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WO1993012086A1 - Derive d'arylamide - Google Patents

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Publication number
WO1993012086A1
WO1993012086A1 PCT/JP1992/001614 JP9201614W WO9312086A1 WO 1993012086 A1 WO1993012086 A1 WO 1993012086A1 JP 9201614 W JP9201614 W JP 9201614W WO 9312086 A1 WO9312086 A1 WO 9312086A1
Authority
WO
WIPO (PCT)
Prior art keywords
acid
piperidine
naphthalenecarbonyl
naphthalenesulfonyl
phenoxy
Prior art date
Application number
PCT/JP1992/001614
Other languages
English (en)
Japanese (ja)
Inventor
Teruo Komoto
Hiroyuki Hirota
Susumu Sato
Mari Ohtsuka
Hidehiko Kohya
Hiroyuki Mizuno
Tadayuki Kuraishi
Original Assignee
Ss Pharmaceutical Co., Ltd.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Ss Pharmaceutical Co., Ltd. filed Critical Ss Pharmaceutical Co., Ltd.
Publication of WO1993012086A1 publication Critical patent/WO1993012086A1/fr

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Classifications

    • 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
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/70—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
    • C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
    • C07D211/40—Oxygen atoms
    • C07D211/44—Oxygen atoms attached in position 4
    • C07D211/52—Oxygen atoms attached in position 4 having an aryl radical as the second substituent in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/92—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with a hetero atom directly attached to the ring nitrogen atom
    • C07D211/96—Sulfur atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/22—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with hetero atoms directly attached to ring nitrogen atoms
    • C07D295/26—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Definitions

  • the present invention provides a novel aryl amide derivative or a salt thereof, and an excellent A circulatory agent with vasodilator and antilipidemic effects
  • Thromboxane A 2 (hereinafter abbreviated as “TXA 2 ”) is one of the metabolites of arachidonic acid cascade, and its major effects are known to have blood J ⁇ * effects and vasoconstrictor effects. ing.
  • an object of the present invention is to provide a circulating agent having a strong blood-swelling inhibitory action, a vasodilating action and an anti-lipidemia action.
  • the present inventor synthesized a large number of arylamide derivatives, and conducted a study on their compatibility with respect to their blood / J storage inhibitory action, vasodilatory action and anti-hyperlipidemic action.
  • the arylamide ⁇ form represented by m-, (i) or a salt thereof has an excellent blood J «» production due to ⁇ XA 2 receptor 3 ⁇ 4inhibition «, has a vascular effect, and has an anti-hyperlipidemic effect. It has high and low cost and is useful as a drug for various circulations such as thrombosis, myocardial infarction, atherosclerosis, and high female ii ⁇ Effl! /
  • the present invention has been completed.
  • the present invention provides the following " ⁇ (1)
  • R 4 represents a peracid group or one NH (CH 2 ) m C0 (3H, wherein m represents a number of 1 to 3); It is a circulating agent containing
  • the arylamide of the present invention is in the form of a stomach to «(1).
  • the straight-chain IX of the numbers 1 to 6 is preferably a branched chain, Specific examples include methyl, ethyl, II-propyl, i-propyl, II-butyl, i-butyl, t-butyl, n-pentyl, i-pentyl, II- Examples of xy halogen include tl halogen atoms include fluorine atom, chlorine atom, atom and iodine atom.U alkyl group substituted by halogen atom includes trifluoromethyl group, 1,1,1,1-trifluorofluorene Examples of carboxyalkyloxy groups include carboxymethyloxy, carboxyethyloxy, and carboxypropyloxy. Also, as the alkoxy group
  • Self-alkyl groups having an atom bonded thereto include alkenyl groups such as vinyl group, propenyl group, aryl group, branyl group, and pentenyl; and acylamino groups such as formylamino group, acetoamino group, Examples include a propionylamino group or a butyrylamino group.
  • alkylene group having 1 to 3 include a methylene group, an ethylene group, and a propylene group.
  • Examples of the salts of rylamid (1) include salts of inorganic acids, inorganic acid salts, and organic acid salts. More specifically, lithium salts include lithium salts, sodium salts, potassium salts, magnesium salts, and the like. Inorganic acid salts include hydrochlorides, sulfates, nitrates, hydrobromides, and phosphorus salts. Examples of the organic acid salts include: organic acid salts such as succinate, oxalate, citrate, lincoate, fumarate, maleate, succinate, lactate, 3 ⁇ 4salt, and methanesulfonic acid. Benzenesulfonate, p-toluenesulfonate and the like.
  • Specific examples of the present invention (1) include the following.
  • the arylamide derivative (1) of the present invention can be prepared, for example, according to the following traces 1 to 5. SiS expression 1
  • A represents a halogen atom
  • R 7 represents an alkylyl group
  • Ar, X, ⁇ , and m have the same meaning as described above.
  • 1-arylpyrazine derivative (2) is traced with arylsulfonyl halide or arylcarbonylhalide (3), and is converted into Iridyl I (4). 5) Get. Next, it is converted to ⁇ ! (5) ⁇ ! By reacting (6), the arylamide derivative (1a) of the present invention can be obtained. further
  • the amino acid ⁇ S form (7) is traced to (l a) to form a compound ⁇ ! (8), and this is hydrolyzed to give the aryl amide ⁇ »form (lb) of the present invention.
  • the 1-arylpyrazine compound (2) is combined with an acetyl sulfonyl halide or an arylcarbonyl halide (3) by the following formula: tetrahydrofuran, benzene, toluene, ether, chloroform, methylene chloride, etc.
  • a base such as triethylamine, pyridine or the like
  • Demethylation of lig (4) is carried out by using nadanaka, ethanethiol Z non-aluminum aluminum chloride, boron chloride, and tertiary boron: 0 * C to room temperature.
  • a pyridinium salt such as pyridine salt ⁇ and 130 to 20 O :.
  • (1a) and the compound ⁇ ! (7) are the same as those in methylene pentane, chloroform, tetrahydrofuran, benzene, toluene, ether, etc .; It is preferable to carry out the reaction at 0 to room temperature under the presence of a base.
  • 1-benzyl-1-pyridone (9) was traced with aryl magnesium halide (10), and was converted to iridani (11).
  • 4-arylpyridine derivative (13) the arylsulfonyl halide or arylcarbonyl halide is (3) is converted to ⁇ (14), which is demethylated to obtain ⁇ (15).
  • the compound (!) (15) is converted to the compound (!)
  • the arylamide derivative (1c) of the present invention can be obtained.
  • the amino acid derivative is added to (1c).
  • TD-luamide test product (1d) of the present invention By subjecting (7) to a chemical formula (16), which is subjected to Kana-degradation, a TD-luamide test product (1d) of the present invention can be obtained.
  • the Si ⁇ of 1-benzyl-4-pyridone (9) and aryl magnesium halide (10) is produced as normal Grignard in ⁇ of tetrahydrofuran, ether, etc.
  • the compound (21) is converted to the compound (24) and hydrolyzed to give the arylamide (1e) of the present invention.
  • the arylamide (I f) Ji ⁇ of the present invention can be obtained. More specifically, to produce compound (18) by reacting 1-penziru 4-piperidone (9) with aryl magnesium hydride (17), the compound (9) to (11) of the reaction formula 2 is obtained. What is necessary is just to carry out according to the method of obtaining. From compound (18) to (19) ⁇ 3 ⁇ 4 ⁇ ⁇ & can be performed according to the method of obtaining formula (13) from formula (12):
  • the conversion of chemical formulas (19) to (20) can be carried out in accordance with the chemical formulas (2) to (4) of formula 1, and the hydrolysis of chemical formulas (20) and (22) ⁇ 8 (8) can be performed in accordance with (1 b).
  • the reaction from compound (21) to (1e) and (22) can be carried out according to J3 ⁇ 4S in formulas (5) to (1a) of reaction formula 1, and from (21) to (23).
  • S ⁇ S to ()) must be done according to the law of Eq. 2 ⁇ !
  • the trace from (23) to af) must be 5) It can be done according to the legality of (la).
  • bis (2-haloethyl) amine hydrochloride (26) is allowed to S ⁇ to the arylaminocarboxylic acid derivative (25), resulting in i-Dari ⁇ ! (27), and reacted with arylsulfonyl halide or arylcarbonylcarbonyl halide (3).
  • SiS of arylaminocarboxylic acid ( ⁇ ) (25) and bis (2-haloethyl) amine hydrochloride (26) can be obtained in a solvent such as tetrahydrofuran, benzene, toluene, ethanol, methanol, etc. It is carried out under heating of a base such as triethylamine or pyridine.
  • Traces from (27) to (28) can be carried out according to the reaction of trace formula 1 ⁇ ! (2) to (4), and hydrolysis of (28) can be converted to trace formula 1.
  • the arylhalogeno derivative (29) is converted to Mg and S to form Grignard ugly (30), which is then converted to 1-benzyl-14-piperidone (9) ⁇ f (31) is obtained. Next, this is hydrolyzed to give ⁇ ⁇ (32), which is reduced to give ⁇ (33). Further, when arylaryl sulfonyl halide or aryl sulfonyl halide (3) is used, the arylamide of the present invention (1h) can be obtained.
  • Grignard weave (30), ether Ariruharogeno derivative (29), f3 ⁇ 43 ⁇ 4 a while ⁇ to jgiK such Te tetrahydrofuran, 1 2 lower Mg and power of a catalytic amount! ⁇ Can be prepared by reflux.
  • the conversion (9) and the Grignard difficulty (30) can be performed by the same method as the synthesis of (11) from m ⁇ , 2 m (9).
  • the hydrolysis of lich ⁇ i (31) is carried out by adding ordinary dilute hydrochloric acid in ethanol. Do it.
  • the reduction of Idani ⁇ I (32) may be carried out using hydrogenation power ITT using palladium peroxide as a catalyst.
  • ⁇ JS from the lig ⁇ (33) to the arylamide ⁇ »-form (1h) of the present invention can be carried out according to the formulas (2) to (4) in the formula 1.
  • the thus obtained compound of the arylamide (I) of the present invention (1) can be purified by ⁇ such as Nada extraction, recrystallization and column chromatography.
  • mice per group was treated with 5 mice per group.
  • test sample ⁇ 5 shown in Table 1 below cut the tip of the tail one hour later, immediately put the mouse in the holder, and dipped about 2 cm of the tail tip vertically into 37 t of physiological saline ice.
  • the tail was raised and lowered at intervals of 15 seconds, and this was repeated until there was no bleeding.
  • the evaluation was performed by determining that the bleeding time was prolonged by 50% J3 ⁇ 4 ⁇ compared to the control group, and determining the minimum dose (MED). Table of results
  • Thromboxane A 2 (TXA 2 ) receptor ftg ⁇ action (in vitro)
  • Fibers were formed using spirally cut rat veins ⁇ :.
  • mice For the thighs, 6 mice (3 per group) with hypercholesterolemia given a diet of cholesterol monocholate for 7 days.
  • Tested ⁇ ! Was orally administered half of the dose on days 6 and 7, respectively. Then, after ⁇ , serum cholesterol release was measured, and 15% JiLh Serum cholesterol was determined to be Eri.
  • the minimum amount (MED) is shown in Table 3.
  • the arylamide body of the present invention (1) has an excellent bleeding time prolonging action, a blood / J ⁇ i ⁇ inhibitory action based on a thromboxane A 2 receptor withdrawal action, a vasodilatory action, and a cholesterol reduction. Has an action.
  • arylamide derivative (1) of the present invention was safe without any death even when orally administered 30 O mgZkg to mice.
  • the dose varies depending on the patient's age, age, U, administration method, physical condition, medical condition, and the like.
  • oral administration 10 to 200 tng / day
  • parenteral administration 0.1 to 2 Omg / day is appropriate.
  • the arylamide derivative (1) of the present invention may be prepared in the usual manner by using tablets, granules, hard capsules, soft capsules, inverts, fine granules, pills, suspensions, bodies, inversions, or sylobes. It can be used as a pharmaceutical preparation in various dosage forms such as an agent.
  • the arylamide derivative (1) of the present invention may be added to the ararylamide derivative (1) according to the present invention, and furthermore, disintegrants, lubricants, paving, fillers, coating agents, sugars, etc. After the addition of ⁇ ⁇ M or the like, it is preferable to prepare tablets, granules, inversions, capsules, etc.
  • the arylamide derivative (1) may be previously dissolved and dispersed in an aqueous carrier such as distilled water for bone marrow, emulsified, or the like, or may be made into a powder for starvation and then dissolved upon use. Examples of the method of administering the agent include intravenous administration, intravenous administration, intravenous administration, intramuscular administration, and subcutaneous administration.
  • Tables 4 to 7 show 1 ⁇ , the chemical formulas ⁇ ! Obtained in Examples 1 to 4, and the data of the ⁇ ⁇ based on these examples.
  • the ⁇ -J-lamide test body (1) of the present invention has a strong bleeding time awakening action, and also has a blood, inhibitory action, and vascular action based on a thromboxane A 2 receptor Mi3 ⁇ 4 action, In addition, due to its anti-lipidemia effect, circulatory effects such as cerebral thrombosis, wmm, pulmonary hemorrhage, etc. It is useful for treating and preventing the disease.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Hydrogenated Pyridines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Dérivé d'arylamide répondant à la formule générale (I), ou son sel, et médicament destiné aux organes cardio-vasculaires. Dans ladite formule (I), Ar représente (a), naphtyle, pyridinyle, furyle, thiényle, quinolyle ou indolyle; X représente -CO- ou -SO2-; Y représente (b), (c), (d) ou (e); Q représente -O- ou une liaison simple; Z représente alkylène; et R4 représente OH ou -NH(CH¿2?)mCOOH. Le dérivé ou le sel présente de puissantes activités d'inhibition de l'agglutination plaquettaire, de vasodilatation et de résistance à l'hyperlipidémie, et peut donc être utilisé dans le traitement et la prophylaxie des thromboses, des embolies, des artérioscléroses, des hypertensions, et ainsi de suite.
PCT/JP1992/001614 1991-12-11 1992-12-10 Derive d'arylamide WO1993012086A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP32748291 1991-12-11
JP3/327482 1991-12-11

Publications (1)

Publication Number Publication Date
WO1993012086A1 true WO1993012086A1 (fr) 1993-06-24

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PCT/JP1992/001614 WO1993012086A1 (fr) 1991-12-11 1992-12-10 Derive d'arylamide

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Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0607536A1 (fr) * 1992-12-08 1994-07-27 Ss Pharmaceutical Co., Ltd. Dérivés arylamidiques
WO2004048334A1 (fr) * 2002-11-26 2004-06-10 Pfizer Products Inc. Composes de piperidine phenyle a substitution phenyle s'utilisant comme activateurs de ppar
WO2006105127A2 (fr) * 2005-03-31 2006-10-05 Takeda San Diego, Inc. Inhibiteurs de l'hydroxysteroide deshydrogenase
WO2007037187A1 (fr) * 2005-09-27 2007-04-05 Shionogi & Co., Ltd. Dérivé sulfonamide ayant une activité antagoniste de récepteur pgd2
WO2007070506A2 (fr) * 2005-12-14 2007-06-21 Amgen Inc. Derives diaza heterocycliques de sulfonamide et leurs utilisations
WO2007146838A3 (fr) * 2006-06-09 2008-03-13 Icos Corp Acides phénylacétiques substitués utilisés en tant qu'antagonistes de dp-2
JP2008520637A (ja) * 2004-11-23 2008-06-19 アストラゼネカ・アクチエボラーグ 呼吸器疾患の処置に有用なフェノキシ酢酸誘導体
US7632838B2 (en) * 2006-02-07 2009-12-15 Wyeth 11-beta HSD1 inhibitors
US8003703B2 (en) 2003-08-21 2011-08-23 Astrazeneca Ab Phenoxiacetic acid derivatives
US8008350B2 (en) 2005-10-06 2011-08-30 Astrazeneca Ab Biphenyloxyacetic acid derivatives for the treatment of respiratory disease
US8022248B2 (en) 2004-07-08 2011-09-20 Astrazeneca Ab Substituted acids for the treatment of respiratory diseases
US8148572B2 (en) 2005-10-06 2012-04-03 Astrazeneca Ab Compounds
US8158820B2 (en) 2003-04-07 2012-04-17 Astrazeneca Ab Compounds
US8163727B2 (en) 2004-08-24 2012-04-24 Astrazeneca Ab Biphenyloxyacetic acid derivatives for the treatment of respiratory disease
CN101273013B (zh) * 2005-09-27 2013-06-12 盐野义制药株式会社 具有pgd2受体拮抗活性的磺酰胺衍生物
US8507544B2 (en) 2007-07-05 2013-08-13 Astrazeneca Ab Bi-aryl amide compounds as CRTh2 receptor modulators
JP5305462B2 (ja) * 2007-03-27 2013-10-02 塩野義製薬株式会社 Ｎ−フェニル−ｎ’−フェニルスルホニルピペラジン誘導体の製造方法
US10961238B2 (en) * 2016-10-26 2021-03-30 E-Therapeutics Plc Modulators of hedgehog (Hh) signaling pathway

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US3801581A (en) * 1969-06-05 1974-04-02 Ciba Geigy Corp Alpha-phenyl-fatty acids substituted by azacycloalkyl residues and their derivatives
JPS5872575A (ja) * 1981-10-08 1983-04-30 ベ−リンガ−・マンハイム・ゲゼルシヤフト・ミツト・ベシユレンクテル・ハフツング 新規カルボン酸誘導体、その製法及びこれを含有する血中脂質低下剤
JPS6144817A (ja) * 1984-08-08 1986-03-04 Otsuka Pharmaceut Co Ltd 強心剤
JPH0141128B2 (fr) * 1981-11-20 1989-09-04 Otsuka Pharma Co Ltd

Patent Citations (4)

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Publication number Priority date Publication date Assignee Title
US3801581A (en) * 1969-06-05 1974-04-02 Ciba Geigy Corp Alpha-phenyl-fatty acids substituted by azacycloalkyl residues and their derivatives
JPS5872575A (ja) * 1981-10-08 1983-04-30 ベ−リンガ−・マンハイム・ゲゼルシヤフト・ミツト・ベシユレンクテル・ハフツング 新規カルボン酸誘導体、その製法及びこれを含有する血中脂質低下剤
JPH0141128B2 (fr) * 1981-11-20 1989-09-04 Otsuka Pharma Co Ltd
JPS6144817A (ja) * 1984-08-08 1986-03-04 Otsuka Pharmaceut Co Ltd 強心剤

Cited By (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0607536A1 (fr) * 1992-12-08 1994-07-27 Ss Pharmaceutical Co., Ltd. Dérivés arylamidiques
US5411972A (en) * 1992-12-08 1995-05-02 Ss Pharmaceutical Co., Ltd. Arylamide derivatives for treating hyperlipemia
CN1035178C (zh) * 1992-12-08 1997-06-18 爱斯制药株式会社 芳酰胺衍生物
US7199243B2 (en) 2002-11-26 2007-04-03 Pfizer Inc. Piperidine compounds useful as PPAR activators
WO2004048334A1 (fr) * 2002-11-26 2004-06-10 Pfizer Products Inc. Composes de piperidine phenyle a substitution phenyle s'utilisant comme activateurs de ppar
CN100439337C (zh) * 2002-11-26 2008-12-03 辉瑞产品公司 作为ppar活化剂的苯基取代的哌啶化合物
EA008928B1 (ru) * 2002-11-26 2007-08-31 Пфайзер Продактс Инк. Активаторы рецепторов, активируемых пролифератором пероксисом (ppar )
NL1024881C2 (nl) * 2002-11-26 2009-09-16 Pfizer Prod Inc PPAR-activatoren.
US8158820B2 (en) 2003-04-07 2012-04-17 Astrazeneca Ab Compounds
US8394986B2 (en) 2003-08-21 2013-03-12 Astrazeneca Ab Phenoxiacetic acid derivatives
US8003703B2 (en) 2003-08-21 2011-08-23 Astrazeneca Ab Phenoxiacetic acid derivatives
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