyloxypyridine- 2-carboxylic acid - ((Fmoc-Phg) L-threonyl) amide hydrochloride are excluded.

Unter Aryl wird insbesondere Phenyl und Naphthyl, unter Heteroaryl insbesondere Pyridin und unter Cycloalkyl vorzugsweise Cyclohexyl verstanden.Aryl is especially phenyl and naphthyl, heteroaryl in particular pyridine and cycloalkyl is preferably understood to mean cyclohexyl.

Die Erfindung umfaßt weiterhin Salze der Verbindungen der allgemeinen Formel I.The invention further encompasses salts of the compounds of the general Formula I.

Die Salzbildung mit basischen Reagenzien erfolgt an der Carboxylat-Funktion.Salt formation with basic reagents takes place at the carboxylate function.

Zur Anwendung kommende Reagenzien sind beispielsweise Alkoholate, Hydroxide, Carbonate, Hydrogencarbonate, Hydrogenphosphate, Metallorganyle der Alkali- und Erdalkalielemente, der Elemente der 3. und 4. Hauptgruppe des Periodensystems und der Elemente der Übergangsmetalle,
Amine, ggf. 1- bis 3fach substituiert mit (C₁-C₈)-Hydroxyalkyl, (C₁-C₄)-Alkoxy- (C₁-C₈)-alkyl, Phenyl, Benzyl oder (C₁-C₈)-Alkyl, welches 1- bis 3fach substituiert sein kann mit Hydroxy oder (C₁-C₄)-Alkoxy, beispielsweise Tromethan, (Tris-Puffer), 2-Aminoethanol, 3-Aminopropanol, Hydroxylamin, Dimethylhydroxylamin, 2-Methoxyethylamin, 3-Ethoxypropylamin, und basische Aminosäuren und -derivate, wie Aminosäureester, Histidin, Arginin und Lysin und deren Derivate, sowie Arzneimittel, die eine basische Gruppe enthalten, wie beispielsweise ®Amilorid, ®Verapamil und Betablocker.Reagents used are, for example, alcoholates, hydroxides, carbonates, hydrogen carbonates, hydrogen phosphates, metal organyls of the alkali and alkaline earth elements, the elements of the 3rd and 4th main group of the periodic table and the elements of the transition metals,
Amines, optionally 1 to 3 times substituted with (C₁-C₈) hydroxyalkyl, (C₁-C₄) alkoxy- (C₁-C₈) alkyl, phenyl, benzyl or (C₁-C₈) alkyl, which 1- to Can be substituted 3 times with hydroxy or (C₁-C₄) alkoxy, for example tromethane, (Tris buffer), 2-aminoethanol, 3-aminopropanol, hydroxylamine, dimethylhydroxylamine, 2-methoxyethylamine, 3-ethoxypropylamine, and basic amino acids and derivatives , such as amino acid esters, histidine, arginine and lysine and their derivatives, and also medicaments which contain a basic group, such as, for example, ®Amilorid, ®Verapamil and beta blockers.

Die Erfindung betrifft weiterhin die Verbindungen, gemäß Formel I, zuzüglich 3-Benzyloxypyridin 2-carbonsäure-L-threonylamid und 3-Benzyloxypyridin-2- carbonsäure-((Fmoc-Phg)L-threonyl)amid-Hydrochlorid zur Anwendung der Arzneimittel.The invention further relates to the compounds according to formula I, plus 3-benzyloxypyridine, 2-carboxylic acid-L-threonylamide and 3-benzyloxypyridine-2- carboxylic acid - ((Fmoc-Phg) L-threonyl) amide hydrochloride for the application of Drug.

Bevorzugt sind Verbindungen der Formel I, in derPreferred compounds of the formula I are those in which

Q = O,
X = O,
Y = CR³ oder, falls R¹ und R² einen Cyclus bilden, Y = N,
m = 0,Q = O,
X = O,
Y = CR³ or, if R¹ and R² form a cycle, Y = N,
m = 0,

A (C₁-C₃)-Alkylen, das gegebenenfalls einfach substituiert ist mit Halogen, Cyano, Trifluormethyl, (C₁-C₆)-Alkyl, (C₁-C₆)-Hydroxyalkyl, (C₁-C₆)- Alkoxy, -O-[CH₂]x-CfH(2f+1-g)Fg oder
A -CHR⁵- bedeutet, wobei R⁵ einen der Substituenten des α-C-Atoms einer α-Aminosäure bedeutet, insbesondere einer natürlichen L-Aminosäure und ihres D-Isomeren,
B CO₂H
R² Wasserstoff, (C₁-C₁₀)-Alkyl, (C₁-C₁₀)-Alkoxy, Halogen, CN, Trifluormethyl, (C₁-C₈)-Hydroxyalkyl, (C₁-C₁₀)-Alkoxycarbonyl, (C₃-C₁₀)- Cycloalkoxycarbonyl, (C₁-C₁₀)-Alkanoyl, (C₇-C₁₂)-Aralkanoyl, (C₆-C₁₂)- Aroyl, -O-[CH₂]x-CfH(2f+1-g)Fg, NR′R′′, (C₁-C₁₀)-Alkylmercapto, (C₁-C₁₀)- Alkylsulfinyl, (C₁-C₁₀)-Alkylsulfonyl, (C₆-C₁₂)-Arylmercapto, (C₆-C₁₂)- Arylsulfinyl), (C₆-C₁₂)-Arylsulfonyl, (C₇-C₁₂)-Aralkylmercapto, (C₇-C₁₂)- Aralkylsulfinyl, (C₇-C₁₂)-Aralkylsulfonyl, (C₆-C₁₂)-Aryloxy, (C₇-C₁₆)- Aralkyloxy, Carboxy,
Carbamoyl, N-(C₁-C₁₀)-Alkylcarbamoyl, N,N-Di-(C₁-C₁₀)-alkylcarbamoyl, N-(C₃-C₈)-Cycloalkyl, N-(C₃-C₈)-Cycloalkylcarbamoyl, (C₁-C₄)- alkylcarbamoxyl, N-(C₆-C₁₂)-Arylcarbamoyl, N-(C₇-C₁₆)-Aralkylcarbamoyl, N-(C₁-C₆)-Alkyl-N-(C₆-C₁₂)arylcarbamoyl, N-(C₁-C₆)-Alkyl-N-(C₇-C₁₆)- Aralkylcarbamoyl, N-((C₁-C₆)-Alkoxy- (C₁-C₆)alkyl)carbamoyl,
wobei Aryl in der Weise substituiert ist wie für R¹ und R³ definiert,
R¹ und R³ gleich oder verschieden sind und Wasserstoff, Halogen, (C₁-C₁₂)- Alkyl, (C₁-C₁₂)-Alkoxy, -O-[CH₂]x-CfH(2f+1-g)Halg, (C₁-C₁₂)-Alkoxy- (C₁-C₁₂)-alkyl, (C₁-C₈)-Alkoxy-(C₁-C₁₂)-alkoxy, (C₁-C₁₂)-Alkoxy-(C₁-C₈)- alkoxy-(C₂-C₆)-alkyl, (C₇-C₁₁)-Aralkyloxy, (C₃-C₈)-Cycloalkyl, (C₃-C₈)- Cycloalkyl-(C₁-C₈)-alkyl, (C₃-C₈)-Cycloalkyloxy, (C₃-C₈)-Cycloalkyl-(C₁- C₈)-alkoxy, (C₃-C₈)-Cycloalkyloxy-(C₁-C₈)-alkyl, (C₃-C₈)-Cycloalkyloxy- (C₁-C₈)-alkoxy, (C₃-C₈)-Cycloalkyl-(C₁-C₆)-alkyl-(C₁-C₆)-alkoxy, (C₃-C₈)- Cycloalkyl-(C₁-C₆)-alkoxy-(C₁-C₆)-alkyl, (C₃-C₈)-Cycloalkoxy-(C₁-C₆)- alkoxy (C₁-C₆)alkyl, NR′ R′′, (C₁-C₈)-Alkylmercapto, (C₁-C₈)-Alkylsulfinyl oder (C₁-C₈)-Alkylsulfonyl, (C₆-C₁₂)-Arylmercapto, (C₆-C₁₂)-Arylsulfinyl, (C₆-C₁₂)-Arylsulfonyl, (C₇-C₁₂)-Aralkylmercapto, (C₇-C₁₁)-Aralkylsulfinyl, (C₇-C₁₁)-Aralkylsulfonyl, substituiertes (C₆-C₁₂)-Aryloxy-(C₁-C₆)-alkyl, (C₇-C₁₁)-Aralkoxy-(C₁-C₆)-alkyl, (C₆-C₁₂)-Aryloxy-(C₁-C₆)-alkoxy-(C₁-C₆)- alkyl, (C₇-C₁₁)-Aralkyloxy-(C₁-C₆)-alkoxy-(C₁-C₆)alkyl, (C₆-C₁₂)-Aryloxy, (C₇-C₁₁)-Aralkyloxy, (C₆-C₁₂)-Aryloxy-(C₁-C₆)-alkoxy oder (C₇-C₁₁)- Aralkoxy-(C₁-C₆)-alkoxy bedeutet, wobei ein aromatischer Rest mit 1,2, 3, 4 oder 5 gleichen oder verschiedenen Substituenten aus der Reihe Wasserstoff, Halogen, Cyano, Nitro, Trifluormethyl, (C₁-C₆)-Alkyl, (C₁- C₆)-Hydroxyalkyl, (C₁-C₆)-Alkoxy, -O-[CH₂]xCfH(2f+1-g)Fg, -OCF₂Cl, -O-CF₂-CHFCl, (C₁-C₆)-Alkylmercapto, (C₁-C₆)-Alkylsulfinyl, (C₁ -C₆)- Alkylsulfonyl, (C₁-C₆)-Alkylcarbonyl, (C₁-C₆)-Alkoxycarbonyl, Carbamoyl, N-(C₁-C₄)-Alkylcarbamoyl, N,N-Di-(C₁-C₄)-alkylcarbamoyl, (C₁-C₆)- Alkylcarbonyloxy, (C₃-C₈)-Cycloalkylcarbamoyl, Phenyl, Benzyl, Phenoxy, Benzyloxy, NR′R′′, Phenylmercapto, Phenylsulfonyl, Phenylsulfinyl, Sulfamoyl, N-(C₁-C₄)-Alkylsulfamoyl oder N,N-Di-(C₁-C₄)-alkylsulfamoyl trägt, oder gegebenenfalls bis zu 3 der vorstehend genannten gleichen oder verschiedenen Substituenten trägt und zwei benachbarte C-Atome des Aralkyloxyrestes gemeinsam eine Kette -[CH₂-] und/oder -CH=CH- CH=CH- tragen, wobei eine CH₂-Gruppe der Kette gegebenenfalls durch O, S, SO, SO₂ oder NR′ ersetzt ist.A (C₁-C₃) alkylene, which is optionally monosubstituted with halogen, cyano, trifluoromethyl, (C₁-C₆) alkyl, (C₁-C₆) hydroxyalkyl, (C₁-C₆) alkoxy, -O- [CH₂ ] x -C f H (2f + 1-g) F g or
A means -CHR⁵-, where R⁵ means one of the substituents of the α-C atom of an α-amino acid, in particular a natural L-amino acid and its D isomer,
B CO₂H
R² is hydrogen, (C₁-C₁₀) alkyl, (C₁-C₁₀) alkoxy, halogen, CN, trifluoromethyl, (C₁-C₈) hydroxyalkyl, (C₁-C₁₀) alkoxycarbonyl, (C₃-C₁₀) cycloalkoxycarbonyl, ( C₁-C₁₀) alkanoyl, (C₇-C₁₂) aralkanoyl, (C₆-C₁₂) aroyl, -O- [CH₂] x -C f H (2f + 1-g) F g , NR′R ′ ′, (C₁-C₁₀) alkylmercapto, (C₁-C₁₀) alkylsulfinyl, (C₁-C₁₀) alkylsulfonyl, (C₆-C₁₂) arylmercapto, (C₆-C₁₂) arylsulfinyl), (C₆-C₁₂) arylsulfonyl, ( C₇-C₁₂) aralkylmercapto, (C₇-C₁₂) aralkylsulfinyl, (C₇-C₁₂) aralkylsulfonyl, (C₆-C₁₂) aryloxy, (C₇-C₁₆) aralkyloxy, carboxy,
Carbamoyl, N- (C₁-C₁₀) alkylcarbamoyl, N, N-di- (C₁-C₁₀) alkylcarbamoyl, N- (C₃-C₈) cycloalkyl, N- (C₃-C₈) cycloalkylcarbamoyl, (C₁-C₄ ) - alkylcarbamoxyl, N- (C₆-C₁₂) arylcarbamoyl, N- (C₇-C₁₆) aralkylcarbamoyl, N- (C₁-C₆) alkyl-N- (C₆-C₁₂) arylcarbamoyl, N- (C₁-C₆) -Alkyl-N- (C₇-C₁₆) aralkylcarbamoyl, N - ((C₁-C₆) alkoxy- (C₁-C₆) alkyl) carbamoyl,
where aryl is substituted in the manner defined for R¹ and R³,
R¹ and R³ are the same or different and are hydrogen, halogen, (C₁-C₁₂) alkyl, (C₁-C₁₂) alkoxy, -O- [CH₂] x -C f H (2f + 1-g) Hal g , ( C₁-C₁₂) alkoxy- (C₁-C₁₂) alkyl, (C₁-C₈) alkoxy- (C₁-C₁₂) alkoxy, (C₁-C₁₂) alkoxy- (C₁-C₈) - alkoxy- (C₂- C₆) alkyl, (C₇-C₁₁) aralkyloxy, (C₃-C₈) cycloalkyl, (C₃-C₈) - cycloalkyl- (C₁-C₈) alkyl, (C₃-C₈) cycloalkyloxy, (C₃-C₈) -Cycloalkyl- (C₁- C₈) alkoxy, (C₃-C₈) -cycloalkyloxy- (C₁-C₈) alkyl, (C₃-C₈) -cycloalkyloxy- (C₁-C₈) alkoxy, (C₃-C₈) cycloalkyl - (C₁-C₆) alkyl- (C₁-C₆) alkoxy, (C₃-C₈) - cycloalkyl- (C₁-C₆) alkoxy- (C₁-C₆) alkyl, (C₃-C₈) cycloalkoxy- ( C₁-C₆) - alkoxy (C₁-C₆) alkyl, NR ′ R ′ ′, (C₁-C₈) alkylmercapto, (C₁-C₈) alkylsulfinyl or (C₁-C₈) alkylsulfonyl, (C₆-C₁₂) arylmercapto , (C₆-C₁₂) arylsulfinyl, (C₆-C₁₂) arylsulfonyl, (C₇-C₁₂) aralkylmercapto, (C₇-C₁₁) aralkylsulfinyl, (C₇-C ₁) aralkylsulfonyl, substituted (C₆-C₁₂) aryloxy- (C₁-C₆) alkyl, (C₇-C₁₁) aralkoxy- (C₁-C₆) alkyl, (C₆-C₁₂) aryloxy- (C₁-C₆ ) -alkoxy- (C₁-C₆) alkyl, (C₇-C₁₁) aralkyloxy- (C₁-C₆) alkoxy- (C₁-C₆) alkyl, (C₆-C₁₂) aryloxy, (C₇-C₁₁) aralkyloxy , (C₆-C₁₂) aryloxy- (C₁-C₆) -alkoxy or (C₇-C₁₁) - aralkoxy- (C₁-C-) -alkoxy means, where an aromatic radical with 1,2, 3, 4 or 5 is the same or various substituents from the series hydrogen, halogen, cyano, nitro, trifluoromethyl, (C₁-C₆) alkyl, (C₁- C₆) hydroxyalkyl, (C₁-C₆) alkoxy, -O- [CH₂] x C f H ( 2f + 1-g) F g , -OCF₂Cl, -O-CF₂-CHFCl, (C₁-C₆) alkylmercapto, (C₁-C₆) alkylsulfinyl, (C₁-C₆) alkylsulfonyl, (C₁-C₆) alkylcarbonyl , (C₁-C₆) alkoxycarbonyl, carbamoyl, N- (C₁-C₄) alkylcarbamoyl, N, N-di- (C₁-C₄) alkylcarbamoyl, (C₁-C₆) alkylcarbonyloxy, (C₃-C₈) cycloalkylcarbamoyl , Phenyl, benzyl, phenoxy, benzyloxy, NR 'R'', phenylmercapto, phenylsulfonyl, phenylsulfinyl, sulfamoyl, N- (C₁-C₄) alkylsulfamoyl or N, N-di- (C₁-C₄) alkylsulfamoyl, or optionally up to 3 of the above-mentioned identical or different substituents carries and two adjacent C atoms of the aralkyloxy group together carry a chain - [CH₂-] and / or -CH = CH- CH = CH-, a CH₂ group of the chain optionally being substituted by O, S, SO, SO₂ or NR ' is replaced.

R¹ und R² oder R² und R³ können eine Kette [CH₂]o bilden, wobei o = 3, 4 oder 5 bedeutet, oder
einen, gegebenenfalls mit Fluor, Chlor (C₁-C₈)-Alkoxy oder einem Carbamoyl- Rest substituierten, carbocyclischen 6gliedrigen aromatischen Ring bilden.R¹ and R² or R² and R³ can form a chain [CH₂] o , where o = 3, 4 or 5, or
form a, optionally substituted with fluorine, chlorine (C₁-C₈) alkoxy or a carbamoyl radical, carbocyclic 6-membered aromatic ring.

Vorzugsweise bilden die Substituenten R¹ und R² oder R² und R³ zusammen mit dem sie tragenden Pyridin bzw. Pyridazin einen Cinnolin-, einen Chinolin- oder einen Isochinolin-Ring.Preferably the substituents R¹ and R² or R² and R³ together form the pyridine or pyridazine carrying it is a cinnoline, a quinoline or an isoquinoline ring.

R⁴ bedeutet vorzugsweise einen verzweigten oder unverzweigten (C₁-C₂₀)- Alkylrest, der bis zu 3 C-C-Mehrfachbindungen enthalten kann, (C₁-C₁₂)- Alkoxy-(C₁-C₈)-alkyl, (C₁-C₁₂)-Alkoxy-(C₁-C₈)-alkoxy-(C₁-C₈)-alkyl, [CH₂]x CfH(2f+1-g)Fg, oder (C₆-C₁₂)-Aryl, (C₇-C₁₁)-Aralkyl, Heteroaryl, Heteroaralkyl, (C₃-C₈)-Cycloalkyl, (C₃-C₈)-Cycloalkyl-(C₁-C₆)-alkyl, (C₆- C₁₄)-Aryloxy-(C₁-C₈)-alkyl, Heteroaryloxy-(C₁-C₈)-alkyl, (C₃-C₈)- Cycloalkyloxy-(C₁-C₈)-alkyl, (C₇-C₁₆)-Aralkyloxy-(C₁-C₈)-alkyl, Heteroaralkyloxy-(C₁-C₈)-alkyl,
(C₆-C₁₄)-Aryloxy-(C₁-C₈)-alkoxy-(C₁-C₈)-alkyl, Heteroalkyl-(C₁-C₈)-alkoxy-(C₁-C₈)-alkyl, (C₃-C₈)-Cycloalkoxy-(C₁-C₈)- alkoxy-(C₁-C₆)-alkyl,
(C₇-C₁₆)-Aralkyloxy-(C₁-C₈)-alkoxy-(C₁-C₈)alkyl, Heteroaralkyloxy-(C₁-C₈)-alkoxy-(C₁-C₈)-alkyl, (C₃-C₈)-Cycloalkyl-(C₁-C₆)- alkoxy-(C₁-C₆)-alkyl.R⁴ preferably denotes a branched or unbranched (C₁-C₂₀) alkyl radical, which can contain up to 3 CC multiple bonds, (C₁-C₁₂) alkoxy- (C₁-C₈) alkyl, (C₁-C₁₂) alkoxy- ( C₁-C₈) alkoxy- (C₁-C₈) alkyl, [CH₂] x C f H (2f + 1-g) F g , or (C₆-C₁₂) aryl, (C₇-C₁₁) aralkyl, heteroaryl , Heteroaralkyl, (C₃-C₈) cycloalkyl, (C₃-C₈) cycloalkyl- (C₁-C₆) alkyl, (C₆- C₁₄) aryloxy- (C₁-C₈) alkyl, heteroaryloxy- (C₁-C₈) -alkyl, (C₃-C₈) - cycloalkyloxy- (C₁-C₈) alkyl, (C₇-C₁₆) aralkyloxy- (C₁-C₈) alkyl, heteroaralkyloxy- (C₁-C₈) alkyl,
(C₆-C₁₄) aryloxy- (C₁-C₈) alkoxy- (C₁-C₈) alkyl, heteroalkyl- (C₁-C₈) alkoxy- (C₁-C₈) alkyl, (C₃-C₈) cycloalkoxy- (C₁-C₈) - alkoxy- (C₁-C₆) alkyl,
(C₇-C₁₆) aralkyloxy- (C₁-C₈) alkoxy- (C₁-C₈) alkyl, heteroaralkyloxy- (C₁-C₈) alkoxy- (C₁-C₈) alkyl, (C₃-C₈) cycloalkyl- ( C₁-C₆) - alkoxy- (C₁-C₆) alkyl.

R⁴ bedeutet insbesondere einen Rest der Formel Z,R⁴ in particular denotes a radical of the formula Z,

[CH₂]v-[O]w-[CH₂]t-E (Z),[CH₂] v - [O] w - [CH₂] t -E (Z),

worin E einen substituierten Phenylrest der Formel Fwherein E is a substituted phenyl radical of the formula F

oder einen substituierten Heteroaryl-Rest, oder einen substituierten (C₃-C₈)- Cycloalkylrest,
wobei
v = 0, 1, 2, 3, 4, 5, 6 w=0, 1 und t=0, 1, 2, 3, mit der Einschränkung, daß v ungleich 0 ist, falls w=1 ist bedeutet und R⁶, R⁷, R⁸, R⁹ und R¹⁰ gleich oder verschieden sind und Wasserstoff, Halogen, Cyano, Nitro, Trifluormethyl, (C₁-C₆)-Alkyl, (C₃-C₈-Cycloalkyl, (C₁-C₆)-Alkoxy, -O-[CH2-]xCfH(2f+1-g)Fg, -OCF₂Cl, -O-CF₂-CHFCl, (C₁-C₆)- Alkylmercapto, (C₁-C₆)-Hydroxyalkyl, (C₁-C₆)-Alkoxy-(C₁-C₆)-alkoxy, (C₁-C₆)-Alkoxy-(C₁-C₆)-alkyl, (C₁-C₆)-Alkylsulfinyl, (C₁-C₆)-Alkylsulfonyl, (C₁-C₆)-Alkylcarbonyl, (C₁-C₈)-Alkoxycarbonyl, Carbamoyl, N-(C₁-C₈)- Alkylcarbamoyl, N,N-Di-(C₁-C₈)-alkylcarbamoyl, gegebenenfalls mit Fluor, Chlor, Brom, Trifluormethyl und (C₁-C₆)-Alkoxy-substituiertes (C₇-C₁₁)- Aralkylcarbamoyl, N-(C₃-C₈)-Cycloalkylcarbamoyl, N-(C₃-C₈)-Cycloalkyl- (C₁-C₄)-alkylcarbamoyl, (C₁-C₆)-Alkylcarbonyloxy, Phenyl, Benzyl, Phenoxy, Benzyloxy, NR′R′′, wie Amino, Anilino, N-Methylanilino, Phenylmercapto, Phenylsulfonyl, Phenylsulfinyl, Sulfamoyl, N-(C₁-C₈)- Alkylsulfamoyl oder N,N-Di-(C₁-C₈)-alkylsulfamoyl bedeuten, oder zwei benachbarte Substituenten gemeinsam eine Kette -[CH2-]n oder -CH = CH- CH=CH- bedeuten, wobei eine CH₂-Gruppe der Kette gegebenenfalls durch O, S, SO, SO₂ oder NR′ ersetzt ist. Bevorzugte Heteroaryl-Reste sind Picolyl und Thienylmethyl.or a substituted heteroaryl radical, or a substituted (C₃-C₈) cycloalkyl radical,
in which
v = 0, 1, 2, 3, 4, 5, 6 w = 0, 1 and t = 0, 1, 2, 3, with the restriction that v is not equal to 0 if w = 1 and R⁶, R⁷, R⁸, R⁹ and R¹⁰ are the same or different and are hydrogen, halogen, cyano, nitro, trifluoromethyl, (C₁-C₆) alkyl, (C₃-C₈-cycloalkyl, (C₁-C₆) alkoxy, -O- [CH 2- ] x C f H (2f + 1-g) F g , -OCF₂Cl, -O-CF₂-CHFCl, (C₁-C₆) alkylmercapto, (C₁-C₆) hydroxyalkyl, (C₁-C₆) alkoxy - (C₁-C₆) alkoxy, (C₁-C₆) alkoxy- (C₁-C₆) alkyl, (C₁-C₆) alkylsulfinyl, (C₁-C₆) alkylsulfonyl, (C₁-C₆) alkylcarbonyl, ( C₁-C₈) alkoxycarbonyl, carbamoyl, N- (C₁-C₈) alkylcarbamoyl, N, N-di- (C₁-C₈) alkylcarbamoyl, optionally with fluorine, chlorine, bromine, trifluoromethyl and (C₁-C₆) alkoxy -substituted (C₇-C₁₁) aralkylcarbamoyl, N- (C₃-C₈) cycloalkylcarbamoyl, N- (C₃-C₈) cycloalkyl- (C₁-C₄) alkylcarbamoyl, (C₁-C₆) alkylcarbonyloxy, phenyl, benzyl, Phenoxy, benzyloxy, NR′R ′ ′, such as amino, anilino, N- Methylanilino, phenylmercapto, phenylsulfonyl, phenylsulfinyl, sulfamoyl, N- (C₁-C₈) alkylsulfamoyl or N, N-di- (C₁-C₈) alkylsulfamoyl, or two adjacent substituents together are a chain - [CH 2- ] n or -CH = CH- CH = CH-, where a CH₂ group of the chain is optionally replaced by O, S, SO, SO₂ or NR '. Preferred heteroaryl radicals are picolyl and thienylmethyl.

Falls R¹ und/oder R³ in der Bedeutung von (C₆-C₁₂)-Aryloxy, (C₇-C₁₁)- Aralkyloxy, (C₆-C₁₂)-Aryloxy-(C₁-C₆)-alkoxy, (C₇-C₁₁)-Aralkoxy -(C₁-C₆)-alkoxy oder einem entsprechenden endständige Cycloalkyl-Gruppen enthaltenden Rest stehen, so bedeutet dieser Rest vorzugsweise einen Rest der Formel DIf R¹ and / or R³ are (C₆-C₁₂) aryloxy, (C₇-C₁₁) - Aralkyloxy, (C₆-C₁₂) aryloxy- (C₁-C₆) alkoxy, (C₇-C₁₁) aralkoxy - (C₁-C₆) alkoxy or a corresponding radical containing terminal cycloalkyl groups are, this radical is preferably a radical of the formula D.

OZ (D),OZ (D),

wobei Z in der Bedeutung steht wie für R⁴ definiert.where Z is as defined for R⁴.

Falls R¹ und/oder R³ in der Bedeutung von (C₇-C₁₁)-Aralkyl, (C₆-C₁₂)-Aryloxy-(C₁-C₆)-alkyl, (C₇-C₁₁)-Aralkoxy-(C₁-C₆)-alkyl oder einem entsprechenden endständige Cycloalkyl-Gruppen enthaltenden Rest stehen, so bedeutet dieser Rest vorzugsweise einen Rest der Formel Z, wobei Z in der Bedeutung steht wie für R⁴ definiert.If R¹ and / or R³ are (C₇-C₁₁) aralkyl, (C₆-C₁₂) aryloxy- (C₁-C₆) alkyl, (C₇-C₁₁) aralkoxy- (C₁-C₆) alkyl or one corresponding radical containing terminal cycloalkyl groups, so this radical preferably denotes a radical of the formula Z, where Z in the Meaning stands as defined for R⁴.

R′ und R′′ sind gleich oder verschieden und bedeuten Wasserstoff, (C₆-C₁₂)- Aryl, (C₁-C₁₀)-Alkyl, (C₃-C₁₀)-Cycloalkyl, (C₁-C₈)-Alkoxy-(C₁-C₈)alkyl, (C₇-C₁₂)-Aralkoxy-(C₁-C₈)alkyl, (C₆-C₁₂)-Aryloxy-(C₁-C₈)-alkyl, (C₁-C₁₀)- Alkanoyl, ggf. substituiertes (C₇-C₁₆)-Aralkanoyl, ggf. substituiertes (C₆-C₁₂)-Aroyl, oder
R′ und R′′ stehen gemeinsam für -[CH₂]h-, worin eine CH₂-Gruppe durch O, S, N-(C₁-C₄)-Alkanoylimino oder N-(C₁-C₄)-Alkoxycarbonylimino ersetzt sein kann, undR 'and R''are the same or different and are hydrogen, (C₆-C₁₂) aryl, (C₁-C₁₀) alkyl, (C₃-C₁₀) cycloalkyl, (C₁-C₈) alkoxy- (C₁-C₈ ) alkyl, (C₇-C₁₂) aralkoxy- (C₁-C₈) alkyl, (C₆-C₁₂) aryloxy- (C₁-C₈) alkyl, (C₁-C₁₀) alkanoyl, optionally substituted (C₇-C₁₆) Aralkanoyl, optionally substituted (C₆-C₁₂) aroyl, or
R 'and R''together represent - [CH₂] h- , in which a CH₂ group can be replaced by O, S, N- (C₁-C₄) alkanoylimino or N- (C₁-C₄) alkoxycarbonylimino, and

f = 1 bis 8,
g = 0, 1 bis (2f+1),
h = 3 bis 6,
x = 0 bis 3, und
n = 3 oder 4 ist.f = 1 to 8,
g = 0.1 to (2f + 1),
h = 3 to 6,
x = 0 to 3, and
n = 3 or 4.

Besonders bevorzugt sind Verbindungen der Formel I, in der Q = O,
X = O,
Y = CR³ oder V = N, falls R¹ und R² mit dem sie tragenden Ring einen Cinnolin-Ring bilden,
m = O,
A -CHR⁵-, wobei R⁵ den Substituenten des α-C-Atoms einer α-Aminosäure bedeutet, insbesondere einer natürlichen L-Aminosäure oder ihr D- Isomeres,
B = CO₂H,
R² Wasserstoff, Chlor, (C₁-C₈)-Alkoxy, Carbamoyl, N-(C₁-C₁₀)-Alkylcarbamoyl, N,N-Di-(C₁-C₈)-alkylcarbamoyl, N-(C₃-C₈)-Cycloalkylcarbamoyl, N-(C₆-C₁₂)-Phenylcarbamoyl, N-(C₇-C₁₂)- Phenylalkylcarbamoyl, N-(C₁-C₆)-Alkyl-N-(C₆-C₁₂)phenylcarbamoyl, N-(C₁-C₆)-Alkyl-(C₇-C₁₂)-Phenylalkylcarbamoyl, N-((C₁-C₆)-Alkoxy- (C₁-C₆)alkyl)carbamoyl, (C₁-C₈)-Alkoxycarbonyl, (C₃-C₈)- Cycloalkoxycarbonyl, wobei ein Phenylrest in der Weise substituiert ist wie für R¹ und R³ definiert, und einer der Reste
R¹ und R³ Wasserstoff und der andere einen Rest aus der Reihe Wasserstoff, Fluor, Chlor, (C₁-C₈)-Alkyl, (C₁-C₁₀)-Alkoxy, (C₅-C₆)-Cycloalkyl, (C₅-C₆)-Cycloalkyl-(C₁-C₆)-alkyl, (C₅-C₆)-Cycloalkyloxy, (C₅-C₆)- Cycloalkyl-(C₁-C₆)-alkoxy, (C₅-C₆)-Cycloalkyloxy-(C₁-C₆)-alkyl, (C₅- C₆)-Cycloalkyloxy-(C₁-C₆)-alkoxy, (C₅-C₆)-Cycloalkyl-(C₁-C₄)-alkyl- (C₁-C₄)-alkoxy, (C₅-C₆)-Cycloalkyl-(C₁-C₄)-alkoxy-(C₁-C₂)-alkyl, (C₅-C₆)-Cycloalkoxy-(C₁-C₄)-alkoxy-(C₁-C₂)-alkyl, -O-[CH₂]x- CfH(2f+1-g)Fg, -NR′R′′, (C₁-C₆)-Alkoxy-(C₁-C₆)-alkyl, (C₁-C₆)- Alkoxy-(C₁-C₆)-alkoxy, (C₁-C₆)-Alkoxy-(C₁-C₄)-alkoxy-(C₁-C₂)-alkyl, substituiertes (C₆-C₁₂)-Phenoxy, (C₇-C₁₁)-Phenylalkyloxy, (C₆-C₁₂)- Phenoxy-(C₁-C₆)-alkoxy oder (C₇-C₁₁)-Phenylalkoxy-(C₁-C₆)-alkoxy, Phenoxy-(C₁-C₄)-alkyl, (C₇-C₁₁)-Phenyl(alkyloxy-(C₁-C₄)-alkyl, Phenoxy-(C₁-C₄)-alkoxy-(C₁-C₂)-alkyl, (C₇-C₁₁)-Phenylalkyloxy- (C₁-C₄)-alkoxy-(C₁-C₂)-alkyl bedeutet, wobei ein aromatischer Rest mit 1, 2 oder 3 gleichen oder verschiedenen Substituenten aus der Reihe Fluor, Chlor, Brom, Cyano, Trifluormethyl, (C₁-C₆)-Alkyl, (C₁-C₆)-Alkoxy, substituiert ist, oder
R¹ und R² bilden mit dem sie tragenden Pyridin einen 5,6,7,8- Tetrahydroisochinolin-Ring, oder
bilden einen, gegebenenfalls substituierten, carbocyclischen 6gliedrigen aromatischen Ring, wobei R¹ und R² mit dem sie tragenden Pyridin bzw. Pyridazin für ein Isochinolin- bzw. einen Cinnolin-Ring stehen,
R⁴ einen verzweigten oder unverzweigten (C₁-C₂₀)-Alkylrest, der eine oder zwei C-C-Mehrfachbindungen enthalten kann, oder
(C₁-C₈)-Alkoxy-(C₁-C₆)-alkyl, (C₁-C₆)-Alkoxy-(C₁-C₄)-alkoxy-(C₁-C₄)alkyl
oder einen Rest der Formel Z bedeutet,Compounds of the formula I in which Q = O,
X = O,
Y = CR³ or V = N, if R¹ and R² form a cinnolin ring with the ring carrying them,
m = O,
A -CHR⁵-, where R⁵ is the substituent of the α-C atom of an α-amino acid, in particular a natural L-amino acid or its D isomer,
B = CO₂H,
R² is hydrogen, chlorine, (C₁-C₈) alkoxy, carbamoyl, N- (C₁-C₁₀) alkylcarbamoyl, N, N-di- (C₁-C₈) alkylcarbamoyl, N- (C₃-C₈) cycloalkylcarbamoyl, N - (C₆-C₁₂) phenylcarbamoyl, N- (C₇-C₁₂) - phenylalkylcarbamoyl, N- (C₁-C₆) alkyl-N- (C₆-C₁₂) phenylcarbamoyl, N- (C₁-C₆) alkyl- (C₇ -C₁₂) phenylalkylcarbamoyl, N - ((C₁-C₆) alkoxy- (C₁-C₆) alkyl) carbamoyl, (C₁-C₈) alkoxycarbonyl, (C₃-C₈) - cycloalkoxycarbonyl, a phenyl radical being substituted in the manner as defined for R¹ and R³, and one of the residues
R¹ and R³ are hydrogen and the other is a radical from the series consisting of hydrogen, fluorine, chlorine, (C₁-C₈) alkyl, (C₁-C₁₀) alkoxy, (C₅-C₆) cycloalkyl, (C₅-C₆) cycloalkyl- (C₁-C₆) alkyl, (C₅-C₆) cycloalkyloxy, (C₅-C₆) - cycloalkyl- (C₁-C₆) alkoxy, (C₅-C₆) cycloalkyloxy- (C₁-C₆) alkyl, (C₅ - C₆) Cycloalkyloxy- (C₁-C₆) alkoxy, (C₅-C₆) cycloalkyl- (C₁-C₄) alkyl- (C₁-C₄) alkoxy, (C₅-C₆) cycloalkyl- (C₁-C₄ ) -alkoxy- (C₁-C₂) -alkyl, (C₅-C₆) -cycloalkoxy- (C₁-C₄) -alkoxy- (C₁-C₂) -alkyl, -O- [CH₂] x - C f H (2f + 1-g) F g , -NR'R '', (C₁-C₆) alkoxy- (C₁-C₆) alkyl, (C₁-C₆) - alkoxy- (C₁-C₆) alkoxy, (C₁-C₆ ) Alkoxy- (C₁-C₄) alkoxy- (C₁-C₂) alkyl, substituted (C₆-C₁₂) phenoxy, (C₇-C₁₁) phenylalkyloxy, (C₆-C₁₂) - phenoxy- (C₁-C₆) -alkoxy or (C₇-C₁₁) -phenylalkoxy- (C₁-C₆) -alkoxy, phenoxy- (C₁-C₄) -alkyl, (C₇-C₁₁) -phenyl (alkyloxy- (C₁-C₄) -alkyl, phenoxy- ( C₁-C₄) alko xy- (C₁-C₂) alkyl, (C₇-C₁₁) -phenylalkyloxy- (C₁-C₄) -alkoxy- (C₁-C₂) -alkyl means, an aromatic radical having 1, 2 or 3 identical or different substituents the series fluorine, chlorine, bromine, cyano, trifluoromethyl, (C₁-C₆) alkyl, (C₁-C₆) alkoxy, is substituted, or
R¹ and R² form a 5,6,7,8-tetrahydroisoquinoline ring with the pyridine bearing them, or
form an optionally substituted, carbocyclic 6-membered aromatic ring, R¹ and R² together with the pyridine or pyridazine carrying them being an isoquinoline or a cinnoline ring,
R⁴ is a branched or unbranched (C₁-C₂₀) alkyl radical which may contain one or two CC multiple bonds, or
(C₁-C₈) alkoxy- (C₁-C₆) alkyl, (C₁-C₆) alkoxy- (C₁-C₄) alkoxy- (C₁-C₄) alkyl
or represents a radical of the formula Z,

-[CH₂]v-[O]w-[CH₂]t-E (Z),- [CH₂] v - [O] w - [CH₂] t -E (Z),

wobei E einen substituierten Phenylrest der Formel Fwhere E is a substituted phenyl radical of the formula F

oder einen (C₃-C₈)-Cycloalkylrest bedeutet, wobei
v = 0, 1, 2, 3, w = 0, 1 und t = 0, 1 sein kann, mit der Einschränkung, daß v ungleich 0 ist, falls w = 1 ist, und worin R⁶, R⁷, R⁸, R⁹ und R¹⁰ gleich oder verschieden sind und Wasserstoff, Fluor, Chlor, Cyano, Trifluormethyl, (C₁-C₆)-Alkyl, (C₁-C₆)- Alkoxy, -O-[CH2-]xCfH(2f+1-g)Fg, N-(C₁-C₈)-Alkylcarbamoyl, N,N-Di-(C₁- C₈)-alkylcarbamoyl, N-(C₃-C₈)-Cycloalkylcarbamoyl, gegebenenfalls mit Fluor, Chlor, Trifluormethyl und (C₁-C₆)-Alkoxy substituiertes (C₇-C₁₁)- Phenylalkylcarbamoyl bedeuten.or a (C₃-C₈) cycloalkyl radical, where
v = 0, 1, 2, 3, w = 0, 1 and t = 0, 1, with the restriction that v is not equal to 0 if w = 1, and wherein R⁶, R⁷, R⁸, R⁹ and R¹⁰ are the same or different and are hydrogen, fluorine, chlorine, cyano, trifluoromethyl, (C₁-C₆) alkyl, (C₁-C₆) alkoxy, -O- [CH 2- ] x C f H (2f + 1-g ) F g , N- (C₁-C₈) alkylcarbamoyl, N, N-di- (C₁- C₈) alkylcarbamoyl, N- (C₃-C₈) cycloalkylcarbamoyl, optionally with fluorine, chlorine, trifluoromethyl and (C₁-C₆ ) -Alkoxy substituted (C₇-C₁₁) - phenylalkylcarbamoyl mean.

Falls R¹ oder R³ in der Bedeutung von (C₆-C₁₂)-Phenoxy, (C₇-C₁₁)- Phenylalkyloxy, (C₆-C₁₂)-Phenoxy-(C₁-C₆)-alkoxy, (C₇-C₁₁ )-Phenylalkoxy- (C₁-C₆)-alkoxy, (C₅-C₆)-Cycloalkyloxy, (C₅-C₆)-Cycloalkyl-(C₁ -C₆)-alkoxy, (C₅- C₆)-Cycloalkoxy-(C₁-C₆)-alkoxy oder (C₅-C₆)-Cycloalkyl-(C₁-C₄)-alkyl-(C₁-C₄)- alkoxy steht, so bedeutet dieser Rest im speziellen einen Rest der Formel DIf R¹ or R³ has the meaning of (C₆-C₁₂) phenoxy, (C₇-C₁₁) - Phenylalkyloxy, (C₆-C₁₂) phenoxy- (C₁-C₆) alkoxy, (C₇-C₁₁) phenylalkoxy- (C₁-C₆) alkoxy, (C₅-C₆) cycloalkyloxy, (C₅-C₆) cycloalkyl- (C₁ -C₆) alkoxy, (C₅- C₆) -cycloalkoxy- (C₁-C₆) -alkoxy or (C₅-C₆) -cycloalkyl- (C₁-C₄) -alkyl- (C₁-C₄) - alkoxy, this radical means in particular a radical of the formula D.

OZ (D),OZ (D),

wobei Z in der Bedeutung steht wie unter R⁴ definiert.where Z is as defined under R⁴.

Falls R¹ oder R³ in der Bedeutung von Phenyl, Phenoxy-(C₁-C₆)-alkyl, (C₇-C₁₁)- Phenylalkyl, (C₇-C₁₁)-Phenylalkyloxy-(C₁-C₄)-alkyl, (C₅-C₆)-Cycloalkyl, (C₅-C₆)- Cycloalkyl-(C₁-C₆)-alkyl, (C₅-C₆)-Cycloalkoxy-(C₁-C₄)-alkyl, (C₅-C₆)-Cycloalkyl- (C₁-C₄)-alkoxy-(C₁-C₂)-alkyl, (C₅-C₆)-Cycloalkoxy-(C₁-C₄)-alkoxy-(C₁-C₂)-alkyl, steht, so bedeutet dieser Rest im speziellen einen Rest der Formel Z worinIf R¹ or R³ is phenyl, phenoxy- (C₁-C₆) alkyl, (C₇-C₁₁) - Phenylalkyl, (C₇-C₁₁) phenylalkyloxy- (C₁-C₄) alkyl, (C₅-C₆) cycloalkyl, (C₅-C₆) - Cycloalkyl- (C₁-C₆) alkyl, (C₅-C₆) cycloalkoxy- (C₁-C₄) alkyl, (C₅-C₆) cycloalkyl- (C₁-C₄) alkoxy- (C₁-C₂) alkyl, (C₅-C₆) cycloalkoxy- (C₁-C₄) alkoxy- (C₁-C₂) alkyl, stands, this radical means in particular a radical of the formula Z.  wherein

v = 1, 2, 3 und 4, w = 0 und t = 0 oder
v = 1, 2, 3 und 4, w = 1 und t = 0 oder
v = 1, 2, 3 und 4, w = 1, t = 1 sind
und Z in der Bedeutung steht wie unter R⁴ definiert.v = 1, 2, 3 and 4, w = 0 and t = 0 or
v = 1, 2, 3 and 4, w = 1 and t = 0 or
v = 1, 2, 3 and 4, w = 1, t = 1
and Z has the meaning as defined under R⁴.

Die Erfindung umfaßt weiterhin Prodrugs zu den Verbindungen der Formel (I), die eine Hemmung der Kollagenbiosynthese in vivo durch Freisetzung von Verbindungen der Formel I oder deren Salzen bewirken.The invention further comprises prodrugs for the compounds of the formula (I) which inhibit collagen biosynthesis in vivo by releasing Effect compounds of formula I or their salts.

Schließlich umfaßt die Erfindung auch Prodrugs, die in vivo durch Freisetzung von Verbindungen der Formel I oder deren Salzen eine inhibitorische Wirkung auf die Prolyl-4-hydroxylase bewirken.Finally, the invention also encompasses prodrugs released in vivo of compounds of formula I or their salts have an inhibitory effect on the prolyl 4-hydroxylase.

Prodrug-Gruppierungen sind chemische Gruppen, die in vivoProdrug groupings are chemical groups that are in vivo

  • - zur Carboxylatgruppe der Verbindungen der Formel I umgewandelt werden und/oder- Converted to the carboxylate group of the compounds of formula I. be and / or
  • - vom Amid-N-Atom abgespalten werden können und/oder- Can be split off from the amide N atom and / or
  • - zu einem Pyridinring umgewandelt werden können.- Can be converted to a pyridine ring.

Die in Betracht kommenden Prodrug-Gruppen sind dem Fachmann bekannt.The prodrug groups in question are known to the person skilled in the art.

Insbesondere sind folgende Prodrug-Gruppierungen genannt:
für die Carboxylatgruppe Ester-, Amid-, Hydroxymethyl- und Aldehydgruppen und deren Abkömmlinge für das Pyridin-N-Atom N-Oxide und N-Alkylderivate und für den Pyridinring 1,4-Dihydropyridin-Derivate.The following prodrug groups are mentioned in particular:
for the carboxylate group ester, amide, hydroxymethyl and aldehyde groups and their derivatives for the pyridine N atom, N-oxides and N-alkyl derivatives and for the pyridine ring 1,4-dihydropyridine derivatives.

Die Erfindung betrifft die Verwendung von Verbindungen der allgemeinen Formel I sowie die physiologisch verträglichen Salze zur Inhibierung der Kollagenbiosynthese. The invention relates to the use of compounds of the general formula I and the physiologically tolerable salts for inhibiting the Collagen biosynthesis.  

Weiterhin betrifft die Erfindung die Verwendung von Verbindungen der allgemeinen Formel I sowie die physiologisch verträglichen Salze zur Herstellung eines Arzneimittels gegen fibrotische Erkrankungen.The invention further relates to the use of compounds of general formula I and the physiologically tolerable salts for the preparation a medicine for fibrotic diseases.

Schließlich betrifft die Erfindung die Verbindungen der allgemeinen Formel I zur Verwendung als Arzneimittel.Finally, the invention relates to the compounds of general formula I for Use as a medicine.

Insbesondere betrifft die Erfindung die Verbindungen der Formel I zur Anwendung als Fibrosuppressiva.In particular, the invention relates to the compounds of formula I for Use as a fibrosuppressant.

Weiterhin betrifft die Erfindung ein Verfahren zur Herstellung von Verbindungen der allgemeinen Formel I.The invention further relates to a method for producing compounds of the general formula I.

Die Herstellung der Verbindungen der Formel I, in denen A einen substituierten Alkylen-Teil, B = CO₂H, Y = CR³ und m = 0 und 1 bedeuten erfolgt, indemThe preparation of the compounds of formula I in which A is a substituted one Alkylene part, B = CO₂H, Y = CR³ and m = 0 and 1 mean by

  • i1.) Pyridin-2-carbonsäuren der Formel II (R¹¹ = H) mit den Aminoestern der Formel III zu den Amidestern der Formel IV umgesetzt werden, oderi1.) Pyridine-2-carboxylic acids of formula II (R¹¹ = H) with the amino esters of Formula III are implemented to the amide esters of formula IV, or
  • i2.) Pyridin-2-carbonsäureester der Formel II (R¹¹ = niedrig Alkyl) unter den Bedingungen der Aminolyse zu den Verbindungen der Formel IV umgesetzt werden; undi2.) Pyridine-2-carboxylic acid ester of the formula II (R¹¹ = low alkyl) among the Aminolysis conditions for the compounds of the formula IV be implemented; and
  • ii) die Verbindungen der Formel I aus ihren Estern der Formel IV freigesetzt werden; wobei ggf.ii) the compounds of the formula I are released from their esters of the formula IV become; where possibly
  • iii) die Verbindungen der Formel IV durch Alkylierung von Verbindungen der Formel V mit R⁴X hergestellt sind und ggf.iii) the compounds of formula IV by alkylation of compounds of Formula V are made with R⁴X and if necessary
  • iv) die Verbindungen der Formel I sofern Q = O und NR′ gilt, in ihre Pyridin- N-oxide übergeführt werden.iv) the compounds of formula I insofar as Q = O and NR 'applies in their pyridine N-oxides are transferred.

Schema 1 Scheme 1

R¹¹ = H, (C₁-C₃)-Alkyl, PG
R¹² = H, (C₁-C₃)-Alkyl
X = Abgangsgruppe, insbesondere Halogen, OSO₂Me, OSO₂PhenylR¹¹ = H, (C₁-C₃) alkyl, PG
R¹² = H, (C₁-C₃) alkyl
X = leaving group, especially halogen, OSO₂Me, OSO₂Phenyl

Geeignete Verfahren zur Amidbildung (Umsetzung i1) sind die Methoden der Carbonylaktivierung und die aus der Peptidchemie bekannten Kondensationsreaktionen.Suitable methods for amide formation (implementation i1) are the methods of Carbonyl activation and those known from peptide chemistry Condensation reactions.

An Reagenzien zur Carbonsäureaktivierung können die dem Fachmann bekannten Substanzen, wie Thionylchlorid, Oxalylchlorid, Pivaloylchlorid, Chlorameisensäureester-Derivate oder N,N′-Carbonyldimidazol Verwendung finden. Die aktivierten Derivate der Verbindungen der Formel II werden nach Herstellung in situ mit den Amidderivaten der Formel III umgesetzt.The person skilled in the art can use reagents for carboxylic acid activation known substances, such as thionyl chloride, oxalyl chloride, pivaloyl chloride, Chloroformic acid ester derivatives or N, N'-carbonyldimidazole use Find. The activated derivatives of the compounds of formula II are after Production implemented in situ with the amide derivatives of the formula III.

Ein geeignetes Kondensationsmittel ist beispielsweise die Kombination von N,N′-Dicyclohexylcarbodiimid/N-Hydroxy-1H-benzotriazol und N-Ethylmorpholin.A suitable condensing agent is, for example, the combination of N, N'-dicyclohexylcarbodiimide / N-hydroxy-1H-benzotriazole and N-ethylmorpholine.

Geeignete Lösungsmittel sind Dichlormethan, Tetrachlormethan, Butylacetat, Ethylacetat, Toluol, Tetrahydrofuran, Dimethoxyethan, 1,4-Dioxan, Acetonitril, N,N-Dimethylformamid, N,N-Dimethylacetamid, Dimethylsulfoxid, Nitromethan und/oder Pyridin.Suitable solvents are dichloromethane, carbon tetrachloride, butyl acetate, Ethyl acetate, toluene, tetrahydrofuran, dimethoxyethane, 1,4-dioxane, acetonitrile, N, N-dimethylformamide, N, N-dimethylacetamide, dimethyl sulfoxide, nitromethane and / or pyridine.

Zur Herstellung von in 4-Position substituierten Derivaten (R¹) können die aus EP-A-0 304 732, EP-A-0 321 385 und EP-A-0 208 452 bekannten 2-Hydroxymethylpyridine der Formel VIa als Zwischenprodukte Verwendung finden.To prepare derivatives substituted in the 4-position (R¹), the from EP-A-0 304 732, EP-A-0 321 385 and EP-A-0 208 452 2-hydroxymethylpyridines of the formula VIa used as intermediates Find.

Wie dort beschrieben, wurden in analoger Weise auch die 3-O-Benzylderivate der Formel VIb erhalten.As described there, the 3-O-benzyl derivatives were also used in an analogous manner of the formula VIb.

Die Verbindungen der Formeln VIa und VIb wurden mit einem Oxidationsmittel, vorzugsweise mit KMnO₄ in wäßrigem alkalischen Milieu, zu den Pyridin-2- carbonsäurederivaten der Formel II umgesetzt.The compounds of the formulas VIa and VIb were treated with an oxidizing agent, preferably with KMnO₄ in an aqueous alkaline medium, to the pyridine-2- carboxylic acid derivatives of the formula II implemented.

Die Herstellung von substituierten Pyridin-2-carbonsäuren ist beispielsweise aus DE-A-3 53 046 und für 3-(3-Chlorphenoxy)pyridin-2-carbonsäure und 3-(3- Methylphenoxy)pyridin-2-carbonsäure aus J. Med. Chem. 1975, 18, S. 1-8 , Villani et al.; 3,5.Diethoxypyridin-2-carbonsäure aus J. Med. Chem. 1974, 17, S. 172-181, French et al., sowie für 3-Methylthio- und 3-Benzylthiopyridin-2-carbonsäure aus J. Med. Chem. 1974, 17, S. 1065-1071, Blank et al. und 3-Methoxypyridin- 2,5-dicarbonsäure aus CH-PS 658 651 bekannt.The production of substituted pyridine-2-carboxylic acids is, for example, from DE-A-3 53 046 and for 3- (3-chlorophenoxy) pyridine-2-carboxylic acid and 3- (3- Methylphenoxy) pyridine-2-carboxylic acid from J. Med. Chem. 1975, 18, pp. 1-8, Villani et al .; 3,5. Diethoxypyridine-2-carboxylic acid from J. Med. Chem. 1974, 17, pp. 172-181, French et al., And for 3-methylthio- and 3-benzylthiopyridine-2-carboxylic acid J. Med. Chem. 1974, 17, pp. 1065-1071, Blank et al. and 3-methoxypyridine 2,5-dicarboxylic acid from CH-PS 658 651 known.

Die erfindungsgemäßen Verbindungen der Formel I besitzen wertvolle pharmakologische Eigenschaften und zeigen insbesondere antifibrotische Wirksamkeit.The compounds of formula I according to the invention have valuable pharmacological properties and in particular show antifibrotic Effectiveness.

Die antifibrotische Wirkung kann im Modell der Tetrachlorkohlenstoff-induzierten Leberfibrose bestimmt werden. Dazu werden Ratten mit CCl₄ (1 ml/kg) - gelöst in Olivenöl - zweimal wöchentlich behandelt. Die Prüfsubstanz wird täglich, gegebenenfalls sogar zweimal täglich per os oder intraperitoneal - gelöst in einem geeigneten verträglichen Lösungsmittel - verabreicht. Das Ausmaß der Leberfibrose wird histologisch bestimmt und der Anteil Kollagen in der Leber per Hydroxyprolinbestimmung - wie bei Kivirikko et al. (Anal. Biochem. 19, 249 f. (1967)) beschrieben - analysiert. Die Aktivität der Fibrogenese kann durch radioimmunologische Bestimmung von Kollagenfragmenten und Prokollagenpeptiden im Serum bestimmt werden. Die erfindungsgemäßen Verbindungen sind in diesem Modell in Konzentration 1 bis 100 mg/kg wirksam.The antifibrotic effect can be induced in the carbon tetrachloride model Liver fibrosis can be determined. For this, rats are dissolved with CCl₄ (1 ml / kg) in olive oil - treated twice a week. The test substance is possibly even twice a day by os or intraperitoneally - dissolved in a suitable compatible solvent. The extent of Liver fibrosis is determined histologically and the percentage of collagen in the liver per Hydroxyproline determination - as in Kivirikko et al. (Anal. Biochem. 19, 249 f. (1967)) - analyzed. The activity of fibrogenesis can be caused by radioimmunological determination of collagen fragments and  Procollagen peptides can be determined in serum. The invention Compounds are effective in this model in concentrations of 1 to 100 mg / kg.

Die Aktivität der Fibrogenese kann durch radioimmunologische Bestimmung des N-terminalen Propeptids des Kollagen Typ-III oder der N- bzw. C-terminalen Quervernetzungsdomäne des Kollagen-Typ-IV (7s-Kollagen bzw. Typ-IV-Kollagen NC₁) im Serum bestimmt werden.The activity of fibrogenesis can be determined by radioimmunological determination of the N-terminal propeptide of type III collagen or the N- or C-terminal Cross-linking domain of collagen type IV (7s collagen or type IV collagen NC₁) can be determined in the serum.

Zu diesem Zweck wurden die Hydroxyprolin-, Prokollagen-III-Peptid-, 7s- Kollagen- und Typ-IV-Kollagen-NC-Konzentrationen in der Leber vonFor this purpose the hydroxyproline, procollagen III peptide, 7s Collagen and type IV collagen NC concentrations in the liver of

  • a) unbehandelten Ratten (Kontrolle)a) untreated rats (control)
  • b) Ratten, denen Tetrachlorkohlenstoff verabreicht wurden (CCl₄-Kontrolle)b) rats to which carbon tetrachloride was administered (CCl₄ control)
  • c) Ratten, denen zunächst CCl₄ und anschließend eine erfindungsgemäße Verbindung verabreicht wurdec) rats, which first CCl₄ and then an inventive Compound was administered

gemessen (diese Testmethode wird beschrieben von Rouiller, C., experimental toxic injury of the liver; in The Liver, C. Rouiller, Vol. 2, 5. 335 bis 476, New York, Academic Press, 1964).measured (this test method is described by Rouiller, C., experimental toxic injury of the liver; in The Liver, C. Rouiller, Vol. 2, 5, 335 to 476, New York, Academic Press, 1964).

Die Verbindungen der Formel I können als Medikamente in Form pharmazeutischer Präparate Verwendung finden, welche sie gegebenenfalls mit verträglichen pharmazeutischen Trägern enthalten. Die Verbindungen können als Heilmittel, z. B. in Form pharmazeutischer Präparate Verwendung finden, welche diese Verbindungen in Mischung mit einem für die enterale, perkutane oder parenterale Applikation geeigneten pharmazeutischen, organischen oder anorganischen Träger, wie z. B. Wasser, Gummi arabicum, Gelatine, Milchzucker, Stärke, Magnesiumstearat, Talk, pflanzliche Öle, Polyalkylenglykole, Vaseline usw. enthalten.The compounds of formula I can be in the form of drugs pharmaceutical preparations are used, which they may be used with compatible pharmaceutical carriers. The connections can be made as Remedies, e.g. B. find use in the form of pharmaceutical preparations these compounds mixed with one for enteral, percutaneous or parenteral application of suitable pharmaceutical, organic or inorganic carriers, such as. B. water, gum arabic, gelatin, Milk sugar, starch, magnesium stearate, talc, vegetable oils, Contain polyalkylene glycols, petroleum jelly, etc.

Sie können zu diesem Zweck oral in Dosen von 0,1 bis 25 mg/kg/Tag, vorzugsweise 1 bis 5 mg/kg/Tag oder parenteral in Dosen von 0,01 bis 5 mg/kg/Tag, vorzugsweise 0,01 bis 2,5 mg/kg/Tag, insbesondere 0,5 bis 1,0 mg/kg/Tag, appliziert werden. Die Dosierung kann in schweren Fällen auch erhöht werden. In vielen Fällen genügen jedoch auch geringere Dosen. Diese Angaben beziehen sich auf einen Erwachsenen von etwa 75 kg Gewicht.For this purpose you can take orally in doses of 0.1 to 25 mg / kg / day, preferably 1 to 5 mg / kg / day or parenterally in doses of 0.01 to 5 mg / kg / day, preferably 0.01 to 2.5 mg / kg / day, in particular 0.5 to 1.0 mg / kg / day. The dosage can also be severe  increase. In many cases, however, lower doses are sufficient. These Figures refer to an adult weighing approximately 75 kg.

Beispiel 1example 1 3-Methoxy-4-(2,2,2-trifluorethyloxy)pyridin-2-carbonsäure-glycylamid-3-methoxy-4- (2,2,2-trifluoroethyloxy) pyridine-2-carboxylic acid glycylamide a) 2-Methyl-3-methoxy-4-chlorpyridin-N-oxida) 2-Methyl-3-methoxy-4-chloropyridine N-oxide

11,2 g (80,5 mmol) 3-Methoxy-2-methyl-4(1H)-pyridon wurden in 100 ml Phosphoroxychlorid 10 Stunden rückfließend erhitzt. Anschließend engte man ein, versetzte 2ml mit je 30 ml Toluol, engte wiederum ein, nahm den Rückstand in 150 ml Wasser auf, brachte mit K₂CO₃ auf pH 11, extrahierte mit Dichlormethan, wusch die organische Phase mit Wasser, trocknete und befreite vom Lösungsmittel.11.2 g (80.5 mmol) of 3-methoxy-2-methyl-4 (1H) -pyridone were added in 100 ml Phosphorus oxychloride heated to reflux for 10 hours. Then they narrowed , added 2 ml each with 30 ml toluene, constricted again, took the Residue in 150 ml of water, brought to pH 11 with K₂CO₃, extracted with Dichloromethane, washed the organic phase with water, dried and freed from the solvent.

Aus dem hellbraunen Öl (9 g) wurden mit m-Clorperbenzoesäure in Dichlormethan unter Standardbedingungen 8 g des Produktes erhalten, Fp. 88-89°C (aus Petrolether).From the light brown oil (9 g) with m-chloroperbenzoic acid in Dichloromethane obtained 8 g of the product under standard conditions, Mp 88-89 ° C (from petroleum ether).

b) 2-Methyl-3-methoxy-4-(2,2,2-trifluorethoxy)pyridin-N-oxidb) 2-methyl-3-methoxy-4- (2,2,2-trifluoroethoxy) pyridine-N-oxide

Zu 20 ml Trifluorethanol gab man bei -20°C unter Rühren und Stickstoffatomsphäre portionsweise 6,7 g Kalium-tert. Butylat. Nach Erwärmung auf 0°C wurden portionsweise 5,2 g (30 mmol) 2-Methyl-3-methoxy-4- chlorpyridin-N-oxid hinzugegeben. Man erwärmte 3 Stunden unter Rückfluß, ließ auf Raumtemperatur abkühlen, gab weitere 3,45 g Kalium-tert.Butylat zu und erwärmte 2 Stunden unter Rückfluß. Nach dem Abkühlen gab man 40 ml Wasser zum Reaktionsgemisch, extrahierte mit Dichlormethan, trocknete über MgSO₄ und befreite im Vakuum vom Lösungsmittel. Das erhaltene ölige Produkt wurde weiter umgesetzt. To 20 ml of trifluoroethanol was added at -20 ° C with stirring and Nitrogen atmosphere in portions 6.7 g of potassium tert. Butylate. After warming 5.2 g (30 mmol) of 2-methyl-3-methoxy-4- chlorpyridine-N-oxide added. The mixture was heated under reflux for 3 hours cool to room temperature, added a further 3.45 g of potassium tert-butoxide and heated under reflux for 2 hours. After cooling, 40 ml were added Water to the reaction mixture, extracted with dichloromethane, dried over MgSO₄ and freed from the solvent in vacuo. The oily product obtained was implemented further.  

c) 3-Methoxy-4-(2,2,2-trifluorethoxy)-2-hydroxymethyl-pyridinc) 3-methoxy-4- (2,2,2-trifluoroethoxy) -2-hydroxymethyl-pyridine

8 g (33,8 mmol) der vorstehenden Verbindung wurden in 16 ml Eisessig gelöst und unter Rühren bei 80°C mit 24 ml Acetanhydrid versetzt. Man erhitzte 2 Stunden auf 110°C, kühlte sodann auf 80°C ab und tropfte 40 ml Methanol zur Reaktionsmischung. Anschließend wurde im Vakuum eingeengt, der ölige Rückstand zu 75 ml 2 N methanolischer NaOH hinzugegeben und 30 Minuten gerührt. Nach Behandeln mit Aktivkohle und Filtration wurde im Vakuum eingeengt, der Rückstand mit 50 ml Wasser versetzt, mit Dichlormethan extrahiert, getrocknet (MgSO₄), eingeengt und der Rückstand mit Diisopropylether behandelt. Man erhielt 3,9 g des Produktes in Form farbloser Kristalle, Fp. 107-108°C.8 g (33.8 mmol) of the above compound was dissolved in 16 ml of glacial acetic acid and with stirring at 80 ° C with 24 ml of acetic anhydride. One heated 2 Hours to 110 ° C, then cooled to 80 ° C and 40 ml of methanol dripped to the reaction mixture. The mixture was then concentrated in vacuo, the oily Add residue to 75 ml of 2N methanolic NaOH and 30 minutes touched. After treatment with activated carbon and filtration, it was carried out in vacuo concentrated, the residue mixed with 50 ml of water, with dichloromethane extracted, dried (MgSO₄), concentrated and the residue with Treated diisopropyl ether. 3.9 g of the product were obtained in the form of colorless Crystals, mp 107-108 ° C.

d) 3-Methoxy-4-(2,2,2-trifluorethyloxy)pyridin-2-carbonsäured) 3-methoxy-4- (2,2,2-trifluoroethyloxy) pyridine-2-carboxylic acid

0,8 g (3,3 mmol) des vorstehenden Alkohols wurden in einer Lösung aus 0,3 g Kaliumhydroxid und 25 ml Wasser gelöst und unter Rühren bei 100°C, portionsweise 1 ,6 g Kaliumpermanganat zugegeben. Nach der Entfärbung wurde heiß vom gebildeten Braunstein abgesaugt, zweimal mit heißem Wasser gewaschen, i. Vak. auf 1/3 des Volumens eingeengt, mit conc. wäßriger Salzsäure auf pH 1 gestellt, i. Vak. eingeengt, der Rückstand mit wasserfreiem Ethanol behandelt und von Ungelösten abfiltriert. Aus dem Filtrat erhielt man 0,73 g Produkt, Fp. 157°C.0.8 g (3.3 mmol) of the above alcohol was in a solution of 0.3 g Potassium hydroxide and 25 ml of water dissolved and with stirring at 100 ° C, portions of 1.6 g of potassium permanganate are added. After decolorization sucked hot from the brown stone formed, twice with hot water washed, i. Vac. concentrated to 1/3 of the volume, with conc. watery Hydrochloric acid adjusted to pH 1, i. Vac. concentrated, the residue with anhydrous Treated ethanol and filtered from undissolved. One obtained from the filtrate 0.73 g product, mp 157 ° C.

e) 3-Methoxy-4-(2,2,2-trifluorethyloxy)pyridin-2-carbonsäure- (glycylethylester)amide) 3-methoxy-4- (2,2,2-trifluoroethyloxy) pyridine-2-carboxylic acid (glycyl ethyl ester) amide

0,58 g (2,3 mmol) der vorstehenden Carbonsäure wurden in 100 ml wasserfreiem Tetrahydrofuran suspendiert, bei 20°C unter Rühren mit 322 mg (2,3 mmol) Glycinethylester-Hydrochlorid, 0,64 ml (5 mmol) N-Ethylmorpholin, 350 mg (2,6 mmol) 1-Hydroxy-1H-benzotriazol, 537 mg (2,6 mmol) N,N′-Dicyclohexylcarbodiimid versetzt und 48 h bei 20°C gerührt. Dann wurde vom Ungelöstem abfiltriert, i.Vak. eingeengt, der Rückstand in Ethylacetat aufgenommen, vom Ungelöstem abfiltriert, das Filtrat mit 100 ml gesättigter wäßriger Na-bicarbonat-Lösung gerührt, die organische Phase getrocknet, i .Vak. eingeengt und der Rückstand mit Diisopropylether zur Kristallisation gebracht. Man erhielt 0,45 g des farblosen kristallinen Produkts, Fp. 80-82°C.0.58 g (2.3 mmol) of the above carboxylic acid was dissolved in 100 ml anhydrous tetrahydrofuran suspended at 20 ° C with stirring with 322 mg (2.3 mmol) glycine ethyl ester hydrochloride, 0.64 ml (5 mmol) N-ethylmorpholine, 350 mg (2.6 mmol) 1-hydroxy-1H-benzotriazole, 537 mg (2.6 mmol) N, N'-dicyclohexylcarbodiimide were added and the mixture was stirred at 20 ° C. for 48 h. Then was  filtered off from the undissolved, i.Vak. concentrated, the residue in ethyl acetate taken up, filtered off from the undissolved, the filtrate saturated with 100 ml aqueous Na bicarbonate solution stirred, the organic phase dried, i .Vak. concentrated and the residue brought to crystallization with diisopropyl ether. 0.45 g of the colorless crystalline product was obtained, mp. 80-82 ° C.

f) 0,4 g (1,2 mmol) des vorstehenden Esters wurden in 50 ml 1,5 N methanolische Natronlauge gegeben und 30 Min. bei 20°C gerührt. Dann wurde i. Vak. eingeengt, der Rückstand in 50 ml Wasser aufgenommen, mit conc. wäßriger Salzsäure auf pH 1 gebracht, von wenig Ungelöstem abfiltriert, das Filtrat i. Vak. eingeengt, der Rückstand mit 50 ml wasserfreiem Ethanol behandelt, abfiltriert, das Filtrat eingeengt und mit Diethylether zur Kristallisation gebracht. Man erhielt 0,32 g der Titelverbindung, Fp. 163-165°C (unter Gasentwicklung).f) 0.4 g (1.2 mmol) of the above ester was dissolved in 50 ml of 1.5N added methanolic sodium hydroxide solution and stirred at 20 ° C. for 30 minutes. Then was i. Vac. concentrated, the residue taken up in 50 ml of water with conc. brought aqueous hydrochloric acid to pH 1, filtered off a little undissolved, the filtrate i. Vac. concentrated, the residue with 50 ml of anhydrous ethanol treated, filtered off, the filtrate concentrated and with diethyl ether for crystallization brought. 0.32 g of the title compound, mp 163-165 ° C. (below Gas evolution).

Beispiel 2Example 2 4-Chlor-3-methoxypyridin-2-carbonsäure-glycylamid4-chloro-3-methoxypyridine-2-carboxylic acid glycylamide a) 4-Chlor-2-hydroxymethyl-3-methoxy-pyridina) 4-chloro-2-hydroxymethyl-3-methoxy-pyridine

30 g (173 mmol) 4-Chlor-3-methoxy-2-methylpyridin-N-oxid (vgl. Beispiel 1a< wurden in 100 ml Eisessig gelöst, bei 80°C unter Rühren tropfenweise mit 150 ml Acetanhydrid versetzt und 2 h bei 110°C gerührt. Dann wurde auf 80°C abgekühlt, 200 ml Methanol zugetropft, 15 min. zum Sieden erhitzt, nach Abkühlen i. Vak. eingeengt, der Rückstand in Methanol aufgenommen und in 300 ml 1,5 N methanolische Natronlauge einfließen lassen, 30 min. bei 20°C gerührt, i.Vak. eingeengt, der Rückstand in Wasser aufgenommen, dreimal mit Dichlormethan extrahiert, die organische Phase getrocknet, eingeengt und der Rückstand mit Petrolether zur Kristallisation gebracht. Man erhielt 23 g Produkt, Fp. 64-66°C. 30 g (173 mmol) of 4-chloro-3-methoxy-2-methylpyridine-N-oxide (see Example 1a < were dissolved in 100 ml of glacial acetic acid, at 80 ° C. with stirring dropwise 150 ml of acetic anhydride were added and the mixture was stirred at 110 ° C. for 2 h. Then was on Cooled 80 ° C, added dropwise 200 ml of methanol, 15 min. heated to boiling, after cooling i. Vac. concentrated, the residue taken up in methanol and allow to flow into 300 ml of 1.5 N methanolic sodium hydroxide solution, 30 min. at Stirred at 20 ° C, i.Vac. concentrated, the residue taken up in water three times extracted with dichloromethane, the organic phase dried, concentrated and the residue was crystallized with petroleum ether. 23 g were obtained Product, mp 64-66 ° C.  

b) 4-Chlor-3-methoxypyridin-2-carbonsäureb) 4-chloro-3-methoxypyridine-2-carboxylic acid

8.65 g (50 mmol) des vorstehenden Alkohols wurden in einer Mischung aus 0,8 g Kaliumhydroxid und 60 ml Wasser gelöst und bei 60°C unter Rühren portionsweise mit Kaliumpermanganat versetzt bis keine Entfärbung mehr zu sehen ist (12 g, 75 mmol). Nach 1 h bei 60°C wurde vom Braunstein abgesaugt, mit heißem Wasser nachgewaschen, das Filtrat i.Vak. auf 200 ml eingeengt und unter Kühlung mit wäßriger konz. HCl auf pH 1 gestellt. Nach Anreiben kristallisiert unter Kühlung das Produkt aus. Aus der Mutterlauge kann durch Behandeln mit Petrolether weiteres Produkt gewonnen werden, Gesamtmenge 4,2 g, Fp. 116-117°C (unter Gasentwicklung).8.65 g (50 mmol) of the above alcohol were mixed out 0.8 g of potassium hydroxide and 60 ml of water dissolved and at 60 ° C with stirring Potassium permanganate added in portions until no more discoloration can be seen (12 g, 75 mmol). After 1 h at 60 ° C from the brown stone suction filtered, washed with hot water, the filtrate i.Vac. to 200 ml concentrated and with cooling with aqueous conc. HCl adjusted to pH 1. To Rubbing crystallizes the product under cooling. From the mother liquor can further product can be obtained by treatment with petroleum ether, Total amount 4.2 g, mp 116-117 ° C (with gas evolution).

c) 4-Chlor-3-methoxypyridin-2-carbonsäure(glycylethylester)amidc) 4-chloro-3-methoxypyridine-2-carboxylic acid (glycylethyl ester) amide

4,7 g (25 mmol) der vorstehenden Carbonsäure wurden in 200 ml wasserfreiem Dichlormethan suspendiert und bei 20°C unter Rühren nacheinander mit 3,5 g (25 mmol) Glycinethylester-Hydrochlorid, 6,4 ml (50 mmol) N-Ethylmorpholin, 3,8 g (28 mmol) 1-Hydroxy-(1H)-benztriazol und 5,15 (25 mmol) N,N′- Dicyclohexylcarbodiimid versetzt und 20 h bei 20°C gerührt. Dann wurde vom Ungelösten abfiltriert, die organische Phase mit gesättigter, wäßriger Natriumcarbonat-Lösung geschüttelt, getrocknet, i.Vak. eingeengt, der Rückstand (6 g Öl) mit Ethylacetat an Kieselgel chromatographiert und 5,4 g öliges Produkt erhalten.4.7 g (25 mmol) of the above carboxylic acid were anhydrous in 200 ml Suspended dichloromethane and at 20 ° C with stirring in succession with 3.5 g (25 mmol) glycine ethyl ester hydrochloride, 6.4 ml (50 mmol) N-ethylmorpholine, 3.8 g (28 mmol) of 1-hydroxy- (1H) -benztriazole and 5.15 (25 mmol) of N, N'- Dicyclohexylcarbodiimid added and stirred at 20 ° C for 20 h. Then from Filtered undissolved, the organic phase with saturated, aqueous Sodium carbonate solution shaken, dried, in vacuo. restricted, the Residue (6 g oil) chromatographed on silica gel with ethyl acetate and 5.4 g Obtain oily product.

d) Die Titelverbindung wurde erhalten, indem der vorstehende Ethylester verseift wurde. Dazu wurden 0,7 g (2,6 mmol) dieses Esters in 50 ml Methanol/Wasser (3 : 1) gelöst und bei 20°C unter Rühren mit 170 mg (7 mmol) Lithiumhydroxid versetzt. Nach 30 min. wurde i. Vak. eingeengt; mit conc. wäßriger Salzsäure auf pH 1 gebracht, i. Vak. eingeengt, der Rückstand zweimal mit wasserfreiem Ethanol behandelt, die ethanolische Phase eingeengt, der Rückstand mit heißem Ethylacetat behandelt und der amorphe Rückstand an der Ölpumpe getrocknet. Man erhielt 0,31 g der Titelverbindung. d) The title compound was obtained by saponifying the above ethyl ester has been. 0.7 g (2.6 mmol) of this ester in 50 ml of methanol / water were added (3: 1) dissolved and at 20 ° C with stirring with 170 mg (7 mmol) lithium hydroxide transferred. After 30 min. was i. Vac. constricted; with conc. aqueous hydrochloric acid brought to pH 1, i. Vac. concentrated, the residue twice with anhydrous Treated ethanol, the ethanolic phase concentrated, the residue with hot Treated ethyl acetate and the amorphous residue dried on an oil pump. 0.31 g of the title compound was obtained.  

Beispiel 3Example 3

4-Butyloxy-3-methoxypyridin-2-carbonsäure-glycylamid Fp: 137-139°C (unter Gasentwicklung, aus Tetrahydrofuran<4-butyloxy-3-methoxypyridine-2-carboxylic acid glycylamide Mp: 137-139 ° C (with gas evolution, from tetrahydrofuran <

Beispiel 4Example 4

3,4-Dimethoxypyridin-2-carbonsäure-glycylamid3,4-dimethoxypyridine-2-carboxylic acid glycylamide

Beispiel 5Example 5

3-Ethyloxy-4-(3-methoxybenzyloxy)pyridin-2-carbonsäure-glycylamid3-ethyloxy-4- (3-methoxybenzyloxy) pyridine-2-carboxylic acid glycylamide

Beispiel 6Example 6

4-Hexyloxy-3-methoxypyridin-2-carbonsäure-glycylamid4-hexyloxy-3-methoxypyridine-2-carboxylic acid glycylamide

Beispiel 7Example 7

3-Methoxy-4-(3-methylbutyloxy)pyridin-2-carbonsäure-glycylamid3-methoxy-4- (3-methylbutyloxy) pyridine-2-carboxylic acid glycylamide

Beispiel 8Example 8

4-(4-Fluorbenzyloxy)-3-methoxypyridin-2-carbonsäure-glycylamid4- (4-fluorobenzyloxy) -3-methoxypyridine-2-carboxylic acid glycylamide

Beispiel 9Example 9

3-Methoxy-4-(4-trifluormethylbenzyloxy)pyridin-2-carbonsäure-glycyla-mid3-methoxy-4- (4-trifluoromethylbenzyloxy) pyridine-2-carboxylic acid glycyla-mid

Beispiel 10Example 10

3-Methoxy-4-(2,2,3,3,3-pentafluorpropyloxy)pyridin-2-carbonsäure-gly-cylamid3-methoxy-4- (2,2,3,3,3-pentafluoropropyloxy) pyridine-2-carboxylic acid glycylamide

Beispiel 11Example 11

4-(2,2,3,3,4,4,4-Heptafluorbutyloxy)-3-methoxypyridin-2-carbonsäure--glyclamid4- (2,2,3,3,4,4,4-heptafluorobutyloxy) -3-methoxypyridine-2-carboxylic acid - glyclamide

Beispiel 12Example 12

4-(3-Methoxybenzyloxy)-3-methoxypyridin-2-carbonsäure-glycylamid 4- (3-methoxybenzyloxy) -3-methoxypyridine-2-carboxylic acid glycylamide  

Beispiel 13Example 13

3-Ethyloxy-4-(2,2,2-trifluorethyloxy)pyridin-2-carbonsäure-glycylami-d3-Ethyloxy-4- (2,2,2-trifluoroethyloxy) pyridine-2-carboxylic acid glycylami-d

Beispiel 14Example 14

4-Butyloxy-3-ethyloxypyridin-2-carbonsäure-glycylyamid4-butyloxy-3-ethyloxypyridine-2-carboxylic acid glycylyamide

Beispiel 15Example 15

3-Methoxy-4-((2-phenoxyethyl)oxy)pyridin-2-carbonsäure-glycylamid3-methoxy-4 - ((2-phenoxyethyl) oxy) pyridine-2-carboxylic acid glycylamide

Beispiel 16Example 16

3-Ethyloxy-4-benzyloxypyridin-2-carbonsäure-glycylamid3-ethyloxy-4-benzyloxypyridine-2-carboxylic acid glycylamide

Beispiel 17Example 17

3,6-Di 19578 00070 552 001000280000000200012000285911946700040 0002004337271 00004 19459methoxypyridin-2-carbonsäure-glycylamid3,6-Di 19578 00070 552 001000280000000200012000285911946700040 0002004337271 00004 19459 methoxypyridine-2-carboxylic acid glycylamide

a) 3,6-Dimethoxy-2-methylpyridin-N-oxida) 3,6-Dimethoxy-2-methylpyridine-N-oxide

1,15 g (50 mmol) Natrium wurden in 100 ml wasserfreiem Methanol gelöst und unter Rühren bei 20°C 7,4 g (40 mmol) 3-Methoxy-2-methyl-6-nitropyridin- N-oxid hinzugegeben. Dann wurde 3 h zum Rückfluß erhitzt, nach dem Abkühlen i. Vak. eingeengt, der Rückstand in Wasser aufgenommen, mit Dichlormethan extrahiert, die organische Phase getrocknet, eingeengt und der Rückstand mit Diisopropylether zur Kristallisation gebracht. Man erhielt 7 g Produkt, Fp. 63-65°C.1.15 g (50 mmol) sodium was dissolved in 100 ml of anhydrous methanol and 7.4 g (40 mmol) of 3-methoxy-2-methyl-6-nitropyridine with stirring at 20 ° C. N-oxide added. Then was heated to reflux for 3 h, after which Cooling i. Vac. concentrated, the residue taken up in water with Extracted dichloromethane, the organic phase dried, concentrated and the Bring residue to crystallization with diisopropyl ether. 7 g were obtained Product, mp 63-65 ° C.

b) 3, 6-Dimethoxy-2-hydroxymethylpyridinb) 3, 6-Dimethoxy-2-hydroxymethylpyridine

7 g (41,4 mmol) der vorstehenden Verbindung wurden analog Beispiel 1c) mit Eisessig/Acetanhydrid umgesetzt und das erhaltene Acetat mit 1,5 N methanolischer Natronlauge verseift. Man erhielt 5,6 g öliges Produkt, das unter c) weiter umgesetzt wurde. 7 g (41.4 mmol) of the above compound were analogous to Example 1c) Glacial acetic acid / acetic anhydride and the acetate obtained with 1.5 N Saponified methanolic sodium hydroxide solution. 5.6 g of an oily product were obtained, which are stored under c) was implemented further.  

c) 3, 6.Dimethoxypyridin-2-carbonsäurec) 3, 6. Dimethoxypyridine-2-carboxylic acid

5,6 g (33 mmol) der vorstehenden Verbindung und 2,4 g Kaliumhydroxid wurden in 150 ml Wasser gelöst und bei 60°C unter Rühren portionsweise mit 15 g (100 mmol) Kaliumpermanganat versetzt. Dann wurde vom gebildeten Braunstein abgesaugt, dieser zweimal mit heißem Wasser gewaschen, die vereinigte Wasserphase auf 100 ml eingeengt, unter Eiskühlung mit conc. wäßriger Salzsäure auf pH 1 gebracht, i.Vak. eingeengt, der Rückstand mit Ethylacetat und Ethanol behandelt, vom Ungelöstem abfiltriert und i. Vak. eingeengt. Der Rückstand wurde mit Diethylether zur Kristallisation gebracht. Man erhielt 4 g Produkt, Fp. 131-132°C (unter Gasentwicklung).5.6 g (33 mmol) of the above compound and 2.4 g of potassium hydroxide were dissolved in 150 ml of water and added in portions at 60 ° C. with stirring 15 g (100 mmol) of potassium permanganate were added. Then the educated Aspirated brown stone, washed twice with hot water, the combined water phase concentrated to 100 ml, with ice cooling with conc. brought aqueous hydrochloric acid to pH 1, i.Vac. concentrated, the residue with Treated ethyl acetate and ethanol, filtered off the undissolved and i. Vac. constricted. The residue was crystallized with diethyl ether. 4 g of product were obtained, mp 131-132 ° C. (with evolution of gas).

d) 3,6-Dimethoxypyridin-2-carbonsäure-(glycylethylester)amidd) 3,6-Dimethoxypyridine-2-carboxylic acid (glycylethyl ester) amide

2,2 g (12 mmol) der vorstehenden Carbonsäure wurden in 300 ml wasserfreiem Dichlormethan suspendiert, unter Rühren mit 1,68 g (12 mmol) Glycinethylester- Hydrochlorid, 3,25 ml (25 mmol) N-Ethylmorpholin, 1,62 g (12 mmol) 1-Hydroxy-(1H)-benztriazol und 5,2 g (12 mmol) N-Cyclohexyl-N′-(2- morpholinethyl)-carbodiimid-methyl-p-toluolsulfonat versetzt und 20 h bei 20°C gerührt. Dann wurde von wenig Ungelöstem abfiltriert, einmal mit Wasser, dann mit gesättigter wäßriger Na-bicarbonat-Lösung geschüttelt, die organische Phase getrocknet, i.Vak. eingeengt und der Rückstand mit Diisopropylether zur Kristallisation gebracht. Man erhielt 2 g Produkt, Fp. 93-95°C.2.2 g (12 mmol) of the above carboxylic acid were anhydrous in 300 ml Suspended dichloromethane with 1.68 g (12 mmol) glycine ethyl ester with stirring Hydrochloride, 3.25 ml (25 mmol) N-ethylmorpholine, 1.62 g (12 mmol) 1-hydroxy- (1H) -benztriazole and 5.2 g (12 mmol) N-cyclohexyl-N ′ - (2- morpholinethyl) carbodiimide-methyl-p-toluenesulfonate added and 20 h at 20 ° C. touched. Then little undissolved matter was filtered off, once with water, then shaken with saturated aqueous Na bicarbonate solution, the organic phase dried, vacuum concentrated and the residue with diisopropyl ether Brought crystallization. 2 g of product were obtained, mp. 93-95 ° C.

e) Die Titelverbindung wurde erhalten, indem 0,6 g (2,24 mmol) der vorstehenden Ethylesters mit 120 mg Lithiumhydroxid in 60 ml Methanol/Wasser (3 : 1) bei 20°C verseift wurden. Nachdem i.Vak. eingeengt wurde, säuerte man an, extrahierte den Rückstand bei 20°C mit Tetrahydrofuran, engte das Filtrat i.Vak. ein und brachte den gelben, harzigen Rückstand mit Diethylether zur Kristallisation. Man erhielt 0,14 g der Titelverbindung, Fp. 130°C (Zersetzung), die stark hygroskopisch ist. Der Rückstand des eingedampften Reaktionsgemisches wurde dann dreimal mit je 50 ml heißen Aceton extrahiert und der Eindampfrückstand mit Diethylether zur Kristallisation gebracht. Man erhielt weitere 0,35 g der Titelverbindung, Fp. 155°C (Zersetzung).e) The title compound was obtained by adding 0.6 g (2.24 mmol) of the above ethyl ester with 120 mg of lithium hydroxide in 60 ml Methanol / water (3: 1) were saponified at 20 ° C. After i.Vak. constricted was acidified, the residue was extracted at 20 ° C. Tetrahydrofuran, the filtrate i.Vak. and brought the yellow, resinous Residue with diethyl ether for crystallization. 0.14 g of was obtained Title compound, mp 130 ° C (decomposition), which is highly hygroscopic. The residue of the evaporated reaction mixture was then three times with 50 ml of hot acetone each and the evaporation residue with diethyl ether  brought to crystallization. A further 0.35 g of the title compound was obtained, Mp 155 ° C (decomposed).

Beispiel 18Example 18

3,5-Diethoxypyridin-2-carbonsäure-glycylamid3,5-diethoxypyridine-2-carboxylic acid glycylamide

Beispiel 19Example 19

3-Methoxy-6-(3-methylbutyloxy)pyridin-2-carbonsäure-glycylamid Fp.: 105-107°C (aus wäßriger Salzsäure, pH 3-4)3-methoxy-6- (3-methylbutyloxy) pyridine-2-carboxylic acid glycylamide Mp .: 105-107 ° C (from aqueous hydrochloric acid, pH 3-4)

Beispiel 20Example 20

3-Benzyloxy-4-(3-ethyloxypropyloxy)pyridin-2-carbonsäure-glycylamid Fp. 118-120°C (aus Aceton)
Laut ¹H-NMR enthält das Produkt ca. 15% des 3-Hydroxy-Derivates.3-benzyloxy-4- (3-ethyloxypropyloxy) pyridine-2-carboxylic acid glycylamide mp 118-120 ° C (from acetone)
According to 1 H-NMR, the product contains approximately 15% of the 3-hydroxy derivative.

Beispiel 21Example 21

3-Benzyloxy-4-hexyloxypyridin-2-carbonsäure-glycylamid Fp. 130-132°C (aus wäßriger Salzsäure)3-benzyloxy-4-hexyloxypyridine-2-carboxylic acid glycylamide Mp 130-132 ° C (from aqueous hydrochloric acid)

Beispiel 22Example 22

6-(2-Butoxyethyloxy)-3-methoxypyridin-2-carbonsäure-glycylamid6- (2-butoxyethyloxy) -3-methoxypyridine-2-carboxylic acid glycylamide

Beispiel 23Example 23

6-Butyloxy-3-methoxypyridin-2-carbonsäure-glycylamid6-butyloxy-3-methoxypyridine-2-carboxylic acid glycylamide

Beispiel 24Example 24

3-Ethyloxy-6-methylpyridin-2-carbonsäure-glycylamid3-ethyloxy-6-methylpyridine-2-carboxylic acid glycylamide

Beispiel 25Example 25

6-Benzyloxy-3-methoxypyridin-2-carbonsäure-glycylamid 6-benzyloxy-3-methoxypyridine-2-carboxylic acid glycylamide  

Beispiel 26Example 26

3-Benzyloxypyridin-2-carbonsäure-glycylamid3-benzyloxypyridine-2-carboxylic acid glycylamide

Beispiel 27Example 27

3-Methoxypyridin-2-carbonsäure-glycylamid amorphe Substanz, hergestellt durch Verseifung des 3-Methoxypyridin-2- carbonsäure-(glycylethylester)amids, Fp. 141-142°C (unter Gasentwicklung, aus Diethylether).3-methoxypyridine-2-carboxylic acid glycylamide amorphous substance produced by saponification of 3-methoxypyridine-2- carboxylic acid (glycylethyl ester) amides, mp. 141-142 ° C (with gas evolution, from diethyl ether).

Dieser Ethylester wurde durch katalytische Hydrierung von 4-Chlor-3- methoxypyridin-2-carbonsäure-(glycylethylester)amid (siehe Beispiel 2c) erhalten, welches aus 4-Chlor-3-methoxypyridin-2-carbonsäure (Fp. 119-120°C, aus 4-Chlor-3-methoxy-2-methylpyridin-N-oxid durch Reaktion mit Acetanhydrid/Eisessig und nachfolgender Oxidation des 2-Hydroxymethylpyridin- Derivates) (siehe Beispiel 2a, b) und Glycinethylester-Hydrochlorid erhalten wurde.This ethyl ester was obtained by catalytic hydrogenation of 4-chloro-3- methoxypyridine-2-carboxylic acid (glycylethyl ester) amide (see Example 2c) obtained, which from 4-chloro-3-methoxypyridine-2-carboxylic acid (mp. 119-120 ° C, from 4-chloro-3-methoxy-2-methylpyridine-N-oxide by reaction with Acetic anhydride / glacial acetic acid and subsequent oxidation of the 2-hydroxymethylpyridine Derivates) (see Example 2a, b) and glycine ethyl ester hydrochloride has been.

Beispiel 28Example 28

3-Ethoxypyridin-2-carbonsäure-glycylamid3-ethoxypyridine-2-carboxylic acid glycylamide

Beispiel 29Example 29

3-Propyloxypyridin-2-carbonsäure-glycylamid3-propyloxypyridine-2-carboxylic acid glycylamide

Beispiel 30Example 30

3-Butyloxypyridin-2-carbonsäure-glycylamid3-butyloxypyridine-2-carboxylic acid glycylamide

a) 3-n-Butyloxypyridin-2-carbonsäurea) 3-n-Butyloxypyridine-2-carboxylic acid

9,8 g (70 mmol) 3-Hydroxypyridin-2-carbonsäure wurden in 150 ml N,N-Dimethylacetamid bei 20°C unter Rühren portionsweise mit 6 g (150 mmol) NaH (60%, in Mineralöl) versetzt. Nach 30 min. tropfte man 15 ml (140 mmol) Butylbromid zu und erwärmte 2,5 h zwischen 95°C und 125°C. 9.8 g (70 mmol) of 3-hydroxypyridine-2-carboxylic acid were dissolved in 150 ml N, N-dimethylacetamide at 20 ° C. with stirring in portions with 6 g (150 mmol) NaH (60%, in mineral oil) added. After 30 min. 15 ml was dropped (140 mmol) butyl bromide and heated between 95 ° C and 125 ° C for 2.5 h.  

Nach dem Abkühlen wurde i. Vak. eingeengt, mit wäßriger Na-Bicarbonat- Lösung behandelt, mit Dichlormethan extrahiert, nach dem Trocknen der Rückstand chromatographisch mit Ethylacetat an Kieselgel gereinigt. Die so erhaltenen 13 g öliges Produkt wurden in 250 ml 1,5 N methanolische Natronlauge eingetragen, 30 min bei 20°C gerührt, i. Vak. eingeengt, in 200 ml Wasser aufgenommen, mit Dichlormethan extrahiert, die wäßrige Phase mit conc. wäßriger Salzsäure auf pH 1 gebracht, i. Vak. eingeengt, der Rückstand mit Ethylacetat, sodann mit wasserfreiem Ethanol behandelt. Die erhaltenen Lösungen wurden eingeengt und der Rückstand mit Aceton zur Kristallisation gebracht. Man erhielt 9,3 g Produkt (Fp. 93-95°C), das laut ¹H-NMR noch ca. 20% 3-Hydroxypyridin-2-carbonsäure enthielt.After cooling, i. Vac. concentrated, with aqueous Na bicarbonate Treated solution, extracted with dichloromethane, after drying the The residue was purified by chromatography on silica gel using ethyl acetate. The 13 g of oily product thus obtained were in 250 ml of 1.5 N methanolic Sodium hydroxide solution added, stirred at 20 ° C. for 30 min, i. Vac. concentrated in 200 ml Water taken up, extracted with dichloromethane, the aqueous phase with conc. brought aqueous hydrochloric acid to pH 1, i. Vac. concentrated, the residue treated with ethyl acetate, then with anhydrous ethanol. The received Solutions were concentrated and the residue was crystallized with acetone brought. 9.3 g of product (mp. 93-95 ° C.) were obtained, which according to 1 H-NMR was still approx. Contained 20% 3-hydroxypyridine-2-carboxylic acid.

b) 4 g (20 mmol) des obigen Produkts wurden in 200 ml wasserfreiem Tetrahydrofuran und 100 ml wasserfreiem Acetonitril bei 20°C unter Rühren mit 2,8 g (20 mmol) Glycinethylester-Hydrochlorid, 5,2 ml (40 mmol) N-Ethylmorpholin, 2,7 g (20 mmol) 1-Hydroxy-1H-benztriazol und 3,0 ml (20 mmol) N,N′-Diisopropylcarbodiimid versetzt und 20 h bei 20°C gerührt. Nach Aufarbeitung (Behandlung mit Na-Bicarbonat-Lösung, Abtrennung von ausgefallenem Diisopropylharnstoff wurde nach Chromatographie an Kieselgel (Ethylacetat/n-Heptan 1 : 1; dann reines Ethylacetat) 3,5 g öliges Produkt erhalten, das noch N,N′-Diisopropylharnstoff enthielt.b) 4 g (20 mmol) of the above product were anhydrous in 200 ml Tetrahydrofuran and 100 ml of anhydrous acetonitrile at 20 ° C with stirring with 2.8 g (20 mmol) glycine ethyl ester hydrochloride, 5.2 ml (40 mmol) N-ethylmorpholine, 2.7 g (20 mmol) of 1-hydroxy-1H-benzotriazole and 3.0 ml (20 mmol) N, N'-diisopropylcarbodiimide were added and the mixture was stirred at 20 ° C. for 20 h. After working up (treatment with Na bicarbonate solution, separation of precipitated diisopropylurea was after chromatography on silica gel (Ethyl acetate / n-heptane 1: 1; then pure ethyl acetate) 3.5 g of oily product obtained, which still contained N, N'-diisopropylurea.

Dieses Gemisch wurde bei 20°C unter Rühren in 150 ml 1,5 N methanolische Natronlauge eingetragen und 30 min gerührt.This mixture was at 20 ° C with stirring in 150 ml of 1.5 N methanolic Sodium hydroxide solution added and stirred for 30 min.

Dann wurde i. Vak. eingeengt, der Rückstand in Wasser aufgenommen mit 200 ml Dichlormethan extrahiert, die wäßrige Phase mit conc. wäßriger HCl auf pH 1 gebracht, i. Vak. eingeengt, der Rückstand mit wasserfreiem Ethanol, sodann mit N,N-Dimethylformamid behandelt, jeweils vom Ungelösten abfiltriert, eingeengt und der jeweilige Rückstand mit Ethylacetat zur Kristallisation gebracht. Man erhielt 1,65 g der Titelverbindung aus der Ethanol-Phase (laut ¹H-NMR leicht verunreinigt, Fp. 170°C unter Gasentwicklung) und weitere 0,63 g aus der Dimethylformamid-Phase (Fp. 182°C, unter Gasentwicklung). Then i. Vac. concentrated, the residue taken up in water with Extracted 200 ml dichloromethane, the aqueous phase with conc. aqueous HCl brought pH 1, i. Vac. concentrated, the residue with anhydrous ethanol, then treated with N, N-dimethylformamide, each filtered off from the undissolved, concentrated and the respective residue with ethyl acetate for crystallization brought. 1.65 g of the title compound were obtained from the ethanol phase (according to 1 H-NMR slightly contaminated, mp. 170 ° C with gas evolution) and others 0.63 g from the dimethylformamide phase (mp. 182 ° C, with gas evolution).  

Beispiel 31Example 31

3-(4-Chlorbenzyloxy)pyridin-2-carbonsäure-glycylamid3- (4-chlorobenzyloxy) pyridine-2-carboxylic acid glycylamide

a) 3-(4-Chlorbenzyloxy)pyridin-2-carbonsäure-(4-chlorbenzyl)estera) 3- (4-Chlorobenzyloxy) pyridine-2-carboxylic acid (4-chlorobenzyl) ester

8,4 g (60 mmol) 3-Hydroxypyridin-2-carbonsäure wurden analog Beispiel 30a) in N,N-Dimethylacetamid mit 5,2 g (ca. 130 mmol, 60%) Natriumhydrid und 19,3 g (120 mmol) 4-Chlorbenzylchlorid alkyliert (3 h, 110°C). Nach Einengen i.Vak., Extrahieren mit Na-bicarbonat-Lösung wurde der Rückstand mit Heptan/Ethylacetat (1 : 1) an Kieselgel gereinigt und aus entsprechenden Fraktionen 14,8 g des Produkts mit Diisopropylether zur Kristallisation gebracht, Fp. 92-94°C.8.4 g (60 mmol) of 3-hydroxypyridine-2-carboxylic acid were analogous to Example 30a) N, N-dimethylacetamide with 5.2 g (approx. 130 mmol, 60%) sodium hydride and 19.3 g (120 mmol) 4-chlorobenzyl chloride alkylated (3 h, 110 ° C). After constriction i.Vak., extraction with Na bicarbonate solution, the residue was with Heptane / ethyl acetate (1: 1) purified on silica gel and from appropriate Fractions 14.8 g of the product crystallized with diisopropyl ether, Mp 92-94 ° C.

b) 3-(4-Chlorbenzyloxy)pyridin-2-carbonsäureb) 3- (4-chlorobenzyloxy) pyridine-2-carboxylic acid

9,7 g (25 mmol) des vorstehenden Esters wurden mit 200 ml 1,5 N methanolischer Natronlauge verseift (24 h, 20°C). Nach Aufarbeitung (Einengen, Aufnahme des Rückstands in Wasser, Extrahieren mit Dichlormethan und Ansäuern) wurden 6,5 g Produkt erhalten, Fp. 144°C (aus Wasser, Zersetzung<9.7 g (25 mmol) of the above ester were treated with 200 ml of 1.5 N Saponified methanolic sodium hydroxide solution (24 h, 20 ° C). After refurbishment (Concentrate, take up the residue in water, extract with dichloromethane and acidifying) 6.5 g of product were obtained, mp. 144 ° C. (from water, Decomposition <

c) 3-(4-Chlorbenzyloxy)pyridin-2-carbonsäure-(glycylethylester)amidc) 3- (4-chlorobenzyloxy) pyridine-2-carboxylic acid (glycylethyl ester) amide

3,2 g (12 mmol) der vorstehenden Pyridin-2-carbonsäure wurden analog Beispiel 17 d) mit 1,7 g (12 mmol) Glycinethylester-Hydrochlorid, 1,62 (12 mmol) 1-Hydroxy-(1H)-benztriazol, 3,3 ml (25 mmol) N-Ethylmorpholin und 5,2 g (12 mmol) N-Cyclohexyl-N′-(2-morpholinoethyl)-carbodiimid-methyl-p- toluolsulfonat) umgesetzt. Nach Aufarbeitung wurden 3,0 g des Produkts mit Diisopropylether zur Kristallisation gebracht, Fp. 106-108°C.3.2 g (12 mmol) of the above pyridine-2-carboxylic acid were analogous to Example 17 d) with 1.7 g (12 mmol) glycine ethyl ester hydrochloride, 1.62 (12 mmol) 1-hydroxy- (1H) -benztriazole, 3.3 ml (25 mmol) of N-ethylmorpholine and 5.2 g (12 mmol) N-cyclohexyl-N ′ - (2-morpholinoethyl) carbodiimide-methyl-p- toluenesulfonate) implemented. After working up, 3.0 g of the product were Diisopropyl ether brought to crystallization, mp. 106-108 ° C.

d) Die Titelverbindung wurde durch Verseifen des vorstehenden Ethylesters erhalten. 0,9 g (2,5 mmol) des Ethylesters wurden in 60 ml Methanol/Wasser (3 : 1) mit 120 mg (5 mmol) Lithiumhydroxid versetzt und 1 h bei 20°C gerührt. Dann wurde i. Vak. eingeengt, die erhaltene wäßrige Phase auf pH 3 gebracht, die entstandene Fällung abgesaugt, mit Wasser gewaschen und i. Vak. getrocknet. Man erhielt 0,52 g der Titelverbindung, Fp. 155-157°C.d) The title compound was prepared by saponifying the above ethyl ester receive. 0.9 g (2.5 mmol) of the ethyl ester were in 60 ml of methanol / water  (3: 1) with 120 mg (5 mmol) of lithium hydroxide and stirred at 20 ° C for 1 h. Then i. Vac. concentrated, the aqueous phase obtained brought to pH 3, the precipitate formed is suction filtered, washed with water and i. Vac. dried. 0.52 g of the title compound, mp 155-157 ° C., was obtained.

Beispiel 32Example 32

3-(3-Methoxybenzyloxy)pyridin-2-carbonsäure-glycylamid3- (3-methoxybenzyloxy) pyridine-2-carboxylic acid glycylamide

a) 3-(3-Methoxybenzyloxy)pyridin-2-carbonsäure-(3-methoxybenzyl)estera) 3- (3-Methoxybenzyloxy) pyridine-2-carboxylic acid (3-methoxybenzyl) ester

Analog Beispiel 38a) wurden aus 8,4 g (60 mmol) 3-Hydroxypyridin-2- carbonsäure und 3-Methoxybenzylchlorid nach Chromatographie an Kieselgel 10 g des Produkts als farbloses Öl erhalten, die weiter umgesetzt wurden.Analogously to Example 38a), 8.4 g (60 mmol) of 3-hydroxypyridine-2- carboxylic acid and 3-methoxybenzyl chloride after chromatography on silica gel Obtained 10 g of the product as a colorless oil, which were further reacted.

b) 3-(3-Methoxybenzyloxy)pyridin-2-carbonsäureb) 3- (3-methoxybenzyloxy) pyridine-2-carboxylic acid

10 g des vorstehenden Esters wurden in 300 ml 1,5 N methanolischer Natronlauge verseift. Man erhielt 7,5 g Produkt, Fp. 147°C (Zersetzung, aus wäßriger Salzsäure<)10 g of the above ester were more methanolic in 300 ml of 1.5 N Saponified sodium hydroxide solution. 7.5 g of product, mp. 147 ° C. (decomposition) were obtained aqueous hydrochloric acid <)

c) 3-(3-Methoxybenzyloxy)pyridin-2-carbonsäure-(glycylethylester)amidc) 3- (3-methoxybenzyloxy) pyridine-2-carboxylic acid (glycylethyl ester) amide

3,2 g (12 mmol) der vorstehenden Carbonsäure wurden analog Beispiel 31c) umgesetzt. Man isolierte 3,6 g öliges Rohprodukt, das laut ¹H-NMR-Spektrum noch N-Ethylmorpholin enthielt. Hieraus wurde die reine Substanz erhalten, Fp. 135-137°C (aus Diisopropylether/Ethylacetat).3.2 g (12 mmol) of the above carboxylic acid were analogous to Example 31c) implemented. 3.6 g of oily crude product were isolated, according to the 1 H-NMR spectrum still contained N-ethylmorpholine. The pure substance was obtained from this, mp. 135-137 ° C (from diisopropyl ether / ethyl acetate).

d) 2,1 g (6 mmol) des vorstehenden Produkts wurden mit 0,4 g NaOH in 60 ml Methanol verseift. Man erhielt nach Ansäuern auf pH 31, 6 g der Titelverbindung als farblos kristalline Substanz, Fp. 89-91°C (aus wäßriger Salzsäure). d) 2.1 g (6 mmol) of the above product were mixed with 0.4 g NaOH in 60 ml Methanol saponified. After acidification to pH 31.6 g of Title compound as a colorless crystalline substance, mp. 89-91 ° C (from aqueous Hydrochloric acid).  

Beispiel 33Example 33

3-(2-Phenylethyloxy)pyridin-2-carbonsäure-glycylamid-Natriumsalz3- (2-phenylethyloxy) pyridine-2-carboxylic acid glycylamide sodium salt

a) 3-((2-Phenylethyloxy)pyridin-2-carbonsäurea) 3 - ((2-Phenylethyloxy) pyridine-2-carboxylic acid

Analog Beispiel 30 a) wurden 8,4 g (60 mmol) 3-Hydroxypyridin-2-carbonsäure mit NaH/2-Phenylethylbromidin N,N-Dimethylacetatamid alkyliert. Die nach säulenchromatographischer Reinigung erhaltenen 10 g öliges Produkts wurden analog Beispiel 30a) mit methanolischer Natronlauge verseift. Man erhielt 3 g Produkt (Fp. 145°C (unter Schäumen, aus Aceton), das laut ¹H-NMR-Spektrum ca. 25% 3-Hydroxypicolinsäure enthält.Analogously to Example 30 a), 8.4 g (60 mmol) of 3-hydroxypyridine-2-carboxylic acid alkylated with NaH / 2-phenylethylbromidine N, N-dimethylacetamide. The after 10 g of oily product obtained by column chromatography were obtained analogous to example 30a) with methanolic sodium hydroxide solution. 3 g were obtained Product (mp. 145 ° C (under foaming, from acetone), according to the 1 H-NMR spectrum contains about 25% 3-hydroxypicolinic acid.

b) 3-((2-Phenylethyl)oxy)pyridin-2-carbonsäure-(glycylethylester)amidb) 3 - ((2-Phenylethyl) oxy) pyridine-2-carboxylic acid (glycylethyl ester) amide

Analog Beispiel 30b) wurden 2,9 g der vorstehenden Verbindung mit Glycinethylester-Hydrochlorid, N-Ethylmorpholin, 1-Hydroxy-1H-benztriazol und N,N-Dicyclohexylcarbodiimid umgesetzt. Nach Aufarbeitung wurde das Rohprodukt mit Ethylacetat an Kieselgel chromatographiert. Als Nebenprodukt wurden zunächst 3-Hydroxy-pyridin-2-carbonsäure-(glycylethylester)amid eluiert und aus entsprechenden Fraktionen mit Petrolether zur Kristallisation gebracht, 1,1 g (Fp. 86-88°C, starke Fluoreszenz im UV-Licht). Dann wurde aus entsprechenden Fraktionen das Produkt mit Diisopropylether zur Kristallisation gebracht und 1,7 g des Produkts Fp. 73-75°C erhalten.Analogously to Example 30b), 2.9 g of the above compound were mixed with Glycine ethyl ester hydrochloride, N-ethylmorpholine, 1-hydroxy-1H-benzotriazole and N, N-dicyclohexylcarbodiimide implemented. After working it up Chromatograph crude product with ethyl acetate on silica gel. As a by-product 3-hydroxy-pyridine-2-carboxylic acid (glycylethyl ester) amide were first eluted and crystallized from corresponding fractions with petroleum ether, 1.1 g (mp. 86-88 ° C, strong fluorescence in UV light). Then was out corresponding fractions the product with diisopropyl ether for crystallization brought and 1.7 g of the product mp. 73-75 ° C obtained.

c) Die Titelverbindung wurde erhalten, indem 0,99 g (3 mmol) des vorstehenden Ethylesters mit 100 ml 1 N methanoIischer Natronlauge verseift wurden. Nachdem 1 h bei 20°C gerührt wurde, löste man nach dem Einengen den Rückstand in wenig Wasser, extrahierte mit Dichlormethan, säuerte die wäßrige Phase unter Eiskühlung mit conc. wäßriger Salzsäure auf pH 1 an, engte i. Vak. ein, extrahierte den Rückstand zweimal mit Tetrahydrofuran, engte ein, löste den Rückstand in wenig Wasser/Tetrahydrofuran (1 : 1), versetzte mit 252 mg (3 mmol) Natriumbicarbonat. Man engte zur Trockne ein und brachte den Rückstand mit wasserfreiem Ethanol zur Kristallisation. 0,38 g der Titelverbindung wurden als Natriumsalz erhalten, Fp. ) 300°C.c) The title compound was obtained by adding 0.99 g (3 mmol) of the above Ethyl esters were saponified with 100 ml of 1 N methanolic sodium hydroxide solution. After the mixture had been stirred at 20 ° C. for 1 h, the was dissolved after the concentration Residue in a little water, extracted with dichloromethane, acidified the aqueous Phase under ice cooling with conc. aqueous hydrochloric acid to pH 1, i. Vac. , extracted the residue twice with tetrahydrofuran, concentrated, dissolved the residue in a little water / tetrahydrofuran (1: 1), treated with 252 mg (3 mmol) sodium bicarbonate. One constricted to dryness and brought it  Residue with anhydrous ethanol for crystallization. 0.38 g of The title compound was obtained as the sodium salt, mp 300 ° C.

Beispiel 34Example 34

3-(4-Trifluormethylbenzyloxy)pyridin-2-carbonsäure-glycylamid3- (4-trifluoromethylbenzyloxy) pyridine-2-carboxylic acid glycylamide

Beispiel 35Example 35

3-(4-(2-Propyl)benzyloxy)pyridin-2-carbonsäure-glycylamid3- (4- (2-Propyl) benzyloxy) pyridine-2-carboxylic acid glycylamide

Beispiel 36Example 36

3-(3-Fluorbenzyloxy)pyridin-2-carbonsäure-glycylamid3- (3-fluorobenzyloxy) pyridine-2-carboxylic acid glycylamide

Beispiel 37Example 37

3-(4-Fluorbenzyloxy)pyridin-2-carbonsäure-glycylamid Fp.: 135-138°C (aus wäßriger Salzsäure pH 3-4)3- (4-fluorobenzyloxy) pyridine-2-carboxylic acid glycylamide Mp .: 135-138 ° C (from aqueous hydrochloric acid pH 3-4)

Beispiel 38Example 38

3-(2,4-Dichlorbenzyloxy)pyridin-2-carbonsäure-glycylamid3- (2,4-dichlorobenzyloxy) pyridine-2-carboxylic acid glycylamide

Beispiel 39Example 39

3-(4-(2,2,2-Trifluorethyloxy)benzyloxy)pyridin-2-carbonsäure-glycyla-mid3- (4- (2,2,2-trifluoroethyloxy) benzyloxy) pyridine-2-carboxylic acid glycyla-mid

Beispiel 40Example 40

3-(3-Chlorbenzyloxy)pyridin-2-carbonsäure-glycylamid3- (3-chlorobenzyloxy) pyridine-2-carboxylic acid glycylamide

Beispiel 41Example 41

3-(3,4-Dichlorbenzyloxy)pyridin-2-carbonsäure-glycylamid3- (3,4-dichlorobenzyloxy) pyridine-2-carboxylic acid glycylamide

Beispiel 42Example 42

3-(3-Trifluormethylbenzyloxy)pyridin-2-carbonsäure-glycylamid 3- (3-trifluoromethylbenzyloxy) pyridine-2-carboxylic acid glycylamide  

Beispiel 43Example 43

3-(4-Trifluormethoxybenzyloxy)pyridin-2-carbonsäure-glycylamid3- (4-trifluoromethoxybenzyloxy) pyridine-2-carboxylic acid glycylamide

Die folgenden Beispiele wurden analog hergestellt:The following examples were prepared analogously:

Beispiel 44Example 44

3-(3-Ethoxybenzyloxy)pyridin-2-carbonsäure-glycylamid3- (3-ethoxybenzyloxy) pyridine-2-carboxylic acid glycylamide

Beispiel 45Example 45

3-(4-Cyanobenzyloxy)pyridin-2-carbonsäure-glycylamid3- (4-cyanobenzyloxy) pyridine-2-carboxylic acid glycylamide

Beispiel 46Example 46

3-((2-Pyridylmethyl)oxy)pyridin-2-carbonsäure-glycylamid-Hydrochlori-d3 - ((2-pyridylmethyl) oxy) pyridine-2-carboxylic acid glycylamide hydrochloride

Beispiel 47Example 47

3-((3-Pyridylmethyl)oxy)pyridin-2-carbonsäure-glycylamid-Hydrochlori-d3 - ((3-pyridylmethyl) oxy) pyridine-2-carboxylic acid glycylamide hydrochloride

Beispiel 48Example 48

3-((4-Pyridylmethyl)oxy)pyridin-2-carbonsäure-glycylamid-Hydrochlori-d3 - ((4-pyridylmethyl) oxy) pyridine-2-carboxylic acid glycylamide hydrochloride

Beispiel 49Example 49

3-(2-Thienylmethyl)oxy)pyridin-2-carbonsäure-glycylamid3- (2-thienylmethyl) oxy) pyridine-2-carboxylic acid glycylamide

Beispiel 50Example 50

3-(3,5-Dimethoxybenzyloxy)pyridin-2-carbonsäure-glycylamid3- (3,5-Dimethoxybenzyloxy) pyridine-2-carboxylic acid glycylamide

Beispiel 51Example 51

3-Cyclohexyloxypyridin-2-carbonsäure-glycylamid3-cyclohexyloxypyridine-2-carboxylic acid glycylamide

Beispiel 52Example 52

3-(3-Phenylpropyloxy)pyridin-2-carbonsäure-glycylamid 3- (3-phenylpropyloxy) pyridine-2-carboxylic acid glycylamide  

Beispiel 53Example 53

3-(4-Phenylbutyloxy)pyridin-2-carbonsäure-glycylamid3- (4-phenylbutyloxy) pyridine-2-carboxylic acid glycylamide

Beispiel 54Example 54

3-(((4-Methoxy-2-pyridyl)methyl)oxy)pyridin-2-carbonsäure-glycylamid-3 - (((4-methoxy-2-pyridyl) methyl) oxy) pyridine-2-carboxylic acid glycylamide-

Beispiel 55Example 55

3-(((4-Ethoxy-2-pyridyl)methyl)oxy)pyridin-2-carbonsäure-glycylamid3 - (((4-Ethoxy-2-pyridyl) methyl) oxy) pyridine-2-carboxylic acid glycylamide

Beispiel 56Example 56

3-Methylthiopyridin-2-carbonsäure-glycylamid3-methylthiopyridine-2-carboxylic acid glycylamide

Beispiel 57Example 57

3-Benzylthiopyridin-2-carbonsäure-glycylamid3-benzylthiopyridine-2-carboxylic acid glycylamide

Beispiel 58Example 58

3-(3-Chlorphenoxy)pyridin-2-carbonsäure-glycylamid3- (3-chlorophenoxy) pyridine-2-carboxylic acid glycylamide

Beispiel 59Example 59

3-(3-Methoxyphenoxy)pyridin-2-carbonsäure-glycylamid3- (3-methoxyphenoxy) pyridine-2-carboxylic acid glycylamide

Beispiel 60Example 60

3-Phenoxypyridin-2-carbonsäure-glycylamid3-phenoxypyridine-2-carboxylic acid glycylamide

Beispiel 61Example 61

3-Butyloxypyridin-2-carbonsäure-L-alanylamid3-butyloxypyridine-2-carboxylic acid L-alanylamide

Beispiel 62Example 62

3-Butyloxypyridin-2-carbonsäure-D-alanylamid3-butyloxypyridine-2-carboxylic acid D-alanylamide

Beispiel 63Example 63

3-Benzyloxypyridin-2-carbonsäure-β-alanylamid 3-benzyloxypyridine-2-carboxylic acid-β-alanylamide  

Beispiel 64Example 64

3-(3-Methylbutyloxy)pyridin-2-carbonsäure-L-leucylamid3- (3-methylbutyloxy) pyridine-2-carboxylic acid L-leucylamide

Beispiel 65Example 65

4-Methoxyisochinolin-3-carbonsäure-glycylamid4-methoxyisoquinoline-3-carboxylic acid glycylamide

Beispiel 66Example 66

4-Ethoxyisochinolin-3-carbonsäure-glycylamid4-ethoxyisoquinoline-3-carboxylic acid glycylamide

Beispiel 67Example 67

4-Propyloxychinolin-3-carbonsäure-glycylamid4-propyloxyquinoline-3-carboxylic acid glycylamide

Beispiel 68Example 68

4-(3-Methylbutyloxy)isochinolin-3-carbonsäure-glycylamid4- (3-methylbutyloxy) isoquinoline-3-carboxylic acid glycylamide

Beispiel 69Example 69

4-Methoxy-5,6,7,8-tetrahydroisochinolin-3-carbonsäure-glycylamid4-methoxy-5,6,7,8-tetrahydroisoquinoline-3-carboxylic acid glycylamide

Beispiel 70Example 70

4-(3-Methylbutyloxy)-5,6,7,8-tetrahydroisochinolin-3-carbonsäure-gly-cylamid4- (3-methylbutyloxy) -5,6,7,8-tetrahydroisoquinoline-3-carboxylic acid glycylamide

Beispiel 71Example 71

4-Ethoxy-5,6,7,8-tetrahydroisochinolin-3-carbonsäure-glycylamid4-ethoxy-5,6,7,8-tetrahydroisoquinoline-3-carboxylic acid glycylamide

Beispiel 72Example 72

4-Benzyloxy-5,6,7,8-tetrahydroisochinolin-3-carbonsäure-glycylamid4-Benzyloxy-5,6,7,8-tetrahydroisoquinoline-3-carboxylic acid glycylamide

Beispiel 73Example 73

4-Benzyloxyisochinolin-3-carbonsäure-glycylamid4-benzyloxyisoquinoline-3-carboxylic acid glycylamide

Beispiel 74Example 74

4-(3-Methoxybenzyloxy)-5,6,7,8-tetrahydroisochinolin-3-carbonsäure-g-lycylamid 4- (3-methoxybenzyloxy) -5,6,7,8-tetrahydroisoquinoline-3-carboxylic acid g-lycylamide  

Beispiel 75Example 75

7-Brom-4-methoxyisochinolin-3-carbonsäure-glycylamid7-bromo-4-methoxyisoquinoline-3-carboxylic acid glycylamide

Beispiel 76Example 76

7-Methoxy-4-methoxyisochinolin-3-carbonsäure-glycylamid7-methoxy-4-methoxyisoquinoline-3-carboxylic acid glycylamide

Beispiel 77Example 77

3-Methoxy-6-((3-methylbutyloxy)methyl)pyridin-2-carbonsäure-glycylam-id3-methoxy-6 - ((3-methylbutyloxy) methyl) pyridine-2-carboxylic acid glycylam id

Beispiel 78Example 78

3-Methoxy-6-((cyclohexyloxy)methyl)pyridin-2-carbonsäure-glycylamid3-methoxy-6 - ((cyclohexyloxy) methyl) pyridine-2-carboxylic acid glycylamide

Beispiel 79Example 79

3-Methoxy-6-benzyloxymethylpyridin-2-carbonsäure-glycylamid3-methoxy-6-benzyloxymethylpyridine-2-carboxylic acid glycylamide

Beispiel 80Example 80

5-Carboxy-3-methoxypyridin-2-carbonsäure-glycylamid5-carboxy-3-methoxypyridine-2-carboxylic acid glycylamide

Beispiel 81Example 81

5-Ethoxycarbonyl-3-methoxypyridin-2-carbonsäure-glycylamid5-ethoxycarbonyl-3-methoxypyridine-2-carboxylic acid glycylamide

Beispiel 82Example 82

5-(3-Pentyloxy)carbonyl-3-methoxypyridin-2-carbonsäure-glycylamid5- (3-pentyloxy) carbonyl-3-methoxypyridine-2-carboxylic acid glycylamide

Beispiel 83Example 83

5-Cyclohexyloxycarbonyl-3-methoxypyridin-2-carbonsäure-glycylamid5-cyclohexyloxycarbonyl-3-methoxypyridine-2-carboxylic acid glycylamide

Beispiel 84Example 84

5-(n-Butylaminocarbonyl)-3-methoxypyridin-2-carbonsäure-glycylamid5- (n-butylaminocarbonyl) -3-methoxypyridine-2-carboxylic acid glycylamide

Beispiel 85Example 85

5-(2-Methyl-2-butylaminocarbonyl)-3-methoxypyridin-2-carbonsäure-gly-cylamid 5- (2-methyl-2-butylaminocarbonyl) -3-methoxypyridine-2-carboxylic acid glycylamide  

Beispiel 86Example 86

5-(Cyclohexylaminocarbonyl)-3-methoxypyridin-2-carbonsäure-glycylami-d5- (Cyclohexylaminocarbonyl) -3-methoxypyridine-2-carboxylic acid glycylami-d

Beispiel 87Example 87

5-(Cyclohexylaminocarbonyl)-3-ethyloxypyridin-2-carbonsäure-glycylam-id5- (Cyclohexylaminocarbonyl) -3-ethyloxypyridine-2-carboxylic acid glycylam-id

Beispiel 88Example 88

5-((2-Phenylethyl)aminocarbonyl)-3-methoxypyridin-2-carbonsäure-glyc-ylamid5 - ((2-phenylethyl) aminocarbonyl) -3-methoxypyridine-2-carboxylic acid glycyllamide

Beispiel 89Example 89

5-((2-(4-Methoxyphenyl)ethyl)aminocarbonyl)-3-methoxypyridin-2-carbo-nsäure- glycylamid5 - ((2- (4-methoxyphenyl) ethyl) aminocarbonyl) -3-methoxypyridine-2-carbonic acid - glycylamide

Beispiel 90Example 90

5-((2-(4-Fluorphenyl)ethyl)aminocarbonyl)-3-methoxypyridin-2-carbons-äure- glycylamid5 - ((2- (4-fluorophenyl) ethyl) aminocarbonyl) -3-methoxypyridine-2-carboxylic acid - glycylamide

Beispiel 91Example 91

5-((2-(4-Methoxyphenyl)ethyl)aminocarbonyl)-3-ethyloxypyridin-2-carb-onsäure- glycylamid5 - ((2- (4-methoxyphenyl) ethyl) aminocarbonyl) -3-ethyloxypyridine-2-carboxylic acid - glycylamide

Beispiel 92Example 92

5-Chlor-3-ethyloxypyridin-2-carbonsäure-glycylamid5-chloro-3-ethyloxypyridine-2-carboxylic acid glycylamide

Beispiel 93Example 93

5-Chlor-3-ethyloxypyridin-2-carbonsäure-glycylamid5-chloro-3-ethyloxypyridine-2-carboxylic acid glycylamide

Beispiel 94Example 94

5-Cyclohexyloxymethyl-3-methoxypyridin-2-carbonsäure-glycylamid5-cyclohexyloxymethyl-3-methoxypyridine-2-carboxylic acid glycylamide

Beispiel 95Example 95

5-(3-Methylbutyl)oxymethyl-3-methoxypyridin-2-carbonsäure-glycylamid- 5- (3-methylbutyl) oxymethyl-3-methoxypyridine-2-carboxylic acid-glycylamide-  

Beispiel 96Example 96

5-Benzyloxymethyl-3-ethyloxypyridin-2-carbonsäure-glycylamid5-benzyloxymethyl-3-ethyloxypyridine-2-carboxylic acid glycylamide

Beispiel 97Example 97

3-((Cyclohexyl)methyloxy)pyridin-2-carbonsäure-glycylamid3 - ((Cyclohexyl) methyloxy) pyridine-2-carboxylic acid glycylamide

Beispiel 98Example 98

3-((2-Cyclohexyl)ethyloxy)pyridin-2-carbonsäure-glycylamid3 - ((2-Cyclohexyl) ethyloxy) pyridine-2-carboxylic acid glycylamide

Beispiel 99Example 99

3-((3-Cyclohexyl)propyloxy)pyridin-2-carbonsäure-glycylamid3 - ((3-Cyclohexyl) propyloxy) pyridine-2-carboxylic acid glycylamide

Beispiel 100Example 100

3-(3-Methylbutyloxy)pyridin-2-carbonsäure-glycylamid3- (3-methylbutyloxy) pyridine-2-carboxylic acid glycylamide

Beispiel 101Example 101

3-Hexyloxypyridin-2-carbonsäure-glycylamid3-hexyloxypyridine-2-carboxylic acid glycylamide

Beispiel 102Example 102

3-(4-Ethylbenzyloxy)pyridin-2-carbonsäure-glycylamid3- (4-ethylbenzyloxy) pyridine-2-carboxylic acid glycylamide

Beispiel 103Example 103

3-(4-Propylbenzyloxy)pyridin-2-carbonsäure-glycylamid3- (4-propylbenzyloxy) pyridine-2-carboxylic acid glycylamide

Beispiel 104Example 104

3-(4-Butylbenzyloxy)pyridin-2-carbonsäure-glycylamid3- (4-butylbenzyloxy) pyridine-2-carboxylic acid glycylamide

Beispiel 105Example 105

3-(4-tert.-Butylbenzyloxy)pyridin-2-carbonsäure-glycylamid3- (4-tert-Butylbenzyloxy) pyridine-2-carboxylic acid glycylamide

Beispiel 106Example 106

6-(3-Methoxybenzyloxy)-3-ethyloxypyridin-2-carbonsäure-glycylamid6- (3-methoxybenzyloxy) -3-ethyloxypyridine-2-carboxylic acid glycylamide

Claims (8)

1. Verbindungen der allgemeinen Formel I in welcher
Q O, S und NR′,
X O und S,
Y C-R³ oder N,
m 0 und 1,
A (C₁-C₄)-Alkylen, das gegebenenfalls substituiert ist mit einem oder zwei Substituenten aus der Reihe Halogen, Cyano, Nitro, Trifluormethyl, (C₁-C₆)-Alkyl, (C₁-C₆)-Hydroxyalkyl, (C₁-C₆)-Alkoxy, -O-[CH₂]x-CfH(2f+1-g)Halg, vorzugsweise (C₁-C₈)-Fluoralkoxy, (C₁-C₈)- Fluoralkenyloxy, (C₁-C₈)-Fluoralkinyloxy, -OCF₂Cl oder -O-CF₂-CHFCl, (C₁-C₆)-Alkylmercapto, (C₁-C₆)-Alkylsulfinyl, (C₁-C₆)-Alkylsulfonyl, (C₁-C₆)-Alkylcarbonyl, (C₁-C₆)-Alkoxycarbonyl, Carbamoyl, N-(C₁-C₄)- Alkylcarbamoyl, N,N-Di-(C₁-C₄)-alkylcarbamoyl, (C₁-C₆)-Alkylcarbonyloxy, (C₃-C₈)-Cycloalkyl, Phenyl, Benzyl, Phenoxy, Benzyloxy, Anilino, N-Methylanilino, Phenylmercapto, Phenylsulfonyl, Phenylsulfinyl, Sulfamoyl, N-(C₁-C₄)-Alkylsulfamoyl, N,N-Di-(C₁-C₄)-alkylsulfamoyl, oder
mit einem substituierten (C₆-C₁₂)-Aryloxy-, (C₇-C₁₁)-Aralkyloxy, (C₆-C₁₂)- Aryl- oder (C₇-C₁₁)-Aralkyl-Rest, der im Arylteil 1, 2, 3, 4 oder 5 gleiche oder verschiedene Substituenten aus der Reihe Halogen, Cyano, Nitro, Trifluormethyl, (C₁-C₆)-Alkyl, (C₁-C₆)-Alkoxy, -O-[CH₂]x-CfH(2f+1-g)Halg, -OCF₂Cl,-O-CF₂-CHFCl, (C₁-C₆)-Alkylmercapto, (C₁-C₆)-Alkylsulfinyl, (C₁- C₆)-Alkylsulfonyl, (C₁-C₆)-Alkylcarbonyl, (C₁-C₆)-Alkoxycarbonyl, Carbamoyl, N-(C₁-C₄)-Alkylcarbamoyl, N,N-Di-(C₁-C₄)-alkylcarbamoyl, (C₁-C₆)-Alkylcarbonyloxy, (C₃-C₈)-Cycloalkyl, Sulfamoyl, N-(C₁-C₄)- Alkylsulfamoyl oder N,N-Di-(C₁-C₄)-alkylsulfamoyl trägt, oder
mit den Substituenten R⁵ des α-C-Atoms einer α-Aminosäure, wobei die natürlichen L-Aminosäuren und ihre D-lsomeren Verwendung finden können;
B eine saure Gruppierung aus der Reihe -CO₂H, -CONHCOR′′′, -CONHSOR′′′, CONHSO₂RW′′′, -NHSO₂CF₃, Tetrazolyl, Imidazolyl oder 3- Hydroxyisoxazolyl bedeutet, wobei R′′′ Aryl, Heteroaryl, (C₃-C₇)- Cycloalkyl oder (C₁-C₄)-Alkyl, gegebenenfalls monosubstituiert mit (C₆- C₁₂)-Aryl, Heteroaryl, OH, SH, (C₁-C₄)-Alkyl, (C₁-C₄)-Alkoxy, (C₁-C₄)- Thioalkyl, -Sulfinyl oder -Sulfonyl, CF₃, Cl, Br, F, I, NO₂, -COOH, (C₂-C₅)- Alkoxycarbonyl, NH₂, Mono- oder Di-(C₁-C₄-alkyl)amino oder (C₁-C₄)- Perfluoroalkyl bedeutet,
R¹, R² und R³ gleich oder verschieden sind und Wasserstoff, Hydroxy, Halogen, Cyano, Trifluormethyl, Nitro, Carboxy, (C₁-C₁₂)-Alkyl, (C₃-C₈)- Cycloalkyl, (C₃-C₈)-Cycloalkyl-(C₁-C₁₂)-alkyl, (C₃-C₈)-Cycloalkoxy, (C₃-C₈)-Cycloalkyl-(C₁-C₁₂)-alkoxy, (C₃-C₈)-Cycloalkyloxy-(C₁-C₁₂)- alkyl, (C₃-C₈)-Cycloalkyloxy-(C₁-C₁₂)-alkoxy, (C₃-C₈)-Cycloalkyl- (C₁-C₈)-alkyl-(C₁-C₆)-alkoxy, (C₃-C₈)-Cycloalkyl-(C₁-C₈)-alkoxy-(C₁- C₆)-alkyl, (C₃-C₈)-Cycloalkyloxy-(C₁-C₈)-alkoxy-(C₁-C₆)-alkyl, (C₃- C₈)-Cycloalkoxy-(C₁-C₈)-alkoxy-(C₁-C₈)-alkoxy, (C₆-C₁₂)-Aryl, (C₇- C₁₆)-Aralkyl, (C₂-C₁₂)-Alkenyl, (C₂-C₁₂)-Alkinyl, (C₁-C₁₂)-Alkoxy, (C₁-C₁₂)-Alkoxy-(C₁-C₁₂)alkyl, (C₁-C₁₂)-Alkoxy-(C₁-C₁₂)alkoxy, (C₁-C₁₂)-Alkoxy-(C₁-C₈)-alkoxy-(C₁-C₈)-alkyl, (C₆-C₁₂)-Aryloxy, (C₇-C₁₆)-Aralkyloxy, (C₆-C₁₂)-Aryloxy-(C₁-C₆)-alkoxy, (C₇-C₁₆)- Aralkoxy-(C₁-C₆)-alkoxy, (C₁-C₈)-Hydroxyalkyl, (C₆-C₁₆)-Aryloxy- (C₁-C₈)-alkyl, (C₇-C₁₆)-Aralkoxy-(C₁-C₈)-alkyl, (C₆-C₁₂)-Aryloxy- (C₁-C₈)-alkoxy-(C₁-C₆)-alkyl, (C₇-C₁₂)-Aralkyloxy-(C₁-C₈)-alkoxy- (C₁-C₆)-alkyl, -O-[CH2-]xCfH(2f+1-g)Fg, -OCF₂Cl, -OCF₂-CHFCl,
(C₁-C₁₂)-Alkylcarbonyl, (C₃-C₈)-Cycloalkylcarbonyl, (C₆-C₁₂)- Arylcarbonyl, (C₇-C₁₆)-Aralkylcarbonyl, Cinnamoyl, (C₂-C₁₂) Alkenylcarbonyl, (C₂-C₁₂)-Alkinylcarbonyl,
(C₁-C₁₂)-Alkoxycarbonyl, (C₁-C₁₂)-Alkoxy-(C₁-C₁₂)-alkoxycarbonyl, (C₆-C₁₂)-Aryloxycarbonyl, (C₇-C₁₆)-Aralkoxycarbonyl, (C₃-C₁₀)- Cycloalkoxycarbonyl, (C₂-C₁₂)-Alkenyloxycarbonyl, (C₂-C₁₂)- Alkinyloxycarbonyl,
(C₁-C₁₂)-Alkylcarbonyloxy, (C₃-C₈)-Cycloalkylcarbonyloxy, (C₆-C₁₂)-Arylcarbonyloxy, (C₇-C₁₆)-Aralkylcarbonyloxy, Cinnamoyloxy, (C₂-C₁₂)-Alkenylcarbonyloxy, (C₂-C₁₂)- Alkinylcarbonyloxy,
(C₁-C₁₂)-Alkoxycarbonyloxy, (C₁-C₁₂)-Alkoxy-(C₁-C₁₂)- alkoxycarbonyloxy, (C₆-C₁₂)-Aryloxycarbonyloxy, (C₇-C₁₆)- Aralkyloxycarbonyloxy, (C₃-C₈)-Cycloalkoxycarbonyloxy, (C₂-C₁₂)- Alkenyloxycarbonyloxy, (C₂-C₁₂)-Alkinyloxycarbonyloxy,
Carbamoyl, N-(C₁-C₁₂)-Alkylcarbamoyl, N,N-Di-(C₁-C₁₂)- alkylcarbamoyl, N-(C₃-C₈)-Cycloalkylcarbamoyl, N,N-Dicyclo (C₃-C₈)-alkylcarbamoyl, N-(C₁-C₁₀)-Alkyl-N-(C₃-C₈)- Cycloalkylcarbamoyl, N-((C₃-C₈)-Cycloalkyl-(C₁-C₆)- alkyl)carbamoyl, N-(C₁-C₆)-Alkyl-N-((C₃-C₈-Cycloalkyl-(C₁-C₆)- alkyl)carbamoyl, N-(+)-Dehydroabietylcarbamoyl, N-(C₁-C₆)-Alkyl- N-Dehydroabietylcarbamoyl, N-(C₆-C₁₂)-Arylcarbamoyl, N-(C₇-C₁₆)- Aralkylcarbamoyl, N-(C₁-C₁₀)-Alkyl-N-(C₆-C₁₆)arylcarbamoyl, N- (C₁-C₁₀)-Alkyl-N-(C₇-C₁₆)-Aralkylcarbamoyl, N-((C₁-C₁₀)-Alkoxy- (C₁-C₁₀)alkyl)carbamoyl, N-((C₆-C₁₆)-Aryloxy (C₁- C₁₀)alkyl)carbamoyl, N-(( C₇-C₁₆)-Aralkylox-(C₁- C₁₀)alkyl)carbamoyl, N-(C₁-C₁₀)-Alkyl-N-((C₁-C₁₀)-Alkoxy-(C₁- C₁₀)alkyl)carbamoyl, N-(C₁-C₁₀)-Alkyl-N-((C₆-C₁₂)-Aryloxy-(C₁- C₁₀)alkyl)carbamoyl, N-(C₁-C₁₀)-Alkyl-N-((C₇-C₁₆)Aralkyloxy-(C₁- C₁₀)alkyl)carbamoyl, CON(CH₂)h, worin eine CH₂-Gruppe durch O, S, N-(C₁-C₈)Alkylimino, N-(C₃-C₈)-Cycloalkylimino, N-(C₃-C₈)- Cycloalkyl-(C₁-C₄)alkylimino, N-(C₆-C₁₂)-Arylimino, N-(C₇-C₁₆)- Aralkylimino oder N-(C₁-C₄)-Alkoxy-(C₁-C₆)-alkylimino ersetzt sein kann und h 3 bis 7 bedeutet,
Carbamoyloxy, N-(C₁-C₁₂)-Alkylcarbamoyloxy, N, N-Di- (C₁-C₁₂)-alkylcarbamoyloxy, N-(C₃-C₈)-Cycloalkylcarbamoyloxy, N-(C₆-C₁₂)-Arylcarbamoyloxy, N-(C₇-C₁₆)-Aralkylcarbamoyloxy, N-(C₁-C₁₀)-Alkyl-N-(C₆-C₁₂)arylcarbamoyloxy, N-(C₁-C₁₀)-Alkyl-N- (C₇-C₁₆)-Aralkylcarbamoyloxy, N-((C₁-C₁₀)alkyl))carbamoyloxy, N-((C₆-C₁₂)-Aryloxy-(C₁-C₁₀)alkyl)carbamoyloxy, N-((C₇-C₁₆)-Aralkyloxy-(C₁-C₁₀)alkyl)carbamoyloxy, N-(C₁-C₁₀)-Alkyl-N-((C₁-C₁₀)-Alkoxy-(C₁-C₁₀)alkyl)carbamoyloxy, N-(C₁-C₁₀)-Alkyl-N-((C₆-C₁₂)-Aryloxy-(C₁-C₁₀)alkyl)carbamoyloxy, N-(C₁-C₁₀)-Alkyl-N-((C₇-C₁₆)-Aralkyloxy- (C₁-C₁₀)alkyl)carbamoyloxy,
Amino, (C₁-C₁₂)-Alkylamino, Di-(C₁-C₁₂)alkylamino, (C₃-C₈)- Cycloalkylamino, (C₃-C₁₂)-Alkenylamino, (C₃-C₁₂)-Alkinylamino, N-(C₆-C₁₂)-Arylamino, N-(C₇-C₁₁)-Aralkylamino, N-Alkyl- Aralkylamino, N-Alkyl-Arylamino, (C₁-C₁₂)-Alkoxyamino, (C₁-C₁₂)- Alkoxy-N-(C₁-C₁₀)-alkylamino,
(C₁-C₁₂)-Alkanoylamino, (C₃-C₈)-Cycloalkanoylamino, (C₆-C₁₂)- Aroylamino, (C₇-C₁₆)-Aralkanoylamino, (C₁-C₁₂)-Alkanoyl-N- (C₁-C₁₀)-alkylamino, (C₃-C₈)-Cycloalkanoyl-N-(C₁-C₁₀)-alkylamino, (C₆-C₁₂)-Aroyl-N-(C₁-C₁₀)alkylamino, (C₇-C₁₁)-Aralkanoyl-N- (C₁-C₁₀)-alkylamino,
(C₁-C₁₂)-Alkanoylamino-(C₁-C₈)-alkyl, (C₃-C₈)-Cycloalkanoylamino- (C₁-C₈)alkyl, (C₆-C₁₂)-Aroylamino-(C₁-C₈)-alkyl, (C₇-C₁₆)- Aralkanoylamino-(C₁-C₈)-alkyl, Amino-(C₁-C₁₀)-alkyl, N-(C₁-C₁₀)alkylamino-(C₁-C₁₀)alkyl, N,N-Di-(C₁-C₁₀)alkylamino-(C₁- C₁₀)alkyl, (C₃-C₈)cycloalkylamino-(C₁-C₁₀)alkyl, (C₁-C₁₂)-Alkylmercapto, (C₁-C₁₂)-Alkylsulfinyl, (C₁-C₁₂)- Alkylsulfonyl, (C₆-C₁₂)-Arylmercapto, (C₆-C₁₂)-Arylsulfinyl, (C₆-C₁₂)-Arylsulfonyl, (C₇-C₁₆)-Aralkylmercapto, (C₇-C₁₆)- Aralkylsulfinyl, (C₇-C₁₆)-Aralkylsulfonyl,
Sulfamoyl, N-(C₁-C₁₀)-Alkylsulfamoyl, N,N-Di-(C₁-C₁₀)- alkylsulfamoyl, (C₃-C₈-cycloalkylsulfamoyl, N-(C₆-(C₁₂)- Arylsulfamoyl, N-(C₇-C₁₆)-Aralkylsulfamoyl, N-(C₁-C₁₀)-Alkyl-N-(C₆-C₁₂)-Arylsulfamoyl, N-(C₁-C₁₀)-Alkyl-N-(C₇-C₁₆)-Aralkylsulfamoyl, (C₁-C₁₀)-Alkyl-sulfonamido, N-((C₁-C₁₀)alkyl)-(C₁- C₁₀)alkylsulfonamido, (C₇-C₁₆)-Aralkylsulfonamido, N-((C₁- C₁₀)alkyl-(C₇-C₁₆)-AralkylsuIfonamido, bedeuten, wobei die Reste, die einen Arylrest enthalten ihrerseits am Aryl substituiert sein können durch 1 bis 5 gleiche oder verschiedene Reste aus der Reihe:
Hydroxy, Halogen, Cyano, Trifluormethyl, Nitro, Carboxy, (C₁-C₁₂)- Alkyl, (C₃-C₈)-Cycloalkyl, (C₆-C₁₂)-Aryl, (C₇-C₁₆)-Aralkyl, (C₁ -C₁₂)- Alkoxy, (C₁-C₁₂)-Alkoxy-(C₁-C₁₂)alkyl, (C₁-C₁₂)-Alkoxy- (C₁-C₁₂)alkoxy, (C₆-C₁₂)-Aryloxy, (C₇-C₁₆)-Aralkyloxy, (C₁-C₈)- Hydroxyalkoyl,
(C₁-C₁₂)-Alkylcarbonyl, (C₃-C₈)-Cycloalkylcarbonyl, (C₆-C₁₂)- Arylcarbonyl, (C₇-C₁₆)-Aralkylcarbonyl,
(C₁-C₁₂)-Alkoxycarbonyl, (C₁-C₁₂)-Alkoxy-(C₁-C₁₂)-alkoxycarbonyl, (C₆-C₁₂)-Aryloxycarbonyl, (C₇-C₁₆)-Aralkoxycarbonyl, (C₃-C₈)- Cycloalkoxycarbonyl, (C₂-C₁₂)-Alkenyloxycarbonyl, (C₂-C₁₂)- Alkinyloxycarbonyl,
(C₁-C₁₂)-Alkylcarbonyloxy, (C₃-C₈)-Cycloalkylcarbonyloxy, (C₆-C₁₂)-Arylcarbonyloxy, (C₇-C₁₆)-Aralkylcarbonyloxy, Cinnamoyloxy, (C₂-C₁₂)-Alkenylcarbonyloxy, (C₂-C₁₂)- Alkinylcarbonyloxy,
(C₁-C₁₂)-Alkoxycarbonyloxy, (C₁-C₁₂)-Alkoxy-(C₁-C₁₂)- alkoxycarbonyloxy, (C₆-C₁₂)-Aryloxycarbonyloxy, (C₇-C₁₆)- Aralkyloxycarbonyloxy, (C₃-C₈)-Cycloalkoxycarbonyloxy, (C₂-C₁₂)- Alkenyloxycarbonyloxy, (C₂-C₁₂)-Alkinyloxycarbonyloxy,
Carbamoyl, N-(C₁-C₁₂)-Alkylcarbamoyl, N, N-Di-(C₁-C₁₂)- alkylcarbamoyl, N-(C₃-C₈)-Cycloalkylcarbamoyl, N,N-Dicyclo (C₃-C₈)-alkylcarbamoyl, N-(C₁-C₁₀)-Alkyl-N-(C₃-C₈)- Cycloalkylcarbamoyl, N-((C₃-C₈)-Cycloalkyl-(C₁-C₆)- alkyl)carbamoyl, N-(C₁-C₆)-Alkyl-N-((C₃-C₈-Cycloalkyl-(C₁-C₆)- alkyl)carbamoyl, N-(+)-Dehydroabietylcarbamoyl, N-(C₁-C₆)-Alkyl- N-Dehydroabietylcarbamoyl, N-(C₆-C₁₂)-Arylcarbamoyl, N-(C₇-C₁₆)- Aralkylcarbamoyl, N-(C₁-C₁₀)-Alkyl-N-(C₆-C₁₆)arylcarbamoyl, N- (C₁-C₁₀)-Alkyl-N-(C₇-C₁₆)-Aralkylcarbamoyl, N-((C₁-C₁₀)-Alkoxy- (C₁-C₁₀)alkyl)carbamoyl, N-((C₆-C₁₆)-Aryloxy-(C₁- C₁₀)alkyl)carbamoyl, N-((C₇-C₁₆)-Aralkyloxy-(C₁- C₁₀)alkyl)carbamoyl, N-(C₁-C₁₀)-Alkyl-N-((C₁-C₁₀)-Alkoxy-(C₁- C₁₀)alkyl)carbamoyl, N-(C₁-C₁₀)-Alkyl-N-((C₆-C₁₂)-Aryloxy-(C₁- C₁₀)alkyl)carbamoyl, N-(C₁-C₁₀)-Alkyl-N-((C₇-C₁₆)Aralkyloxy-(C₁- C₁₀)alkyl)carbamoyl, CON(CH₂)h worin eine CH₂-Gruppe durch O, S, N-(C₁-C₈)Alkylimino, N-(C₃-C₈)-Cycloalkylimino, N-(C₃-C₈)- Cycloalkyl-(C₁-C₄)alkylimino, N-(C₆-C₁₂)-Arylimino, N-(C₇-C₁₆) Aralkylimino oder N-(C₁-C₄)-Alkoxy-(C₁-C₆)-alkylimino ersetzt sein kann und h 3 bis 7 bedeutet,
Carbamoyloxy, N-(C₁-C₁₂)-Alkylcarbamoyloxy, N,N-Di-(C₁-C₁₂)- alkylcarbamoyloxy, N-(C₃-C₈)-Cycloalkylcarbamoyloxy, N-(C₆-C₁₆)- Arylcarbamoyloxy, N-(C₇-C₁₆)-Aralkylcarbamoyloxy, N-(C₁-C₁₀)- Alkyl-N-(C₆-C₁₂)arylcarbamoyloxy, N-(C₁-C₁₀)-Alkyl-N-(C₇-C₁₆)- Aralkylcarbamoyloxy, N-((C₁-C₁₀)alkyl))carbamoyloxy, N-((C₆-C₁₂)-Aryloxy-(C₁-C₁₀)alkyl)carbamoyloxy, N-((C₇-C₁₆)-Aralkyloxy-(C₁-C₁₀)alkyl)carbamoyloxy, N-(C₁-C₁₀)-Alkyl-N-((C₁-C₁₀)-Alkoxy-(C₁-C₁₀)alkyl)carbamoyloxy, N-(C₁-C₁₀)-Alkyl-N-((C₆-C₁₂)-Aryloxy-(C₁-C₁₀)alkyl)carbamoyloxy, N-(C₁-C₁₀)-Alkyl-N-((C₇-C₁₆)-Aralkyloxy- (C₁-C₁₀)alkyl)carbamoyloxy,
Amino, (C₁-C₁₂)-Alkylamino, Di-(C₁-C₁₂)alkylamino, (C₃-C₈)- Cycloalkylamino, (C₃-C₁₂)-Alkenylamino, (C₃-C₁₂)-Alkinylamino, N- (C₆-C₁₂)-Arylamino, N-(C₇-C₁₁)-Aralkylamino, N-Alkyl- Aralkylamino, N-Alkyl-Arylamino, (C₁-C₁₂)-Alkoxyamino, (C₁-C₁₂)- Alkoxy-N-(C₁-C₁₀)-alkylamino,
(C₁-C₁₂)-Alkanoylamino, (C₃-C₈)-Cycloalkanoylamino, (C₆-C₁₂)-Aroylamino, (C₇-C₁₆)-Aralkanoylamino, (C₁-C₁₂)-Alkanoyl- N-(C₁-C₁₀)-alkylamino, (C₃-C₈)-Cycloalkanoyl-N-(C₁-C₁₀)- alkylamino, (C₆-C₁₂)-Aroyl-N-(C₁-C₁₀)alkylamino, (C₇-C₁₁)- Aralkanoyl-N-(C₁-C₁₀)-alkylamino,
(C₁-C₁₂)-Alkanoylamino-(C₁-C₈)-alkyl, (C₃-C₈)-Cycloalkanoylamino- (C₁-C₈)alkyl, (C₆-C₁₂)-Aroylamino- (C₁-C₈)-alkyl, (C₇-C₁₆)-Aralkanoylamino-(C₁-C₈)-alkyl, Amino- (C₁-C₁₀)-alkyl, N-(C₁-C₁₀)alkylamino-(C₁-C₁₀)alkyl, N,N-Di- (C₁-C₁₀)alkylamino (C₁-C₁₀)alkyl, (C₃-C₈)Cycloalkylamino (C₁- C₁₀)alkyl,
(C₁-C₁₂)-Alkylmercapto, (C₁-C₁₂)-Alkylsulfinyl, (C₁-C₁₂)- Alkylsulfonyl, (C₆-C₁₆)-Arylmercapto, (C₆-C₁₆)-Arylsulfinyl, (C₆- C₁₆)-Arylsulfonyl, (C₇-C₁₆)-Aralkylmercapto, (C₇-C₁₆)- Aralkylsulfinyl, (C₇-C₁₆)-Aralkylsulfonyl,
R¹ und R² oder R² und R³ eine Kette [CH₂]o bilden, in welcher eine oder zwei CH₂-Gruppen der gesättigten oder mit einer C=C-Doppelbindung ungesättigten Kette gegebenenfalls durch O, S, SO, SO₂ oder NR′ ersetzt sind, o = 3, 4 oder 5 bedeutet und R′ Wasserstoff, (C₆-C₁₂)-Aryl, (C₁-C₈)-Alkyl, (C₁- C₈)-Alkoxy-(C₁-C₈)alkyl, (C₇-C₁₂)-Aralkoxy-(C₁-C₈)alkyl, (C₆-C₁₂)-Aryloxy-(C₁- C₈)-alkyl, (C₁-C₁₀)-Alkanoyl, ggf. substituiertes (C₇-C₁₆)-Aralkanoyl, ggf. substituiertes (C₆-C₁₂)-Aroyl bedeuten, oder
einen carbocylischen oder einen heterocyclischen, gegebenenfalls mit Fluor, Chlor, (C₁-C₈)-Alkoxy oder einem Carbamoyl-Rest substituierten 5- oder 6 gliedrigen aromatischen Ring bilden,
R⁴ einen verzweigten oder unverzweigten (C₁-C₂₀)-Alkylrest oder einen Arylrest oder einen Heteroarylrest bedeutet,
wobei diese Reste substituiert sind mit einem oder mehreren Resten aus der Reihe
(C₂-C₁₂)-Alkenyl, (C₂-C₁₂)-Alkinyl, (C₆-C₁₂)-Aryl, Heteroaryl, (C₆-C₁₂)-Aralkyloxy, Heteroalkyloxy, Wasserstoff, Hydroxy, Halogen, Cyano, Trifluormethyl, Nitro, Carboxy, (C₁-C₁₂)-Alkyl, (C₃-C₈)-Cycloalkyl, (C₆-C₁₂)-Aryl, (C₇-C₁₆)-Aralkyl, (C₂-C₁₂)-Alkenyl, (C₂-C₁₂)-Alkinyl, (C₁-C₁₂)-Alkoxy, (C₃-C₈)- Cycloalkoxy, (C₁-C₁₂)-Alkoxy-(C₁-C₁₂)alkyl, (C₁-C₁₂)-Alkoxy-(C₁-C₁₂)alkoxy, (C₆-C₁₂)-Aryloxy, (C₇-C₁₆)-Aralkyloxy, (C₆-C₁₂)-Aryloxy-(C₁-C₆)-alkoxy, (C₇- C₁₆)-Aralkoxy-(C₁-C₆)-alkoxy, -O-[CH2-]xCfH(2f+1-g)Fg, -OCF₂Cl, -OCF₂-CHFCl,
(C₁-C₁₂)-Alkylcarbonyl, (C₃-C₈)-Cycloalkylcarbonyl, (C₆-C₁₂)-Arylcarbonyl, (C₇-C₁₆)-Aralkylcarbonyl, Cinnamoy, (C₂-C₁₂) Alkenylcarbonyl, (C₂-C₁₂)-Alkinylcarbonyl,
(C₁-C₁₂)-Alkoxycarbonyl, (C₁-C₁₂)-Alkoxy-(C₁-C₁₂)-alkoxycarbonyl, (C₆-C₁₂)- Aryloxycarbonyl, (C₇-C₁₆)-Aralkoxycarbonyl, (C₃-C₈)-Cycloalkoxycarbonyl, (C₂- C₁₂)-Alkenyloxycarbonyl, (C₂-C₁₂)-Alkinyloxycarbonyl,
(C₁-C₁₂)-Alkylcarbonyloxy, (C₃-C₈)-Cycloalkylcarbonyloxy, (C₆-C₁₂)-Arylcarbonyloxy, (C₇-C₁₆)-Aralkylcarbonyloxy, Cinnamoyloxy, (C₂- C₁₂)-Alkenylcarbonyloxy, (C₂-C₁₂)-Alkinylcarbonyloxy,
(C₁-C₁₂)-Alkoxycarbonyloxy, (C₁-C₁₂)-Alkoxy-(C₁-C₁₂)-alkoxycarbonyloxy, (C₆-C₁₂)-Aryloxycarbonyloxy, (C₇-C₁₆)-Aralkyloxycarbonyloxy, (C₂-C₈)- Cycloalkoxycarbonyloxy, (C₂-C₁₂)-Alkenyloxycarbonyloxy, (C₂-C₁₂)- Alkinyloxycarbonyloxy,
Carbamoyl, N-(C₁-C₁₂)-Alkylcarbamoyl, N,N-Di-(C₁-C₁₂)-alkylcarbamoyl, N- (C₃-C₈)-Cycloalkylcarbamoyl, N,N-Dicyclo(C₃-C₈)-alkylcarbamoyl, N-(C₁-C₁₀)- Alkyl-N-(C₃-C₈)-Cycloalkylcarbamoyl, N-(C₃-C₈)-Cycloalkyl-(C₁-C₆)- alkyl)carbamoyl, N-(C₁-C₆)-Alkyl-N-((C₃-C₈-Cycloalkyl-(C₁-C₆)-alkyl)carbamoyl, N-(+)-Dehydroabietylcarbamoyl, N-(C₁-C₆)-Alkyl-N-Dehydroabietylcarbamoyl, N- (C₆-C₁₂)-Arylcarbamoyl, N-(C₇-C₁₆)-Aralkylcarbamoyl, N-(C₁-C₁₀)-Alkyl-N-(C₆- C₁₆)arylcarbamoyl, N-(C₁-C₁₀)-Alkyl-N-(C₇-C₁₆)-Aralkylcarbamoyl, N-((C₁-C₁₀)- Alkoxy-(C₁-C₁₀)alkyl)carbamoyl, N-((C₆-C₁₆)-Aryloxy-(C₁-C₁₀)alkyl)carbamoyl, N-((C₇-C₁₆)-Aralkyloxy-(C₁-C₁₀)alkyl)carbamoyl,N-(C₁-C₁₀)-Alkyl-N-((-C₁-C₁₀)- Alkoxy-(C₁-C₁₀)alkyl)carbamoyl, N-( C₁-C₁₀)-Alkyl-N-((C₆-C₁₂)-Aryloxy-(C₁- C₁₀)alkyl)carbamoyl, N-(C₁-C₁₀)-Alkyl-N-((C₇-C₁₆)Aralkyloxy-(C₁- C₁₀)alkyl)carbamoyl, CON(CH₂)h, worin eine CH₂-Gruppe durch O, S, N-(C₁- C₈)Alkylimino, N-(C₃-C₈)-Cycloalkylimino, N-(C₃-C₈)-Cycloalkyl-(C₁- C₄)alkylimino, N-(C₆-C₁₂)-Arylimino, N-(C₇-C₁₆)-Aralkylimino oder N-(C₁-C₄)- Alkoxy-(C₁-C₆)-alkylimino ersetzt sein kann und h 3 bis 7 bedeutet, Carbamoyloxy, N-(C₁-C₁₂)-Alkylcarbamoyloxy, N,N-Di-(C₁-C₁₂)- alkylcarbamoyloxy, N-(C äC₈)-Cycloalkylcarbamoyloxy, N-(C₆-C₁₂)- Arylcarbamoyloxy, N-(C₇-C₁₆)-Aralkylcarbamoyloxy, N-(C₁-C₁₀)-Alkyl-N-(C₆- C₁₂)arylcarbamoyloxy, N-(C₁-C₁₀)-Alkyl-N-(C₇-C₁₆)-Aralkylcarbamoyloxy, N-((C₁-C₁₀)alkyl)carbamoyloxy, N-((C₆-C₁₂)-Aryloxy-(C₁- C₁₀)alkyl)carbamoyloxy, N-((C₇-C₁₆)-Aralkyloxy-(C₁-C₁₀)alkyl)carbamoyloxy, N-(C₁-C₁₀)-Alkyl-N-((C₁-C₁₀)-Alkoxy-(C₁-C₁₀)alkyl)carbamoyloxy, N-(C₁-C₁₀)-Alkyl-N-((C₆-C₁₆)-Aryloxy-(C₁-C₁₀)alkyl)carbamoyloxy, N-(C₁-C₁₀)-Alkyl-N-((C₇-C₁₆)-Aralkyloxy-(C₁-C₁₀)alkyl)carbamoyloxy,
Amino, (C₁-C₁₂)-Alkylamino, Di-(C₁-C₁₂)alkylamino, (C₃-C₈)-Cycloalkylamino, (C₃-C₁₂)-Alkenylamino, (C₃-C₁₂)-Alkinylamino, N-(C₆-C₁₂)-Arylamino, N-(C₇- C₁₁)-Aralkylamino, N-Alkyl-Aralkylamino, N-Alkyl-Arylamino, (C₁-C₁₂)- Alkoxyamino, (C₁-C₁₂)-Alkoxy-N-(C₁-C₁₀)-alkylamino,
(C₁-C₁₂)-Alkanoylamino, (C₃-C₈)-Cycloalkanoylamino, (C₆-C₁₂)-Aroylamino, (C₇-C₁₆)-Aralkanoylamino, (C₁-C₁₂)-Alkanoyl-N-(C₁-C₁₀)-alkylamino, (C₃-C₈)- Cycloalkanoyl-N-(C₁-C₁₀)-alkylamino, (C₆-C₁₂)-Aroyl-N-(C₁-C₁₀)alkylamino, (C₇- C₁₁)-Aralkanoyl-N-(C₁-C₁₀)-alkylamino,
(C₁-C₁₂)-Alkanoylamino-(C₁-C₈)-alkyl, (C₃-C₈)-Cycloalkanoylamino-(C₁-C₈)alkyl, (C₆-C₁₆)-Aroylamino-(C₁-C₈)-alkyl, (C₇-C₁₆)-Aralkanoylamino-(C₁-C₈)-alkyl, Amino-(C₁-C₁₀)-alkyl, N-(C₁-C₁₀)alkylamino-(C₁-C₁₀)alkyl, N,N-Di-(C₁- C₁₀)alkylamino (C₁-C₁₀)alkyl, (C₃-C₈)cycloalkylamino-(C₁-C₁₀) alkyl,
(C₁-C₁₂)-Alkylmercapto, (C₁-C₁₂)-Alkylsulfinyl, (C₁-C₁₂)-AlkylsuIfonyl, (C₆-C₁₂)- Arylmercapto, (C₆-C₁₆)-Arylsulfinyl, (C₆-C₁₆)-Arylsulfonyl, (C₇-C₁₆)- Aralkylmercapto, (C₇-C₁₆)-Aralkylsulfinyl, (C₇-C₁₆)-Aralkylsulfonyl, Sulfamoyl, N-(C₁-C₁₀)-Alkylsulfamoyl, N,N-Di-(C₁-C₁₀)-alkylsulfamoyl, (C₃-C₈)- Cycloalkylsulfamoyl, N-(C₆-(C₁₂)-Arylsulfamoyl, N-(C₇-C₁₆)-Aralkylsulfamoyl, N-(C₁-C₁₀)-Alkyl-N-(C₆-C₁₂)-Arylsulfamoyl, N-(C₁-C₁₀)-Alkyl-N-(C₇-C₁₆)- Aralkylsulfamoyl, (C₁-C₁₀)-Alkyl-sulfonamido, N-((C₁-C₁₀)alkyl)-(C₁- C₁₀)alkylsulfonamido, (C₇-C₁₆)-Aralkylsulfonamido, N-((C₁-C₁₀)alkyl-(C₇-C₁₆)- Aralkylsulfonamido,
wobei die Reste, die einen Arylrest enthalten ihrerseits am Aryl substituiert sein können durch 1 bis 5 gleiche oder verschiedene Reste aus der Reihe: Hydroxy, Halogen, Cyano, Trifluormethyl, Nitro, Carboxy, (C₁-C₁₂)-Alkyl, (C₃-C₈)-Cycloalkyl, (C₆-C₁₂)-Aryl, (C₇-C₁₆)-Aralkyl, (C₁-C₁₂)-Alkoxy, (C₁-C₁₂)- Alkoxy-(C₁-C₁₂)alkyl, (C₁-C₁₂)-Alkoxy-(C₁-C₁₂)alkoxy, (C₆-C₁₂)-Aryloxy, (C₇-C₁₆)-Aralkyloxy, (C₁-C₈)-Hydroxyalkoxy,
(C₁-C₁₂)-Alkylcarbonyl, (C₃-C₈)-Cycloalkylcarbonyl, (C₆-C₁₂)-Arylcarbonyl, (C₇- C₁₆)-Aralkylcarbonyl und,
sofern Q NR′ bedeutet, so steht R⁴ in der Bedeutung von R′′, wobei R′ und R′′ gleich oder verschieden sind und Wasserstoff, (C₆-C₁₂)-Aryl, (C₁-C₈)- Alkyl, (C₁-C₈)-Alkoxy-(C₁-C₈)alkyl, (C₇-C₁₂)-Aralkoxy-(C₁-C₈)alkyl, (C₆-C₁₂)- Aryloxy-(C₁-C₈)-alkyl, (C₁-C₁₀)-Alkanoyl, ggf. substituiertes (C₇-C₁₆)-Aralkanoyl, ggf. substituiertes (C₆-C₁₂)-Aroyl bedeuten, oder
R′ und R′′ gemeinsam für -[CH₂]h stehen, worin eine CH₂-Gruppe durch O, S, N-Acylimino oder N-(C₁-C₁₀)-Alkoxycarbonylimino ersetzt sein kann, undf = 1 bis 8,
g = 0, 1 bis (2f+1),
x = 0 bis 3,
h = 3 bis 6 bedeuteneinschließlich der physiologisch wirksamen Salze, wobei 3-Benzyloxypyridin-2-carbonsäure-L-threonylamid und 3-Benzyloxy- pyridin-2-carbonsäure-((Fmoc-Phg)L-threonyl)amid-Hydrochlorid ausgenommen sind.1. Compounds of the general formula I in which
QO, S and NR ′,
XO and S,
Y C-R³ or N,
m 0 and 1,
A (C₁-C₄) alkylene, which is optionally substituted with one or two substituents from the series halogen, cyano, nitro, trifluoromethyl, (C₁-C₆) alkyl, (C₁-C₆) hydroxyalkyl, (C₁-C₆) -Alkoxy, -O- [CH₂] x -C f H (2f + 1-g) Hal g , preferably (C₁-C₈) fluoroalkoxy, (C₁-C₈) fluoroalkenyloxy, (C₁-C₈) fluoroalkynyloxy, - OCF₂Cl or -O-CF₂-CHFCl, (C₁-C₆) alkyl mercapto, (C₁-C₆) alkylsulfinyl, (C₁-C₆) alkylsulfonyl, (C₁-C₆) alkylcarbonyl, (C₁-C₆) alkoxycarbonyl, carbamoyl , N- (C₁-C₄) alkylcarbamoyl, N, N-di- (C₁-C₄) alkylcarbamoyl, (C₁-C₆) alkylcarbonyloxy, (C₃-C₈) cycloalkyl, phenyl, benzyl, phenoxy, benzyloxy, anilino , N-methylanilino, phenylmercapto, phenylsulfonyl, phenylsulfinyl, sulfamoyl, N- (C₁-C₄) alkylsulfamoyl, N, N-di- (C₁-C₄) alkylsulfamoyl, or
with a substituted (C₆-C₁₂) aryloxy, (C₇-C₁₁) aralkyloxy, (C₆-C₁₂) aryl or (C₇-C₁₁) aralkyl radical which is in the aryl part 1, 2, 3, 4 or 5 identical or different substituents from the series halogen, cyano, nitro, trifluoromethyl, (C₁-C₆) alkyl, (C₁-C₆) alkoxy, -O- [CH₂] x -C f H (2f + 1-g) Hal g , -OCF₂Cl, -O-CF₂-CHFCl, (C₁-C₆) -alkylmercapto, (C₁-C₆) -alkylsulfinyl, (C₁-C₆) -alkylsulfonyl, (C₁-C₆) -alkylcarbonyl, (C₁-C₆) -Alkoxycarbonyl, carbamoyl, N- (C₁-C₄) alkylcarbamoyl, N, N-di- (C₁-C₄) alkylcarbamoyl, (C₁-C₆) alkylcarbonyloxy, (C₃-C₈) cycloalkyl, sulfamoyl, N- ( C₁-C₄) - alkylsulfamoyl or N, N-di- (C₁-C₄) alkylsulfamoyl, or
with the substituents R⁵ of the α-C atom of an α-amino acid, whereby the natural L-amino acids and their D-isomers can be used;
B is an acidic group from the series -CO₂H, -CONHCOR ''',-CONHSOR''', CONHSO₂RW ''', -NHSO₂CF₃, tetrazolyl, imidazolyl or 3-hydroxyisoxazolyl, where R''' aryl, heteroaryl, (C₃ -C₇) - cycloalkyl or (C₁-C₄) alkyl, optionally monosubstituted with (C₆- C₁₂) aryl, heteroaryl, OH, SH, (C₁-C₄) alkyl, (C₁-C₄) alkoxy, (C₁- C₄) - Thioalkyl, sulfinyl or sulfonyl, CF₃, Cl, Br, F, I, NO₂, -COOH, (C₂-C₅) - alkoxycarbonyl, NH₂, mono- or di- (C₁-C₄-alkyl) amino or (C₁-C₄) - perfluoroalkyl means
R¹, R² and R³ are the same or different and are hydrogen, hydroxy, halogen, cyano, trifluoromethyl, nitro, carboxy, (C₁-C₁₂) alkyl, (C₃-C₈) cycloalkyl, (C₃-C₈) cycloalkyl- (C₁ -C₁₂) alkyl, (C₃-C₈) cycloalkoxy, (C₃-C₈) cycloalkyl- (C₁-C₁₂) alkoxy, (C₃-C₈) cycloalkyloxy- (C₁-C₁₂) alkyl, (C₃-C₈ ) -Cycloalkyloxy- (C₁-C₁₂) -alkoxy, (C₃-C₈) -cycloalkyl- (C₁-C₈) -alkyl- (C₁-C₆) -alkoxy, (C₃-C₈) -cycloalkyl- (C₁-C₈) - alkoxy- (C₁- C₆) alkyl, (C₃-C₈) cycloalkyloxy- (C₁-C₈) alkoxy- (C₁-C₆) alkyl, (C₃- C₈) cycloalkoxy- (C₁-C₈) alkoxy- (C₁-C₈) alkoxy, (C₆-C₁₂) aryl, (C₇- C₁₆) aralkyl, (C₂-C₁₂) alkenyl, (C₂-C₁₂) alkynyl, (C₁-C₁₂) alkoxy, (C₁ -C₁₂) alkoxy- (C₁-C₁₂) alkyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxy, (C₁-C₁₂) alkoxy- (C₁-C₈) alkoxy- (C₁-C₈) - alkyl, (C₆-C₁₂) aryloxy, (C₇-C₁₆) aralkyloxy, (C₆-C₁₂) aryloxy- (C₁-C₆) alkoxy, (C₇-C ₆) - Aralkoxy- (C₁-C₆) alkoxy, (C₁-C₈) hydroxyalkyl, (C₆-C₁₆) aryloxy- (C₁-C₈) alkyl, (C₇-C₁₆) aralkoxy- (C₁-C₈) -alkyl, (C₆-C₁₂) aryloxy- (C₁-C₈) alkoxy- (C₁-C₆) alkyl, (C₇-C₁₂) aralkyloxy- (C₁-C₈) alkoxy- (C₁-C₆) alkyl , -O- [CH 2- ] x C f H (2f + 1-g) F g , -OCF₂Cl, -OCF₂-CHFCl,
(C₁-C₁₂) alkylcarbonyl, (C₃-C₈) cycloalkylcarbonyl, (C₆-C₁₂) arylcarbonyl, (C₇-C₁₆) aralkylcarbonyl, cinnamoyl, (C₂-C₁₂) alkenylcarbonyl, (C₂-C₁₂) alkynylcarbonyl,
(C₁-C₁₂) alkoxycarbonyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyl, (C₆-C₁₂) aryloxycarbonyl, (C₇-C₁₆) aralkoxycarbonyl, (C₃-C₁₀) - cycloalkoxycarbonyl, (C₂ -C₁₂) alkenyloxycarbonyl, (C₂-C₁₂) alkynyloxycarbonyl,
(C₁-C₁₂) alkylcarbonyloxy, (C₃-C₈) cycloalkylcarbonyloxy, (C₆-C₁₂) arylcarbonyloxy, (C₇-C₁₆) aralkylcarbonyloxy, cinnamoyloxy, (C₂-C₁₂) alkenylcarbonyloxy, (C₂-C₁₂), alkynylcarbonyloxy
(C₁-C₁₂) alkoxycarbonyloxy, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyloxy, (C₆-C₁₂) aryloxycarbonyloxy, (C₇-C₁₆) aralkyloxycarbonyloxy, (C₃-C₈) cycloalkoxycarbonyloxy, (C₂ -C₁₂) - alkenyloxycarbonyloxy, (C₂-C₁₂) alkynyloxycarbonyloxy,
Carbamoyl, N- (C₁-C₁₂) alkylcarbamoyl, N, N-di- (C₁-C₁₂) alkylcarbamoyl, N- (C₃-C₈) -cycloalkylcarbamoyl, N, N-dicyclo (C₃-C₈) -alkylcarbamoyl, N - (C₁-C₁₀) alkyl-N- (C₃-C₈) - cycloalkylcarbamoyl, N - ((C₃-C₈) cycloalkyl- (C₁-C₆) - alkyl) carbamoyl, N- (C₁-C₆) alkyl- N - ((C₃-C₈-cycloalkyl- (C₁-C₆) - alkyl) carbamoyl, N - (+) - dehydroabietylcarbamoyl, N- (C₁-C₆) alkyl- N-dehydroabietylcarbamoyl, N- (C₆-C₁₂) - Arylcarbamoyl, N- (C₇-C₁₆) aralkylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₆) arylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₇-C₁₆) aralkylcarbamoyl , N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N - ((C₆-C₁₆) aryloxy (C₁- C₁₀) alkyl) carbamoyl, N - ((C₇-C₁₆) aralkylox - (C₁- C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₁-C₁₀) alkoxy- (C₁- C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl- N - ((C₆-C₁₂) aryloxy- (C₁- C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₇-C₁₆) aralkyloxy- (C - C₁₀) -alkyl) carbamoyl, CON (CH₂) h, in which a CH₂ group replaced by O, S, N- (C₁-C₈) alkylimino, N- (C₃-C₈) -Cycloalkylimino, N- (C₃-C₈) - Cycloalkyl- (C₁-C₄) alkylimino, N- (C₆-C₁₂) arylimino, N- (C₇-C₁₆) aralkylimino or N- (C₁-C₄) alkoxy- (C₁-C₆) alkylimino can be replaced and h means 3 to 7,
Carbamoyloxy, N- (C₁-C₁₂) alkylcarbamoyloxy, N, N-Di- (C₁-C₁₂) alkylcarbamoyloxy, N- (C₃-C₈) cycloalkylcarbamoyloxy, N- (C₆-C₁₂) arylcarbamoyloxy, N- (C₇ -C₁₆) aralkylcarbamoyloxy, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₂) arylcarbamoyloxy, N- (C₁-C₁₀) alkyl-N- (C₇-C₁₆) aralkylcarbamoyloxy, N - ((C₁ -C₁₀) alkyl)) carbamoyloxy, N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀) alkyl) carbamoyloxy, N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₂) aryloxy- ( C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyloxy,
Amino, (C₁-C₁₂) alkylamino, di- (C₁-C₁₂) alkylamino, (C₃-C₈) cycloalkylamino, (C₃-C₁₂) alkenylamino, (C₃-C₁₂) alkynylamino, N- (C₆-C₁₂) -Arylamino, N- (C₇-C₁₁) aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C₁-C₁₂) alkoxyamino, (C₁-C₁₂) - alkoxy-N- (C₁-C₁₀) alkylamino ,
(C₁-C₁₂) alkanoylamino, (C₃-C₈) cycloalkanoylamino, (C₆-C₁₂) aroylamino, (C₇-C₁₆) aralkanoylamino, (C₁-C₁₂) alkanoyl-N- (C₁-C₁₀) alkylamino, (C₃-C₈) cycloalkanoyl-N- (C₁-C₁₀) alkylamino, (C₆-C₁₂) aroyl-N- (C₁-C₁₀) alkylamino, (C₇-C₁₁) aralkanoyl-N- (C₁-C₁₀) -alkylamino,
(C₁-C₁₂) alkanoylamino- (C₁-C₈) alkyl, (C₃-C₈) -cycloalkanoylamino- (C₁-C₈) alkyl, (C₆-C₁₂) aroylamino- (C₁-C₈) alkyl, (C₇- C₁₆) - aralkanoylamino- (C₁-C₈) alkyl, amino- (C₁-C₁₀) alkyl, N- (C₁-C₁₀) alkylamino- (C₁-C₁₀) alkyl, N, N-di- (C₁-C₁₀) alkylamino- (C₁- C₁₀) alkyl, (C₃-C₈) cycloalkylamino- (C₁-C₁₀) alkyl, (C₁-C₁₂) alkylmercapto, (C₁-C₁₂) alkylsulfinyl, (C₁-C₁₂) alkylsulfonyl, (C₆- C₁₂) arylmercapto, (C₆-C₁₂) arylsulfinyl, (C₆-C₁₂) arylsulfonyl, (C₇-C₁₆) aralkylmercapto, (C₇-C₁₆) aralkylsulfinyl, (C₇-C₁₆) aralkylsulfonyl,
Sulfamoyl, N- (C₁-C₁₀) alkylsulfamoyl, N, N-di- (C₁-C₁₀) alkylsulfamoyl, (C₃-C₈-cycloalkylsulfamoyl, N- (C₆- (C₁₂) arylsulfamoyl, N- (C₇-C₁₆ ) Aralkylsulfamoyl, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₂) arylsulfamoyl, N- (C₁-C₁₀) alkyl-N- (C₇-C₁₆) aralkylsulfamoyl, (C₁-C₁₀) - Alkylsulfonamido, N - ((C₁-C₁₀) alkyl) - (C₁- C₁₀) alkylsulfonamido, (C₇-C₁₆) aralkylsulfonamido, N - ((C₁-C₁₀) alkyl- (C₇-C₁₆) aralkylsulfonamido, where the radicals which contain an aryl radical in turn can be substituted on the aryl by 1 to 5 identical or different radicals from the series:
Hydroxy, halogen, cyano, trifluoromethyl, nitro, carboxy, (C₁-C₁₂) alkyl, (C₃-C₈) cycloalkyl, (C₆-C₁₂) aryl, (C₇-C₁₆) aralkyl, (C₁ -C₁₂) - Alkoxy, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxy, (C₆-C₁₂) aryloxy, (C₇-C₁₆) aralkyloxy, (C₁ -C₈) - hydroxyalkoyl,
(C₁-C₁₂) alkylcarbonyl, (C₃-C₈) cycloalkylcarbonyl, (C₆-C₁₂) arylcarbonyl, (C₇-C₁₆) aralkylcarbonyl,
(C₁-C₁₂) alkoxycarbonyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyl, (C₆-C₁₂) aryloxycarbonyl, (C₇-C₁₆) aralkoxycarbonyl, (C₃-C₈) - cycloalkoxycarbonyl, (C₂ -C₁₂) alkenyloxycarbonyl, (C₂-C₁₂) alkynyloxycarbonyl,
(C₁-C₁₂) alkylcarbonyloxy, (C₃-C₈) cycloalkylcarbonyloxy, (C₆-C₁₂) arylcarbonyloxy, (C₇-C₁₆) aralkylcarbonyloxy, cinnamoyloxy, (C₂-C₁₂) alkenylcarbonyloxy, (C₂-C₁₂), alkynylcarbonyloxy
(C₁-C₁₂) alkoxycarbonyloxy, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyloxy, (C₆-C₁₂) aryloxycarbonyloxy, (C₇-C₁₆) aralkyloxycarbonyloxy, (C₃-C₈) cycloalkoxycarbonyloxy, (C₂ -C₁₂) - alkenyloxycarbonyloxy, (C₂-C₁₂) alkynyloxycarbonyloxy,
Carbamoyl, N- (C₁-C₁₂) alkylcarbamoyl, N, N-di- (C₁-C₁₂) alkylcarbamoyl, N- (C₃-C₈) -cycloalkylcarbamoyl, N, N-dicyclo (C₃-C₈) -alkylcarbamoyl, N - (C₁-C₁₀) alkyl-N- (C₃-C₈) - cycloalkylcarbamoyl, N - ((C₃-C₈) cycloalkyl- (C₁-C₆) - alkyl) carbamoyl, N- (C₁-C₆) alkyl- N - ((C₃-C₈-cycloalkyl- (C₁-C₆) - alkyl) carbamoyl, N - (+) - dehydroabietylcarbamoyl, N- (C₁-C₆) alkyl- N-dehydroabietylcarbamoyl, N- (C₆-C₁₂) - Arylcarbamoyl, N- (C₇-C₁₆) aralkylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₆) arylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₇-C₁₆) aralkylcarbamoyl , N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N - ((C₆-C₁₆) aryloxy- (C₁- C₁₀) alkyl) carbamoyl, N - ((C₇-C₁₆) - Aralkyloxy- (C₁- C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₁-C₁₀) alkoxy- (C₁- C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl -N - ((C₆-C₁₂) aryloxy- (C₁- C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₇-C₁₆) aralkyloxy- (C - C₁₀) -alkyl) carbamoyl, CON (CH₂) h wherein a CH₂ group replaced by O, S, N- (C₁-C₈) alkylimino, N- (C₃-C₈) -Cycloalkylimino, N- (C₃-C₈) - cycloalkyl - (C₁-C₄) alkylimino, N- (C₆-C₁₂) arylimino, N- (C₇-C₁₆) aralkylimino or N- (C₁-C₄) alkoxy- (C₁-C₆) alkylimino can be replaced and h 3 to 7 means
Carbamoyloxy, N- (C₁-C₁₂) alkylcarbamoyloxy, N, N-Di- (C₁-C₁₂) alkylcarbamoyloxy, N- (C₃-C₈) cycloalkylcarbamoyloxy, N- (C₆-C₁₆) arylcarbamoyloxy, N- (C₇ -C₁₆) aralkylcarbamoyloxy, N- (C₁-C₁₀) - alkyl-N- (C₆-C₁₂) arylcarbamoyloxy, N- (C₁-C₁₀) alkyl-N- (C₇-C₁₆) - aralkylcarbamoyloxy, N - ((C₁ -C₁₀) alkyl)) carbamoyloxy, N - ((C₆-C₁₂) aryloxy- (C₁-C₁₀) alkyl) carbamoyloxy, N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₂) aryloxy- ( C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyloxy,
Amino, (C₁-C₁₂) alkylamino, di- (C₁-C₁₂) alkylamino, (C₃-C₈) cycloalkylamino, (C₃-C₁₂) alkenylamino, (C₃-C₁₂) alkynylamino, N- (C₆-C₁₂) -Arylamino, N- (C₇-C₁₁) aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C₁-C₁₂) alkoxyamino, (C₁-C₁₂) - alkoxy-N- (C₁-C₁₀) alkylamino ,
(C₁-C₁₂) alkanoylamino, (C₃-C₈) cycloalkanoylamino, (C₆-C₁₂) aroylamino, (C₇-C₁₆) aralkanoylamino, (C₁-C₁₂) alkanoyl-N- (C₁-C₁₀) alkylamino, (C₃-C₈) cycloalkanoyl-N- (C₁-C₁₀) alkylamino, (C₆-C₁₂) aroyl-N- (C₁-C₁₀) alkylamino, (C₇-C₁₁) - aralkanoyl-N- (C₁-C₁₀) -alkylamino,
(C₁-C₁₂) alkanoylamino- (C₁-C₈) alkyl, (C₃-C₈) -cycloalkanoylamino- (C₁-C₈) alkyl, (C₆-C₁₂) aroylamino- (C₁-C₈) alkyl, (C₇- C₁₆) aralkanoylamino (C₁-C₈) alkyl, amino- (C₁-C₁₀) alkyl, N- (C₁-C₁₀) alkylamino- (C₁-C₁₀) alkyl, N, N-di- (C₁-C₁₀) alkylamino (C₁-C₁₀) alkyl, (C₃-C₈) cycloalkylamino (C₁- C₁₀) alkyl,
(C₁-C₁₂) alkylmercapto, (C₁-C₁₂) alkylsulfinyl, (C₁-C₁₂) alkylsulfonyl, (C₆-C₁₆) arylmercapto, (C₆-C₁₆) arylsulfinyl, (C₆- C₁₆) arylsulfonyl, (C₇ -C₁₆) aralkylmercapto, (C₇-C₁₆) aralkylsulfinyl, (C₇-C₁₆) aralkylsulfonyl,
R¹ and R² or R² and R³ form a chain [CH₂] o in which one or two CH₂ groups of the saturated or unsaturated chain with a C = C double bond are optionally replaced by O, S, SO, SO₂ or NR ', o = 3, 4 or 5 and R ′ is hydrogen, (C₆-C₁₂) aryl, (C₁-C₈) alkyl, (C₁- C₈) alkoxy- (C₁-C₈) alkyl, (C₇-C₁₂) - Aralkoxy- (C₁-C₈) alkyl, (C₆-C₁₂) aryloxy- (C₁- C₈) alkyl, (C₁-C₁₀) alkanoyl, optionally substituted (C₇-C₁₆) aralkanoyl, optionally substituted (C₆- C₁₂) aroyl, or
form a carbocyclic or a heterocyclic 5- or 6-membered aromatic ring optionally substituted with fluorine, chlorine, (C₁-C₈) alkoxy or a carbamoyl radical,
R⁴ represents a branched or unbranched (C₁-C₂₀) alkyl radical or an aryl radical or a heteroaryl radical,
these radicals being substituted by one or more radicals from the series
(C₂-C₁₂) alkenyl, (C₂-C₁₂) alkynyl, (C₆-C₁₂) aryl, heteroaryl, (C₆-C₁₂) aralkyloxy, heteroalkyloxy, hydrogen, hydroxy, halogen, cyano, trifluoromethyl, nitro, carboxy, (C₁-C₁₂) alkyl, (C₃-C₈) cycloalkyl, (C₆-C₁₂) aryl, (C₇-C₁₆) aralkyl, (C₂-C₁₂) alkenyl, (C₂-C₁₂) alkynyl, (C₁ -C₁₂) alkoxy, (C₃-C₈) - cycloalkoxy, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxy, (C₆-C₁₂) - Aryloxy, (C₇-C₁₆) aralkyloxy, (C₆-C₁₂) aryloxy- (C₁-C₆) alkoxy, (C₇- C₁₆) aralkoxy- (C₁-C₆) alkoxy, -O- [CH 2- ] x C f H (2f + 1-g) F g , -OCF₂Cl, -OCF₂-CHFCl,
(C₁-C₁₂) alkylcarbonyl, (C₃-C₈) cycloalkylcarbonyl, (C₆-C₁₂) arylcarbonyl, (C₇-C₁₆) aralkylcarbonyl, cinnamoy, (C₂-C₁₂) alkenylcarbonyl, (C₂-C₁₂) alkynylcarbonyl,
(C₁-C₁₂) alkoxycarbonyl, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyl, (C₆-C₁₂) aryloxycarbonyl, (C₇-C₁₆) aralkoxycarbonyl, (C₃-C₈) cycloalkoxycarbonyl, (C₂ - C₁₂) alkenyloxycarbonyl, (C₂-C₁₂) alkynyloxycarbonyl,
(C₁-C₁₂) alkylcarbonyloxy, (C₃-C₈) cycloalkylcarbonyloxy, (C₆-C₁₂) arylcarbonyloxy, (C₇-C₁₆) aralkylcarbonyloxy, cinnamoyloxy, (C₂- C₁₂) alkenylcarbonyloxy, (C₂-C₁₂), alkynylcarbonyloxy
(C₁-C₁₂) alkoxycarbonyloxy, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkoxycarbonyloxy, (C₆-C₁₂) aryloxycarbonyloxy, (C₇-C₁₆) aralkyloxycarbonyloxy, (C₂-C₈) - cycloalkoxycarbonyloxy, (C₂ -C₁₂) alkenyloxycarbonyloxy, (C₂-C₁₂) alkynyloxycarbonyloxy,
Carbamoyl, N- (C₁-C₁₂) alkylcarbamoyl, N, N-di- (C₁-C₁₂) alkylcarbamoyl, N- (C₃-C₈) cycloalkylcarbamoyl, N, N-dicyclo (C₃-C₈) alkylcarbamoyl, N - (C₁-C₁₀) - alkyl-N- (C₃-C₈) -cycloalkylcarbamoyl, N- (C₃-C₈) -cycloalkyl- (C₁-C₆) - alkyl) carbamoyl, N- (C₁-C₆) -alkyl-N - ((C₃-C₈-Cycloalkyl- (C₁-C₆) -alkyl) carbamoyl, N - (+) - dehydroabietylcarbamoyl, N- (C₁-C₆) alkyl-N-dehydroabietylcarbamoyl, N- (C₆-C₁₂) arylcarbamoyl , N- (C₇-C₁₆) aralkylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₆- C₁₆) arylcarbamoyl, N- (C₁-C₁₀) alkyl-N- (C₇-C₁₆) aralkylcarbamoyl, N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N - ((C₆-C₁₆) aryloxy- (C₁-C₁₀) alkyl) carbamoyl, N - ((C₇-C₁₆) aralkyloxy - (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((- C₁-C₁₀) - alkoxy- (C₁-C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl -N - ((C₆-C₁₂) aryloxy- (C₁- C₁₀) alkyl) carbamoyl, N- (C₁-C₁₀) alkyl-N - ((C₇-C₁₆) aralkyloxy- (C₁- C ₀) alkyl) carbamoyl, CON (CH₂) h, in which a CH₂ group replaced by O, S, N- (C₁- C₈) alkylimino, N- (C₃-C₈) -Cycloalkylimino, N- (C₃-C₈) cycloalkyl - (C₁- C₄) alkylimino, N- (C₆-C₁₂) arylimino, N- (C₇-C₁₆) aralkylimino or N- (C₁-C₄) - alkoxy- (C₁-C₆) alkylimino can be replaced and h 3 to 7 means carbamoyloxy, N- (C₁-C₁₂) alkylcarbamoyloxy, N, N-di- (C₁-C₁₂) alkylcarbamoyloxy, N- (CÄC₈) cycloalkylcarbamoyloxy, N- (C₆-C₁₂) arylcarbamoyloxy, N- (C₇-C₁₆) aralkylcarbamoyloxy, N- (C₁-C₁₀) alkyl-N- (C₆- C₁₂) arylcarbamoyloxy, N- (C₁-C₁₀) alkyl-N- (C₇-C₁₆) aralkylcarbamoyloxy, N - ((C₁-C₁₀) alkyl) carbamoyloxy, N - ((C₆-C₁₂) aryloxy- (C₁- C₁₀) alkyl) carbamoyloxy, N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyloxy , N- (C₁-C₁₀) alkyl-N - ((C₁-C₁₀) alkoxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl-N - ((C₆-C₁₆) - Aryloxy- (C₁-C₁₀) alkyl) carbamoyloxy, N- (C₁-C₁₀) alkyl -N - ((C₇-C₁₆) aralkyloxy- (C₁-C₁₀) alkyl) carbamoyloxy,
Amino, (C₁-C₁₂) alkylamino, di- (C₁-C₁₂) alkylamino, (C₃-C₈) cycloalkylamino, (C₃-C₁₂) alkenylamino, (C₃-C₁₂) alkynylamino, N- (C₆-C₁₂) -Arylamino, N- (C₇- C₁₁) aralkylamino, N-alkyl-aralkylamino, N-alkyl-arylamino, (C₁-C₁₂) alkoxyamino, (C₁-C₁₂) alkoxy-N- (C₁-C₁₀) alkylamino ,
(C₁-C₁₂) alkanoylamino, (C₃-C₈) cycloalkanoylamino, (C₆-C₁₂) aroylamino, (C₇-C₁₆) aralkanoylamino, (C₁-C₁₂) alkanoyl-N- (C₁-C₁₀) alkylamino, (C₃-C₈) - cycloalkanoyl-N- (C₁-C₁₀) alkylamino, (C₆-C₁₂) aroyl-N- (C₁-C₁₀) alkylamino, (C₇- C₁₁) aralkanoyl-N- (C₁-C₁₀) -alkylamino,
(C₁-C₁₂) alkanoylamino- (C₁-C₈) alkyl, (C₃-C₈) cycloalkanoylamino- (C₁-C₈) alkyl, (C₆-C₁₆) aroylamino- (C₁-C₈) alkyl, (C₇- C₁₆) aralkanoylamino- (C₁-C₈) alkyl, amino- (C₁-C₁₀) alkyl, N- (C₁-C₁₀) alkylamino- (C₁-C₁₀) alkyl, N, N-di- (C₁- C₁₀) alkylamino (C₁-C₁₀) alkyl, (C₃-C₈) cycloalkylamino- (C₁-C₁₀) alkyl,
(C₁-C₁₂) alkylmercapto, (C₁-C₁₂) alkylsulfinyl, (C₁-C₁₂) alkylsulfonyl, (C₆-C₁₂) arylmercapto, (C₆-C₁₆) arylsulfinyl, (C₆-C₁₆) arylsulfonyl -C₁₆) - aralkylmercapto, (C₇-C₁₆) aralkylsulfinyl, (C₇-C₁₆) aralkylsulfonyl, sulfamoyl, N- (C₁-C₁₀) alkylsulfamoyl, N, N-di- (C₁-C₁₀) alkylsulfamoyl, (C₃ -C₈) - Cycloalkylsulfamoyl, N- (C₆- (C₁₂) arylsulfamoyl, N- (C₇-C₁₆) aralkylsulfamoyl, N- (C₁-C₁₀) alkyl-N- (C₆-C₁₂) arylsulfamoyl, N- ( C₁-C₁₀) alkyl-N- (C₇-C₁₆) aralkylsulfamoyl, (C₁-C₁₀) alkylsulfonamido, N - ((C₁-C₁₀) alkyl) - (C₁- C₁₀) alkylsulfonamido, (C₇-C₁₆) Aralkylsulfonamido, N - ((C₁-C₁₀) alkyl- (C₇-C₁₆) aralkylsulfonamido,
where the radicals which contain an aryl radical in turn can be substituted on the aryl by 1 to 5 identical or different radicals from the series: hydroxy, halogen, cyano, trifluoromethyl, nitro, carboxy, (C₁-C₁₂) alkyl, (C₃-C₈ ) -Cycloalkyl, (C₆-C₁₂) aryl, (C₇-C₁₆) aralkyl, (C₁-C₁₂) alkoxy, (C₁-C₁₂) alkoxy- (C₁-C₁₂) alkyl, (C₁-C₁₂) alkoxy - (C₁-C₁₂) alkoxy, (C₆-C₁₂) aryloxy, (C₇-C₁₆) aralkyloxy, (C₁-C₈) hydroxyalkoxy,
(C₁-C₁₂) alkylcarbonyl, (C₃-C₈) cycloalkylcarbonyl, (C₆-C₁₂) arylcarbonyl, (C₇- C₁₆) aralkylcarbonyl and,
if Q is NR ′, then R⁴ has the meaning of R ′ ′, where R ′ and R ′ ′ are the same or different and are hydrogen, (C₆-C₁₂) aryl, (C₁-C₈) alkyl, (C₁- C₈) alkoxy- (C₁-C₈) alkyl, (C₇-C₁₂) aralkoxy- (C₁-C₈) alkyl, (C₆-C₁₂) - aryloxy- (C₁-C₈) alkyl, (C₁-C₁₀) alkanoyl , optionally substituted (C₇-C₁₆) aralkanoyl, optionally substituted (C₆-C₁₂) aryl, or
R ′ and R ′ ′ together represent - [CH₂] h , in which a CH₂ group can be replaced by O, S, N-acylimino or N- (C₁-C₁₀) alkoxycarbonylimino, andf = 1 to 8,
g = 0.1 to (2f + 1),
x = 0 to 3,
h = 3 to 6 mean including the physiologically active salts, with the exception of 3-benzyloxypyridine-2-carboxylic acid L-threonylamide and 3-benzyloxypyridine-2-carboxylic acid - ((Fmoc-Phg) L-threonyl) amide hydrochloride. 2. Verbindungen der Formel I gemäß Anspruch 1, in der
Q = O,
X = O,
Y = CR³ oder, falls R¹ und R² einen Cyclus bilden, Y = N,
m = O,
A (C₁-C₃)-Alkylen, das gegebenenfalls einfach substituiert ist mit Halogen, Cyano, Trifluormethyl, (C₁-C₆)-Alkyl, (C₁-C₆)-Hydroxyalkyl, (C₁-C₆)- Alkoxy, -O-[CH₂]x-CfH(2f+i-g)Fg oder
A -CHR⁵- bedeutet, wobei R⁵ einen der Substituenten des α-C-Atoms einer α-Aminosäure bedeutet, insbesondere einer natürlichen L-Aminosäure und ihres D-Isomeren,
B CO₂H
R² Wasserstoff, (C₁-C₁₀)-Alkyl, (C₁-C₁₀)-Alkoxy, Halogen, CN, Trifluormethyl, (C₁-C₈)-Hydroxyalkyl, (C₁-C₁₀)-Alkoxycarbonyl, (C₃-C₁₀)- Cycloalkoxycarbonyl, (C₁-C₁₀)-Alkanoyl, (C₇-C₁₂)-Aralkanoyl, (C₆-C₁₂)- Aroyl,-O-[CH₂]xCfH(2f+1-g)Fg, NR′R′′, (C₁-C₁₀)-Alkylmercapto, (C₁-C₁₀)- Alkylsulfinyl, (C₁-C₁₀)-Alkylsulfonyl, (C₆-C₁₂)-Arylmercapto, (C₆-C₁₂)- Arylsulfinyl), (C₆-C₁₂)-Arylsulfonyl, (C₇-C₁₂)-Aralkylmercapto, (C₇-C₁₂)- Aralkylsulfinyl, (C₇-C₁₂)-Aralkylsulfonyl, (C₆-C₁₂)-Aryloxy, (C₇-C₁₆)- Aralkyloxy, Carboxy,
Carbamoyl, N-(C₁-C₁₀)-Alkylcarbamoyl, N, N-Di-(C₁-C₁₀)-alkylcarbamoyl, N-(C₃-C₈)-Cycloalkyl, N-(C₃-C₈)-Cycloalkylcarbamoyl, (C₁-C₄)- alkylcarbamoxyl, N-(C₆-C₁₂)-Arylcarbamoyl, N-(C₇-C₁₆)-Aralkylcarbamoyl, N-(C₁-C₆)-Alkyl-N-(C₈-C₁₂)arylcarbamoyl, N-(C₁-C₆)-Alkyl-N-(C₇-C₁₆)- Aralkylcarbamoyl, N-((C₁-C₆)-Alkoxy- (C₁-C₆)alkyl)carbamoyl,
wobei Aryl in der Weise substiuiert ist wie für R¹ und R³ definiert,
R¹ und R³ gleich oder verschieden sind und Wasserstoff, Halogen, (C₁-C₁₂)- Alkyl, (C₁-C₁₂)-Alkoxy, -O-[CH₂]x-CfH(2f+1-g)Halg, (C₁-C₁₂)-Alkoxy- (C₁-C₁₂)-alkyl, (C₁-C₈)-Alkoxy-(C₁-C₁₂)-alkoxy, (C₁-C₁₂)-Alkoxy-(C₁-C₈)- alkoxy-(C₂-C₆)-alkyl, (C₇-C₁₁)-Aralkyloxy, (C₃-C₈)-Cycloalkyl, (C₃-C₈)- Cycloalkyl-(C₁-C₈)-alkyl, (C₃-C₈)-Cycloalkyloxy, (C₃-C₈)-Cycloalkyl-(C₁- C₈)-alkoxy, (C₃-C₈)-Cycloalkyloxy-(C₁-C₈)-alkyl, (C₃-C₈)-Cycloalkyloxy- (C₁-C₈)-alkoxy, (C₃-C₈)-Cycloalkyl-(C₁-C₆)-alkyl-(C₁-C₆)-alkoxy, (C₃-C₈)- Cycloalkyl-(C₁-C₆)-alkoxy-(C₁-C₆)-alkyl, (C₃-C₈)-Cycloalkoxy-(C₁-C₆)- alkoxy-(C₁-C₆)-alkyl, NR′R′′, (C₁-C₈)-Alkylmercapto, (C₁-C₈)-Alkylsulfinyl oder (C₁-C₈)-Alkylsulfonyl, (C₆-C₁₂)-Arylmercapto, (C₆-C₁₂)-Arylsulfinyl, (C₆-C₁₂)-Arylsulfonyl, (C₇-C₁₂)-Aralkylmercapto, (C₇-C₁₁)-Aralkylsulfinyl, (C₇-C₁₁)-Aralkylsulfonyl, substituiertes (C₆-C₁₂)-Aryloxy-(C₁-C₆)-alkyl, (C₇-C₁₁)-Aralkoxy-(C₁-C₆)-alkyl, (C₆-C₁₂)-Aryloxy-(C₁-C₆)-alkoxy-(C₁-C₆)- alkyl, (C₇-C₁₁)-Aralkyloxy-(C₁-C₆)-alkoxy-(C₁-C₆)alkyl, (C₆-C₁₂)-Aryloxy, (C₇-C₁₁)-Aralkyloxy, (C₆-C₁₂)-Aryloxy-(C₁-C₆)-alkoxy oder (C₇-C₁₁)- Aralkoxy-(C₁-C₆)-alkoxy bedeutet, wobei ein aromatischer Rest mit 1, 2, 3, 4 oder 5 gleichen oder verschiedenen Substituenten aus der Reihe Wasserstoff, Halogen, Cyano, Nitro, Trifluormethyl, (C₁-C₆)-Alkyl, (C₁- C₆)-Hydroxyalkyl, (C₁-C₆)-Alkoxy, -O-[CH₂]xCfH(2f+1-g)Fg, -OCF₂Cl, -O-CF₂-CHFCl, (C₁-C₆)-Alkylmercapto, (C₁-C₆)-Alkylsulfinyl, (C₁ -C₆)- Alkylsulfonyl, (C₁-C₆)-Alkylcarbonyl, (C₁-C₆)-Alkoxycarbonyl, Carbamoyl, N-(C₁-C₄)-Alkylcarbamoyl, N,N-Di-(C₁-C₄) alkylcarbamoyl, (C₁-C₆) Alkylcarbonyloxy, (C₃-C₈)-Cycloalkylcarbamoyl, Phenyl, Benzyl, Phenoxy, Benzyloxy, NR′ R′′′, Phenylmercapto, Phenylsulfonyl, Phenylsulfinyl, Sulfamoyl, N-(C₁-C₄)-Alkylsulfamoyl oder N,N-Di-(C₁-C₄)-alkylsulfamoyl trägt, oder gegebenenfalls bis zu 3 der vorstehend genannten gleichen oder verschiedenen Substituenten trägt und zwei benachbarte C-Atome des Aralkyloxyrestes gemeinsam eine Kette -[CH₂-] und/oder -CH = CH- CH = CH- tragen, wobei eine CH₂-Gruppe der Kette gegebenenfalls durch O, S, SO, SO₂ oder NR′ ersetzt ist, oder
R¹ und R² oder R² und R³ eine Kette [CH₂]o bilden, wobei o = 3, 4 oder 5 bedeutet, oder
einen, gegebenenfalls mit Fluor, Chlor (C₁-C₈)-Alkoxy oder einem Carbamoyl- Rest substituierten, carbocyclischen 6gliedrigen aromatischen Ring bilden,
R⁴ einen verzweigten oder unverzweigten (C₁-C₂₀)-Alkylrest, der bis zu 3 C- C-Mehrfachbindungen enthalten kann, (C₁-C₁₂)-Alkoxy-(C₁-C₈)-alkyl, (C₁- C₁₂)-Alkoxy-(C₁-C₈)-alkoxy-(C₁-C₈)-alkyl, [CH₂]x CfH(2f+1-g)Fg, oder (C₆- C₁₂)-Aryl, (C₇-C₁₁)-Aralkyl, Heteroaryl, Heteroaralkyl, (C₃-C₈)-Cycloalkyl, (C₃-C₈)-Cycloalkyl-(C₁-C₆)-alkyl, (C₆-C₁₄)-Aryloxy-(C₁-C₈)-alkyl, Heteroaryloxy-(C₁-C₈)-alkyl, (C₃-C₈)-Cycloalkyloxy-(C₁-C₈)-alkyl, (C₇-C₁₆)- Aralkyloxy-(C₁-C₈)-alkyl, Heteroaralkyloxy-(C₁-C₈)-alkyl,
(C₆-C₁₄)-Aryloxy-(C₁-C₈)-alkoxy-(C₁-C₈)-alkyl, Heteroalkyl-(C₁-C₈)-alkoxy-(C₁-C₈)-alkyl, (C₃-C₈)-Cycloalkoxy-(C₁-C₈)- alkoxy-(C₁-C₆)-alkyl,
(C₇-C₁₆)-Aralkyloxy-(C₁-C₈)-alkoxy-(C₁-C₈)alkyl, Heteroaralkyloxy-(C₁-C₈)-alkoxy-(C₁-C₈)-alkyl, (C₃-C₈)-Cycloalkyl-(C₁-C₆)- alkoxy-(C₁-C₆)-alkyl oder
einen Rest der Formel Z, [CH₂]v-[O]w-[CH₂]t-E (Z),worin E einen substituierten Phenylrest der Formel F oder einen substituierten Heteroaryl-Rest, oder einen substituierten (C₃-C₈)- Cycloalkylrest, wobei
v = 0, 1, 2, 3, 4, 5, 6 w = 0,1 und t = 0, 1, 2, 3, mit der Einschränkung, daß v ungleich 0 ist, falls w = 1 ist bedeutet und R⁶, R⁷, R⁸, R⁹ und R¹⁰ gleich oder verschieden sind und Wasserstoff, Halogen, Cyano, Nitro, Trifluormethyl, (C₁-C₆)-Alkyl, (C₃-C₈-Cycloalkyl, (C₁-C₆)-Alkoxy, -O-[CH2-]xCfH(2f+1-g)Fg, -OCF₂Cl, -O-CF₂-CHFCl, (C₁-C₆)- Alkylmercapto, (C₁-C₆)-Hydroxyalkyl, (C₁-C₆)-Alkoxy-(C₁-C₆)-alkoxy, (C₁-C₆)-Alkoxy-(C₁-C₆)-alkyl, (C₁-C₆)-Alkylsulfinyl, (C₁-C₆)-Alkylsulfonyl, (C₁-C₆)-Alkylcarbonyl, (C₁-C₈)-Alkoxycarbonyl, Carbamoyl, N-(C₁-C₈)- Alkylcarbamoyl, N,N-Di-(C₁-C₈)-alkylcarbamoyl, gegebenenfalls mit Fluor, Chlor, Brom, Trifluormethyl und (C₁-C₆)-Alkoxy-substituiertes (C₇-C₁₁)- Aralkylcarbamoyl, N-(C₃-C₈)-Cycloalkylcarbamoyl, N-(C₃-C₈)-Cycloalkyl- (C₁-C₄)-alkylcarbamoyl, (C₁-C₆)-Alkylcarbonyloxy, Phenyl, Benzyl, Phenoxy, Benzyloxy, NR′R′′, wie Amino, Anilino, N-Methylanilino, Phenylmercapto, Phenylsulfonyl, Phenylsulfinyl, Sulfamoyl, N-(C₁-C₈)- Alkylsulfamoyl oder N,N-Di-(C₁-C₈)-alkylsulfamoyl bedeuten, oder zwei benachbarte Substituenten gemeinsam eine Kette -[CH2-]n oder -CH=CH- CH=CH- bedeuten, wobei eine CH₂-Gruppe der Kette gegebenenfalls durch O, S, SO, SO₂ oder NR′ ersetzt ist,
R′ und R′′ gleich oder verschieden sind und Wasserstoff, (C₆-C₁₂)-Aryl, (C₁-C₁₀)-Alkyl, (C₃-C₁₀)-Cycloalkyl, (C₁-C₈)-Alkoxy-(C₁-C₈)alkyl, (C₇-C₁₂)-Aralkoxy-(C₁-C₈)alkyl, (C₆-C₁₂)-Aryloxy-(C₁-C₈)-alkyl, (C₁-C₁₀)- Alkanoyl, ggf. substituiertes (C₇-C₁₆)-Aralkanoyl, ggf. substituiertes (C₆-C₁₂)-Aroyl, odergemeinsam für -[CH₂]h- stehen, worin eine CH₂-Gruppe durch O, S, N-(C₁-C₄)- Alkanoylimino oder N-(C₁-C₄)-Alkoxycarbonylimino ersetzt sein kann, undf = 1 bis 8,
g = 0, 1 bis (2f+1),
h = 3 bis 6 und
x = 0 bis 3 bedeuten,einschließlich der physiologisch wirksamen Salze, wobei B-Benzyloxypyridin-2- carbonsäure-L-threonylamid und 3-Benzyloxy-pyridin-2-carbonsäure-((Fmoc-Phg)- L-threonyl)amid-Hydrochlorid ausgenommen sind.2. Compounds of formula I according to claim 1, in which
Q = O,
X = O,
Y = CR³ or, if R¹ and R² form a cycle, Y = N,
m = O,
A (C₁-C₃) alkylene, which is optionally monosubstituted with halogen, cyano, trifluoromethyl, (C₁-C₆) alkyl, (C₁-C₆) hydroxyalkyl, (C₁-C₆) alkoxy, -O- [CH₂ ] x -C f H (2f + ig) F g or
A means -CHR⁵-, where R⁵ means one of the substituents of the α-C atom of an α-amino acid, in particular a natural L-amino acid and its D isomer,
B CO₂H
R² is hydrogen, (C₁-C₁₀) alkyl, (C₁-C₁₀) alkoxy, halogen, CN, trifluoromethyl, (C₁-C₈) hydroxyalkyl, (C₁-C₁₀) alkoxycarbonyl, (C₃-C₁₀) cycloalkoxycarbonyl, ( C₁-C₁₀) alkanoyl, (C₇-C₁₂) aralkanoyl, (C₆-C₁₂) aroyl, -O- [CH₂] x C f H (2f + 1-g) F g , NR′R ′ ′, ( C₁-C₁₀) alkylmercapto, (C₁-C₁₀) alkylsulfinyl, (C₁-C₁₀) alkylsulfonyl, (C₆-C₁₂) arylmercapto, (C₆-C₁₂) arylsulfinyl), (C₆-C₁₂) arylsulfonyl, (C₇ -C₁₂) aralkylmercapto, (C₇-C₁₂) aralkylsulfinyl, (C₇-C₁₂) aralkylsulfonyl, (C₆-C₁₂) aryloxy, (C₇-C₁₆) aralkyloxy, carboxy,
Carbamoyl, N- (C₁-C₁₀) alkylcarbamoyl, N, N-di- (C₁-C₁₀) alkylcarbamoyl, N- (C₃-C₈) cycloalkyl, N- (C₃-C₈) cycloalkylcarbamoyl, (C₁-C₄ ) - alkylcarbamoxyl, N- (C₆-C₁₂) arylcarbamoyl, N- (C₇-C₁₆) aralkylcarbamoyl, N- (C₁-C₆) alkyl-N- (C₈-C₁₂) arylcarbamoyl, N- (C₁-C₆) -Alkyl-N- (C₇-C₁₆) aralkylcarbamoyl, N - ((C₁-C₆) alkoxy- (C₁-C₆) alkyl) carbamoyl,
where aryl is substituted as defined for R¹ and R³,
R¹ and R³ are the same or different and are hydrogen, halogen, (C₁-C₁₂) alkyl, (C₁-C₁₂) alkoxy, -O- [CH₂] x -C f H (2f + 1-g) Hal g , ( C₁-C₁₂) alkoxy- (C₁-C₁₂) alkyl, (C₁-C₈) alkoxy- (C₁-C₁₂) alkoxy, (C₁-C₁₂) alkoxy- (C₁-C₈) - alkoxy- (C₂- C₆) alkyl, (C₇-C₁₁) aralkyloxy, (C₃-C₈) cycloalkyl, (C₃-C₈) - cycloalkyl- (C₁-C₈) alkyl, (C₃-C₈) cycloalkyloxy, (C₃-C₈) -Cycloalkyl- (C₁- C₈) alkoxy, (C₃-C₈) -cycloalkyloxy- (C₁-C₈) alkyl, (C₃-C₈) -cycloalkyloxy- (C₁-C₈) alkoxy, (C₃-C₈) cycloalkyl - (C₁-C₆) alkyl- (C₁-C₆) alkoxy, (C₃-C₈) - cycloalkyl- (C₁-C₆) alkoxy- (C₁-C₆) alkyl, (C₃-C₈) cycloalkoxy- ( C₁-C₆) - alkoxy- (C₁-C₆) alkyl, NR′R ′ ′, (C₁-C₈) alkylmercapto, (C₁-C₈) alkylsulfinyl or (C₁-C₈) alkylsulfonyl, (C₆-C₁₂) Arylmercapto, (C₆-C₁₂) arylsulfinyl, (C₆-C₁₂) arylsulfonyl, (C₇-C₁₂) aralkylmercapto, (C₇-C₁₁) aralkylsulfinyl, (C₇-C ₁) aralkylsulfonyl, substituted (C₆-C₁₂) aryloxy- (C₁-C₆) alkyl, (C₇-C₁₁) aralkoxy- (C₁-C₆) alkyl, (C₆-C₁₂) aryloxy- (C₁-C₆ ) -alkoxy- (C₁-C₆) alkyl, (C₇-C₁₁) aralkyloxy- (C₁-C₆) alkoxy- (C₁-C₆) alkyl, (C₆-C₁₂) aryloxy, (C₇-C₁₁) aralkyloxy , (C₆-C₁₂) aryloxy- (C₁-C₆) alkoxy or (C₇-C₁₁) - aralkoxy- (C₁-C₆) alkoxy, an aromatic radical having 1, 2, 3, 4 or 5 being the same or various substituents from the series hydrogen, halogen, cyano, nitro, trifluoromethyl, (C₁-C₆) alkyl, (C₁- C₆) hydroxyalkyl, (C₁-C₆) alkoxy, -O- [CH₂] x C f H ( 2f + 1-g) F g , -OCF₂Cl, -O-CF₂-CHFCl, (C₁-C₆) alkylmercapto, (C₁-C₆) alkylsulfinyl, (C₁-C₆) alkylsulfonyl, (C₁-C₆) alkylcarbonyl , (C₁-C₆) alkoxycarbonyl, carbamoyl, N- (C₁-C₄) alkylcarbamoyl, N, N-di- (C₁-C₄) alkylcarbamoyl, (C₁-C₆) alkylcarbonyloxy, (C₃-C₈) cycloalkylcarbamoyl, phenyl , Benzyl, phenoxy, benzyloxy, NR 'R''', phenylmercapto, phenylsulfonyl, phenylsulfinyl, sulfamoyl, N- (C₁-C₄) alkylsulfamoyl or N, N-di- (C₁-C₄) alkylsulfamoyl, or optionally up to 3 of the same or different mentioned above Bears substituents and two adjacent C atoms of the aralkyloxy group together carry a chain - [CH₂-] and / or -CH = CH- CH = CH-, with a CH₂ group of the chain optionally by O, S, SO, SO₂ or NR 'Is replaced, or
R¹ and R² or R² and R³ form a chain [CH₂] o , where o = 3, 4 or 5, or
form a carbocyclic 6-membered aromatic ring optionally substituted with fluorine, chlorine (C₁-C₈) alkoxy or a carbamoyl radical,
R⁴ is a branched or unbranched (C₁-C₂₀) alkyl radical which can contain up to 3 C-C multiple bonds, (C₁-C₁₂) alkoxy- (C₁-C₈) alkyl, (C₁- C₁₂) alkoxy- ( C₁-C₈) alkoxy- (C₁-C₈) alkyl, [CH₂] x C f H (2f + 1-g) F g , or (C₆- C₁₂) aryl, (C₇-C₁₁) aralkyl, heteroaryl , Heteroaralkyl, (C₃-C₈) cycloalkyl, (C₃-C₈) cycloalkyl- (C₁-C₆) alkyl, (C₆-C₁₄) aryloxy- (C₁-C₈) alkyl, heteroaryloxy- (C₁-C₈) -alkyl, (C₃-C₈) -cycloalkyloxy- (C₁-C₈) -alkyl, (C₇-C₁₆) - aralkyloxy- (C₁-C₈) -alkyl, heteroaralkyloxy- (C₁-C₈) -alkyl,
(C₆-C₁₄) aryloxy- (C₁-C₈) alkoxy- (C₁-C₈) alkyl, heteroalkyl- (C₁-C₈) alkoxy- (C₁-C₈) alkyl, (C₃-C₈) cycloalkoxy- (C₁-C₈) - alkoxy- (C₁-C₆) alkyl,
(C₇-C₁₆) aralkyloxy- (C₁-C₈) alkoxy- (C₁-C₈) alkyl, heteroaralkyloxy- (C₁-C₈) alkoxy- (C₁-C₈) alkyl, (C₃-C₈) cycloalkyl- ( C₁-C₆) - alkoxy- (C₁-C₆) alkyl or
a radical of the formula Z, [CH₂] v - [O] w - [CH₂] t -E (Z), in which E is a substituted phenyl radical of the formula F. or a substituted heteroaryl radical, or a substituted (C₃-C₈) - cycloalkyl radical, where
v = 0, 1, 2, 3, 4, 5, 6 w = 0.1 and t = 0, 1, 2, 3, with the restriction that v is not equal to 0 if w = 1 and R⁶, R⁷, R⁸, R⁹ and R¹⁰ are the same or different and are hydrogen, halogen, cyano, nitro, trifluoromethyl, (C₁-C₆) alkyl, (C₃-C₈-cycloalkyl, (C₁-C₆) alkoxy, -O- [CH 2- ] x C f H (2f + 1-g) F g , -OCF₂Cl, -O-CF₂-CHFCl, (C₁-C₆) alkylmercapto, (C₁-C₆) hydroxyalkyl, (C₁-C₆) alkoxy - (C₁-C₆) alkoxy, (C₁-C₆) alkoxy- (C₁-C₆) alkyl, (C₁-C₆) alkylsulfinyl, (C₁-C₆) alkylsulfonyl, (C₁-C₆) alkylcarbonyl, ( C₁-C₈) alkoxycarbonyl, carbamoyl, N- (C₁-C₈) alkylcarbamoyl, N, N-di- (C₁-C₈) alkylcarbamoyl, optionally with fluorine, chlorine, bromine, trifluoromethyl and (C₁-C₆) alkoxy -substituted (C₇-C₁₁) aralkylcarbamoyl, N- (C₃-C₈) cycloalkylcarbamoyl, N- (C₃-C₈) cycloalkyl- (C₁-C₄) alkylcarbamoyl, (C₁-C₆) alkylcarbonyloxy, phenyl, benzyl, Phenoxy, benzyloxy, NR'R '', such as amino, aniline o, N-methylanilino, phenylmercapto, phenylsulfonyl, phenylsulfinyl, sulfamoyl, N- (C₁-C₈) -alkylsulfamoyl or N, N-di- (C₁-C₈) -alkylsulfamoyl, or two adjacent substituents together represent a chain - [CH 2 - ] n or -CH = CH- CH = CH-, where a CH₂ group of the chain is optionally replaced by O, S, SO, SO₂ or NR ',
R ′ and R ′ ′ are identical or different and are hydrogen, (C₆-C₁₂) aryl, (C₁-C₁₀) alkyl, (C₃-C₁₀) cycloalkyl, (C₁-C₈) alkoxy- (C₁-C₈) alkyl, (C₇-C₁₂) aralkoxy- (C₁-C₈) alkyl, (C₆-C₁₂) aryloxy- (C₁-C₈) alkyl, (C₁-C₁₀) alkanoyl, optionally substituted (C₇-C₁₆) - Aralkanoyl, optionally substituted (C₆-C₁₂) aroyl, or together represent - [CH₂] h -, in which a CH₂ group is represented by O, S, N- (C₁-C₄) alkanoylimino or N- (C₁-C₄) Alkoxycarbonylimino can be replaced, andf = 1 to 8,
g = 0.1 to (2f + 1),
h = 3 to 6 and
x = 0 to 3, including the physiologically active salts, where B-benzyloxypyridine-2-carboxylic acid L-threonylamide and 3-benzyloxypyridine-2-carboxylic acid - ((Fmoc-Phg) - L-threonyl) amide hydrochloride with exception of. 3. Verbindungen der Formel I gemäß den Ansprüchen 1 oder 2, in der
Q = O,
X = O,
Y = CR³ oder Y = N, falls R¹ und R² mit dem sie tragenden Ring einen Cinnolin-Ring bilden,
m = O,
A -CHR⁵-, wobei R⁵ den Substituenten des α-C-Atoms einer α-Aminosäure bedeutet, insbesondere einer natürlichen L-Aminosäure oder ihr D- lsomeres,
B = CO₂H,
R² Wasserstoff, Chlor, (C₁-C₈)-Alkoxy, Carbamoyl, N-(C₁-C₁₀)-Alkylcarbamoyl, N,N-Di-(C₁-C₈)-alkylcarbamoyl, N-(C₃-C₈)-Cycloalkylcarbamoyl, N-(C₆-C₁₂)-Phenylcarbamoyl, N-(C₇-C₁₂)- Phenylalkylcarbamoyl, N-(C₁-C₆)-Alkyl-N-(C₆-C₁₂)phenylcarbamoyl, N-(C₁-C₆)-Alkyl-(C₇-C₁₂)-Phenylalkylcarbamoyl, N-((C₁-C₆)-Alkoxy- (C₁-C₆)alkyl)carbamoyl, (C₁-C₈)-Alkoxycarbonyl, (C₃-C₈)- Cycloalkoxycarbonyl, wobei ein Phenylrest in der Weise substituiert ist wie für R¹ und R³ definiert, und einer der Reste
R¹ und R³ Wasserstoff und der andere einen Rest aus der Reihe Wasserstoff, Fluor, Chlor, (C₁-C₈)-Alkyl, (C₁-C₁₀)-Alkoxy, (C₅-C₆)-Cycloalkyl, (C₅-C₆)-Cycloalkyl-(C₁-C₆)-alkyl, (C₅-C₆)-Cycloalkyloxy, (C₅-C₆)- Cycloalkyl-(C₁-C₆)-alkoxy, (C₅-C₆)-Cycloalkyloxy-(C₁-C₆)-alkyl, (C₅- C₆)-Cycloalkyloxy-(C₁-C₆)-alkoxy, (C₅-C₆)-Cycloalkyl-(C₁-C₄)-alkyl- (C₁-C₄)-alkoxy, (C₅-C₆)-Cycloalkyl-(C₁-C₄)-alkoxy-(C₁-C₂)-alkyl, (C₅-C₆)-Cycloalkoxy-(C₁-C₄)-alkoxy-(C₁-C₂)-alkyl, -O-[CH₂]x- CfH(2f+1-g)Fg, -NR′R′′, (C₁-C₆)-Alkoxy-(C₁-C₆)-alkyl, (C₁-C₆)- Alkoxy-(C₁-C₆)-alkoxy, (C₁-C₆)-Alkoxy-(C₁-C₄)-alkoxy-(C₁-C₂)-alkyl, substituiertes (C₆-C₁₂)-Phenoxy, (C₇-C₁₁)-Phenylalkyloxy, (C₆-C₁₂)- Phenoxy-(C₁-C₆)-alkoxy oder (C₇-C₁₁)-Phenylalkoxy-(C₁-C₆)-alkoxy, Phenoxy-(C₁-C₄)-alkyl, (C₇-C₁₁)-Phenyl(alkyloxy-(C₁-C₄)-alkyl, Phenoxy-(C₁-C₄)-alkoxy-(C₁-C₂)-alkyl, (C₇-C₁₁)-Phenylalkyloxy- (C₁-C₄)-alkoxy-(C₁-C₂)-alkyl bedeutet, wobei ein aromatischer Rest mit 1, 2 oder 3 gleichen oder verschiedenen Substituenten aus der Reihe Fluor, Chlor, Brom, Cyano, Trifluormethyl, (C₁-C₆)-Alkyl, (C₁-C₆)-Alkoxy, substituiert ist, oder
R¹ und R² mit dem sie tragenden Pyridin einen 5,6,7,8-Tetrahydroisochinolin- Ring, oder
einen, gegebenenfalls substituierten, carbocyclischen 6gliedrigen aromatischen Ring bilden, wobei R¹ und R² mit dem sie tragenden Pyridin bzw. Pyridazin für ein Isochinolin- bzw. einen Cinnolin-Ring stehen,
R⁴ einen verzweigten oder unverzweigten (C₁-C₂₀)-Alkylrest, der eine oder zwei C-C-Mehrfachbindungen enthalten kann, oder
(C₁-C₈)-Alkoxy-(C₁-C₆)-alkyl, (C₁-C₆)-Alkoxy-(C₁-C₄)-alkoxy-(C₁-C₄)alkyl
oder einen Rest der Formel Z bedeutet,
[CH₂]v-[O]w-[CH₂]t-E (Z),
wobei E einen substituierten Phenylrest der Formel F oder einen (C₃-C₈)-Cycloalkylrest bedeutet, wobei v = 0, 1, 2, 3, w = 0, 1 und t = 0, 1 sein kann, mit der Einschränkung, daß v ungleich 0 ist, falls w = 1 ist, und worin R⁶, R⁷, R⁸, R⁹ und R¹⁰ gleich oder verschieden sind und Wasserstoff, Fluor, Chlor, Cyano, Trifluormethyl, (C₁-C₆)-Alkyl, (C₁-C₆)- Alkoxy, -O-[CH2-]xCfH(2f+1-g)Fg, N-(C₁-C₈)-Alkylcarbamoyl, N,N-Di-(C₁- C₈)-alkylcarbamoyl, N-(C₃-C₈)-Cycloalkylcarbamoyl, gegebenenfalls mit Fluor, Chlor, Trifluormethyl und (C₁-C₆)-Alkoxy substituiertes (C₇-C₁₁)- Phenylalkylcarbamoyl bedeuten.3. Compounds of formula I according to claims 1 or 2, in which
Q = O,
X = O,
Y = CR³ or Y = N, if R¹ and R² form a cinnolin ring with the ring carrying them,
m = O,
A -CHR⁵-, where R⁵ is the substituent of the α-C atom of an α-amino acid, in particular a natural L-amino acid or its D-isomer,
B = CO₂H,
R² is hydrogen, chlorine, (C₁-C₈) alkoxy, carbamoyl, N- (C₁-C₁₀) alkylcarbamoyl, N, N-di- (C₁-C₈) alkylcarbamoyl, N- (C₃-C₈) cycloalkylcarbamoyl, N - (C₆-C₁₂) phenylcarbamoyl, N- (C₇-C₁₂) - phenylalkylcarbamoyl, N- (C₁-C₆) alkyl-N- (C₆-C₁₂) phenylcarbamoyl, N- (C₁-C₆) alkyl- (C₇ -C₁₂) phenylalkylcarbamoyl, N - ((C₁-C₆) alkoxy- (C₁-C₆) alkyl) carbamoyl, (C₁-C₈) alkoxycarbonyl, (C₃-C₈) - cycloalkoxycarbonyl, a phenyl radical being substituted in the manner as defined for R¹ and R³, and one of the residues
R¹ and R³ are hydrogen and the other is a radical from the series consisting of hydrogen, fluorine, chlorine, (C₁-C₈) alkyl, (C₁-C₁₀) alkoxy, (C₅-C₆) cycloalkyl, (C₅-C₆) cycloalkyl- (C₁-C₆) alkyl, (C₅-C₆) cycloalkyloxy, (C₅-C₆) - cycloalkyl- (C₁-C₆) alkoxy, (C₅-C₆) cycloalkyloxy- (C₁-C₆) alkyl, (C₅ - C₆) Cycloalkyloxy- (C₁-C₆) alkoxy, (C₅-C₆) cycloalkyl- (C₁-C₄) alkyl- (C₁-C₄) alkoxy, (C₅-C₆) cycloalkyl- (C₁-C₄ ) -alkoxy- (C₁-C₂) -alkyl, (C₅-C₆) -cycloalkoxy- (C₁-C₄) -alkoxy- (C₁-C₂) -alkyl, -O- [CH₂] x - C f H (2f + 1-g) F g , -NR'R '', (C₁-C₆) alkoxy- (C₁-C₆) alkyl, (C₁-C₆) - alkoxy- (C₁-C₆) alkoxy, (C₁-C₆ ) Alkoxy- (C₁-C₄) alkoxy- (C₁-C₂) alkyl, substituted (C₆-C₁₂) phenoxy, (C₇-C₁₁) phenylalkyloxy, (C₆-C₁₂) - phenoxy- (C₁-C₆) -alkoxy or (C₇-C₁₁) -phenylalkoxy- (C₁-C₆) -alkoxy, phenoxy- (C₁-C₄) -alkyl, (C₇-C₁₁) -phenyl (alkyloxy- (C₁-C₄) -alkyl, phenoxy- ( C₁-C₄) alko xy- (C₁-C₂) alkyl, (C₇-C₁₁) -phenylalkyloxy- (C₁-C₄) -alkoxy- (C₁-C₂) -alkyl means, an aromatic radical having 1, 2 or 3 identical or different substituents the series fluorine, chlorine, bromine, cyano, trifluoromethyl, (C₁-C₆) alkyl, (C₁-C₆) alkoxy, is substituted, or
R¹ and R² with the pyridine carrying them a 5,6,7,8-tetrahydroisoquinoline ring, or
form an optionally substituted, carbocyclic 6-membered aromatic ring, R¹ and R² together with the pyridine or pyridazine carrying them being an isoquinoline or a cinnoline ring,
R⁴ is a branched or unbranched (C₁-C₂₀) alkyl radical which may contain one or two CC multiple bonds, or
(C₁-C₈) alkoxy- (C₁-C₆) alkyl, (C₁-C₆) alkoxy- (C₁-C₄) alkoxy- (C₁-C₄) alkyl
or represents a radical of the formula Z,
[CH₂] v - [O] w - [CH₂] t -E (Z),
where E is a substituted phenyl radical of the formula F or a (C₃-C₈) cycloalkyl radical, where v = 0, 1, 2, 3, w = 0, 1 and t = 0, 1, with the restriction that v is not equal to 0 if w = 1 is, and in which R⁶, R⁷, R⁸, R⁹ and R¹⁰ are identical or different and are hydrogen, fluorine, chlorine, cyano, trifluoromethyl, (C₁-C₆) alkyl, (C₁-C₆) alkoxy, -O- [CH 2 - ] x C f H (2f + 1-g) F g , N- (C₁-C₈) alkylcarbamoyl, N, N-di- (C₁- C₈) alkylcarbamoyl, N- (C₃-C₈) cycloalkylcarbamoyl, optionally substituted with fluorine, chlorine, trifluoromethyl and (C₁-C₆) alkoxy (C₇-C₁₁) - phenylalkylcarbamoyl. 4. Verbindungen der Formel I gemäß den Ansprüchen 1 bis 3 zuzüglich 3- Benzyloxy-pyridin-2-carbonsäure-L-threonylamid und 3-Benzyloxy-pyridin-2- carbonsäure-((Fmoc-Phg)-L-threonyl)amid zur Anwendung als Arzneimittel.4. Compounds of formula I according to claims 1 to 3 plus 3- Benzyloxy-pyridine-2-carboxylic acid-L-threonylamide and 3-benzyloxy-pyridine-2- carboxylic acid - ((Fmoc-Phg) -L-threonyl) amide for use as a medicine. 5. Verbindungen gemäß Anspruch 4 für die Anwendung zur Kollagenbiosynthese.5. Compounds according to claim 4 for use in Collagen biosynthesis. 6. Verbindungen gemäß Anspruch 4 zur Anwendung als Fibrosupressiva.6. Compounds according to claim 4 for use as fibrosupressives. 7. Verbindungen gemäß Anspruch 4 zur Herstellung einer Arzneimittels gegen fibrotische Erkrankungen.7. Compounds according to claim 4 for the manufacture of a medicament against fibrotic diseases. 8. Verfahren zur Herstellung von Verbindungen nach Formel I gemäß den Ansprüchen 1 bis 4, in der A einen substituierten Alkylen-Teil, B = CO₂H, Y = CR³ und m = 0 und 1 bedeuten, indem
  • i1.) Pyridin-2-carbonsäuren der Formel II (R¹¹ = H) mit den Aminoestern der Formel III zu den Amidestern der Formel IV umgesetzt werden, oder
  • i2.) Pyridin-2-carbonsäureester der Formel II (R¹¹=niedrig Alkyl) unter den Bedingungen der Aminolyse zu den Verbindungen der Formel IV umgesetzt werden; und
  • ii) die Verbindungen der Formel I aus ihren Estern der Formel IV freigesetzt werden; wobei ggf.
  • iii) die Verbindungen der Formel IV durch Alkylierung von Verbindungen der Formel V mit R⁴X hergestellt sind, wobei X für eine Abgangsgruppe, insbesondere für Halogen OSO₂Me,
    OSO₂ Phenyl, steht und ggf.
  • iv) die Verbindungen der Formel I, sofern Q = O und NR′ gilt, in ihre Pyridin- N-oxide (I′) übergeführt werden.
8. A process for the preparation of compounds of formula I according to claims 1 to 4, in which A is a substituted alkylene part, B = CO₂H, Y = CR³ and m = 0 and 1 by
  • i1.) Pyridine-2-carboxylic acids of the formula II (R 11 = H) are reacted with the amino esters of the formula III to give the amide esters of the formula IV, or
  • i2.) Pyridine-2-carboxylic acid esters of the formula II (R¹¹ = lower alkyl) are reacted under the conditions of aminolysis to give the compounds of the formula IV; and
  • ii) the compounds of the formula I are released from their esters of the formula IV; where possibly
  • iii) the compounds of the formula IV are prepared by alkylation of compounds of the formula V with R⁴X, where X for a leaving group, especially for halogen OSO₂Me,
    OSO₂ phenyl, stands and possibly
  • iv) the compounds of the formula I, if Q = O and NR ', in their pyridine N-oxides (I') be transferred.
DE4337271A 1993-11-02 1993-11-02 ubstd. heterocyclic carboxylic acid amides and their prepn. Withdrawn DE4337271A1 (en)

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DE4337271A DE4337271A1 (en) 1993-11-02 1993-11-02 ubstd. heterocyclic carboxylic acid amides and their prepn.
ES94117018T ES2101421T3 (en) 1993-11-02 1994-10-27 SUBSTITUTED HETERO-CYCLIC CARBOXYLIC ACID AMIDES, THEIR PREPARATION AND THEIR USE AS MEDICINES.
AT94117018T ATE149486T1 (en) 1993-11-02 1994-10-27 SUBSTITUTED HETEROCYCLIC CARBOXYLIC AMIDES, THEIR PRODUCTION AND THEIR USE AS MEDICINAL PRODUCTS
DK94117018.5T DK0650961T3 (en) 1993-11-02 1994-10-27 Substituted heterocyclic carboxylic acid amides, their preparation and their use as drugs.
DE59401924T DE59401924D1 (en) 1993-11-02 1994-10-27 Substituted heterocyclic carboxamides, their preparation and their use as medicines
EP94117018A EP0650961B1 (en) 1993-11-02 1994-10-27 Substituted heterocyclic carboxylic acid amides, their preparation, and their use as medicaments
SG1996007114A SG48114A1 (en) 1993-11-02 1994-10-27 Substituted heterocycle carboxamides their preparation and their use as pharmaceuticals
PL94305646A PL179794B1 (en) 1993-11-02 1994-10-28 Substituted heterocyclic carboxylic amides, method of obtaining them and therapeutic agents containing such compounds
IL11145494A IL111454A (en) 1993-11-02 1994-10-30 Substituted heterocyclic carboxamides for use as pharmaceuticals, some such novel compounds and their preparation
MYPI94002894A MY112413A (en) 1993-11-02 1994-10-31 Substituted heterocyclic carboxamides, their preparation and their use as pharmaceuticals
NZ264821A NZ264821A (en) 1993-11-02 1994-10-31 Substituted pyridine or pyridazine carboxamide derivatives, preparation and pharmaceutical compositions thereof
UA94105979A UA41318C2 (en) 1993-11-02 1994-10-31 heterocyclic derivatives of carboxylic acid and their pharmaceutically acceptable salts
AU77564/94A AU676775B2 (en) 1993-11-02 1994-10-31 Substituted heterocyclic carboxamides, their preparation andtheir use as pharmaceuticals
CA002134866A CA2134866A1 (en) 1993-11-02 1994-11-01 Substituted heterocyclic carboxamides, their preparation and their use as pharmaceuticals
CZ19942683A CZ289356B6 (en) 1993-11-02 1994-11-01 Substituted amides of heterocyclic carboxylic acids, process of their preparation and their use as a medicament
ZA948580A ZA948580B (en) 1993-11-02 1994-11-01 Substituted heterocyclic carboxamides their preparation and their use as pharmaceuticals
NO944162A NO301880B1 (en) 1993-11-02 1994-11-01 Substituted heterocyclic carboxylic acid amides and their use in the manufacture of drugs
CN94117623A CN1107145A (en) 1993-11-02 1994-11-02 Substituted heterocyclic carboxamides, their preparation and their use as pharmaceuticals
KR1019940028871A KR950014072A (en) 1993-11-02 1994-11-02 Substituted heterocyclic carboxamides, processes for their preparation and their use as medicaments
JP6292032A JPH07228571A (en) 1993-11-02 1994-11-02 Substituted heterocyclic carboxamide, its production, and its use as medicine
TW083111257A TW399046B (en) 1993-11-02 1994-12-05 Substituted heterocyclic carboxamides, their preparation and their use as pharmaceuticals
GR970400831T GR3023174T3 (en) 1993-11-02 1997-04-18 Substituted heterocyclic carboxylic acid amides, their preparation, and their use as medicaments.
HK98105872A HK1006711A1 (en) 1993-11-02 1998-06-22 Substituted heterocyclic carboxylic acid amides their preparation and their use as medicaments
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