CS216933B2 - Method of making the heterocyclic phenoxyemines - Google Patents

Method of making the heterocyclic phenoxyemines Download PDF

Info

Publication number: CS216933B2
Authority: CS; Czechoslovakia
Prior art keywords: pyrrolidine; methoxy; compounds; mol; dried
Prior art date: 1979-07-06

Application number

CS804693A

Other languages

Czech (cs)

English (en)

Inventor

Michel Thominet

Jacqueline Franceschini

Original Assignee

Ile De France

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.)

1979-07-06

Filing date

1980-07-01

Publication date

1982-12-31

1979-07-06 Priority claimed from FR7917610A external-priority patent/FR2460935A1/fr

1980-04-01 Priority claimed from FR8007352A external-priority patent/FR2479218A2/fr

1980-07-01 Application filed by Ile De France filed Critical Ile De France

1981-02-12 Priority to CS811017A priority Critical patent/CS216934B2/cs

1982-12-31 Publication of CS216933B2 publication Critical patent/CS216933B2/cs

Links

125000000623 heterocyclic group Chemical group 0.000 title 1
238000004519 manufacturing process Methods 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 41
-1 heterocyclic phenoxyamines Chemical class 0.000 claims description 24
238000000034 method Methods 0.000 claims description 16
150000003839 salts Chemical class 0.000 claims description 12
125000000217 alkyl group Chemical group 0.000 claims description 9
125000004432 carbon atom Chemical group C* 0.000 claims description 8
238000002360 preparation method Methods 0.000 claims description 8
150000001204 N-oxides Chemical class 0.000 claims description 5
150000003242 quaternary ammonium salts Chemical class 0.000 claims description 5
239000007858 starting material Substances 0.000 claims description 5
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
125000000753 cycloalkyl group Chemical group 0.000 claims description 3
125000005843 halogen group Chemical group 0.000 claims description 3
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
125000003342 alkenyl group Chemical group 0.000 claims description 2
150000001412 amines Chemical class 0.000 claims description 2
125000000129 anionic group Chemical group 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
239000003513 alkali Substances 0.000 claims 1
229910052739 hydrogen Inorganic materials 0.000 claims 1
239000001257 hydrogen Substances 0.000 claims 1
ISWSIDIOOBJBQZ-UHFFFAOYSA-M phenolate Chemical compound [O-]C1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-M 0.000 claims 1
229940031826 phenolate Drugs 0.000 claims 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 106
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 78
239000000243 solution Substances 0.000 description 51
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 45
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 44
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
239000002585 base Substances 0.000 description 34
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 33
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 31
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
235000019441 ethanol Nutrition 0.000 description 31
239000000047 product Substances 0.000 description 31
239000000203 mixture Substances 0.000 description 28
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Natural products OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 24
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 18
238000010992 reflux Methods 0.000 description 16
229910021529 ammonia Inorganic materials 0.000 description 15
239000007864 aqueous solution Substances 0.000 description 14
206010002091 Anaesthesia Diseases 0.000 description 13
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 13
230000037005 anaesthesia Effects 0.000 description 13
238000001816 cooling Methods 0.000 description 13
229910000027 potassium carbonate Inorganic materials 0.000 description 13
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
238000006243 chemical reaction Methods 0.000 description 10
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Substances OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 10
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 9
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
238000004458 analytical method Methods 0.000 description 9
208000003251 Pruritus Diseases 0.000 description 8
KJFMBFZCATUALV-UHFFFAOYSA-N phenolphthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2C(=O)O1 KJFMBFZCATUALV-UHFFFAOYSA-N 0.000 description 8
239000000126 substance Substances 0.000 description 8
238000004809 thin layer chromatography Methods 0.000 description 8
230000003444 anaesthetic effect Effects 0.000 description 7
ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical class C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 7
230000000694 effects Effects 0.000 description 7
239000001530 fumaric acid Substances 0.000 description 7
230000007803 itching Effects 0.000 description 7
229940095064 tartrate Drugs 0.000 description 7
241000700198 Cavia Species 0.000 description 6
241001465754 Metazoa Species 0.000 description 6
238000004090 dissolution Methods 0.000 description 6
230000007794 irritation Effects 0.000 description 6
238000002844 melting Methods 0.000 description 6
230000008018 melting Effects 0.000 description 6
238000001953 recrystallisation Methods 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
OCQAXYHNMWVLRH-UHFFFAOYSA-N 2,3-dibenzoyl-2,3-dihydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(O)(C(O)=O)C(O)(C(=O)O)C(=O)C1=CC=CC=C1 OCQAXYHNMWVLRH-UHFFFAOYSA-N 0.000 description 5
RTLULEZPCUMDKR-UHFFFAOYSA-N 2-[2-(3,5-dichloro-2-methoxyphenoxy)ethyl]-1-methylpyrrolidine Chemical compound COC1=C(Cl)C=C(Cl)C=C1OCCC1N(C)CCC1 RTLULEZPCUMDKR-UHFFFAOYSA-N 0.000 description 5
YFKQRZRAQLZDAZ-UHFFFAOYSA-N 3,5-dichloro-2-methoxyphenol Chemical compound COC1=C(O)C=C(Cl)C=C1Cl YFKQRZRAQLZDAZ-UHFFFAOYSA-N 0.000 description 5
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 5
239000008346 aqueous phase Substances 0.000 description 5
238000002425 crystallisation Methods 0.000 description 5
230000008025 crystallization Effects 0.000 description 5
238000002347 injection Methods 0.000 description 5
239000007924 injection Substances 0.000 description 5
239000006210 lotion Substances 0.000 description 5
239000012071 phase Substances 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical group CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 5
229960004919 procaine Drugs 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
229910052708 sodium Inorganic materials 0.000 description 5
239000011734 sodium Substances 0.000 description 5
239000000725 suspension Substances 0.000 description 5
DBARMDUSHJFUOJ-UHFFFAOYSA-N 2-[2-(3,5-dichloro-2-methoxyphenoxy)ethyl]-1-ethylpyrrolidine Chemical compound CCN1CCCC1CCOC1=CC(Cl)=CC(Cl)=C1OC DBARMDUSHJFUOJ-UHFFFAOYSA-N 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
241000700159 Rattus Species 0.000 description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
FKCMADOPPWWGNZ-YUMQZZPRSA-N [(2r)-1-[(2s)-2-amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1B(O)O FKCMADOPPWWGNZ-YUMQZZPRSA-N 0.000 description 4
238000009835 boiling Methods 0.000 description 4
229910052801 chlorine Inorganic materials 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
238000004821 distillation Methods 0.000 description 4
238000001914 filtration Methods 0.000 description 4
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
229910000041 hydrogen chloride Inorganic materials 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
230000011514 reflex Effects 0.000 description 4
230000004044 response Effects 0.000 description 4
238000012360 testing method Methods 0.000 description 4
MZVIBFVRXORUIA-UHFFFAOYSA-N 2-[1-(cyclopropylmethyl)pyrrolidin-2-yl]ethanol Chemical compound OCCC1CCCN1CC1CC1 MZVIBFVRXORUIA-UHFFFAOYSA-N 0.000 description 3
MWFCGPKABKLWSH-UHFFFAOYSA-N 2-[2-(3,5-dichloro-2-methoxyphenoxy)ethyl]-1-ethylpyrrolidine;hydrochloride Chemical compound Cl.CCN1CCCC1CCOC1=CC(Cl)=CC(Cl)=C1OC MWFCGPKABKLWSH-UHFFFAOYSA-N 0.000 description 3
VBKJZTGQDQHOCK-UHFFFAOYSA-N 3,5-dichloro-2-ethoxyphenol Chemical compound CCOC1=C(O)C=C(Cl)C=C1Cl VBKJZTGQDQHOCK-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
241000283973 Oryctolagus cuniculus Species 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
239000002253 acid Substances 0.000 description 3
238000010533 azeotropic distillation Methods 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
239000003589 local anesthetic agent Substances 0.000 description 3
239000003208 petroleum Substances 0.000 description 3
150000002989 phenols Chemical class 0.000 description 3
238000011282 treatment Methods 0.000 description 3
239000008215 water for injection Substances 0.000 description 3
HWMNZNJLDKPDHA-WLHGVMLRSA-N (e)-but-2-enedioic acid;1-(cyclopropylmethyl)-2-[2-(3,5-dichloro-2-methoxyphenoxy)ethyl]pyrrolidine Chemical compound OC(=O)\C=C\C(O)=O.COC1=C(Cl)C=C(Cl)C=C1OCCC1N(CC2CC2)CCC1 HWMNZNJLDKPDHA-WLHGVMLRSA-N 0.000 description 2
NRSCVKWUVWTXAD-WLHGVMLRSA-N (e)-but-2-enedioic acid;2-[2-(3,5-dibromo-2-methoxyphenoxy)ethyl]-1-methylpyrrolidine Chemical compound OC(=O)\C=C\C(O)=O.COC1=C(Br)C=C(Br)C=C1OCCC1N(C)CCC1 NRSCVKWUVWTXAD-WLHGVMLRSA-N 0.000 description 2
FUQJKBLFYYGQHY-UHFFFAOYSA-N 1-cyclohexyl-4-(3,5-dichloro-2-methoxyphenoxy)azepane Chemical compound COC1=C(Cl)C=C(Cl)C=C1OC1CCN(C2CCCCC2)CCC1 FUQJKBLFYYGQHY-UHFFFAOYSA-N 0.000 description 2
UMPSXRYVXUPCOS-UHFFFAOYSA-N 2,3-dichlorophenol Chemical compound OC1=CC=CC(Cl)=C1Cl UMPSXRYVXUPCOS-UHFFFAOYSA-N 0.000 description 2
LAONXLSELHLPBP-UHFFFAOYSA-N 2,4-dibromo-6-methoxyphenol Chemical compound COC1=CC(Br)=CC(Br)=C1O LAONXLSELHLPBP-UHFFFAOYSA-N 0.000 description 2
KWVSBSBWCUGVOW-UHFFFAOYSA-N 2-(2-chloroethyl)-1-(cyclopropylmethyl)pyrrolidine;hydrochloride Chemical compound Cl.ClCCC1CCCN1CC1CC1 KWVSBSBWCUGVOW-UHFFFAOYSA-N 0.000 description 2
CLVNTYZKUHNUEF-UHFFFAOYSA-N 2-(2-chloroethyl)-1-methylpyrrolidine Chemical compound CN1CCCC1CCCl CLVNTYZKUHNUEF-UHFFFAOYSA-N 0.000 description 2
SOZROWLDUUKYNG-UHFFFAOYSA-N 2-[2-(3,5-dibromo-2-methoxyphenoxy)ethyl]-1-methylpyrrolidine Chemical compound COC1=C(Br)C=C(Br)C=C1OCCC1N(C)CCC1 SOZROWLDUUKYNG-UHFFFAOYSA-N 0.000 description 2
BCWXVDIXXWCSTC-UHFFFAOYSA-N 2-[2-(3,5-dichloro-2-ethoxyphenoxy)ethyl]-1-ethylpyrrolidine Chemical compound CCOC1=C(Cl)C=C(Cl)C=C1OCCC1N(CC)CCC1 BCWXVDIXXWCSTC-UHFFFAOYSA-N 0.000 description 2
LVEYBKZTUVWKHW-UHFFFAOYSA-N 4-(3,5-dichloro-2-methoxyphenoxy)-1-methylazepane Chemical compound COC1=C(Cl)C=C(Cl)C=C1OC1CCN(C)CCC1 LVEYBKZTUVWKHW-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
206010024438 Lichenification Diseases 0.000 description 2
NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 2
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
WRMCZVNQAGIMKN-UHFFFAOYSA-N P(=O)(O)(O)O.P(=O)(O)(O)O.N1CCCC1 Chemical compound P(=O)(O)(O)O.P(=O)(O)(O)O.N1CCCC1 WRMCZVNQAGIMKN-UHFFFAOYSA-N 0.000 description 2
229910019142 PO4 Inorganic materials 0.000 description 2
FCLZCOCSZQNREK-UHFFFAOYSA-N Pyrrolidine, hydrochloride Chemical compound Cl.C1CCNC1 FCLZCOCSZQNREK-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
230000001476 alcoholic effect Effects 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
210000003169 central nervous system Anatomy 0.000 description 2
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150000001860 citric acid derivatives Chemical class 0.000 description 2
ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
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210000002683 foot Anatomy 0.000 description 2
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NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
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239000001103 potassium chloride Substances 0.000 description 2
235000011164 potassium chloride Nutrition 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
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LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
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YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
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PCTMTFRHKVHKIS-BMFZQQSSSA-N (1s,3r,4e,6e,8e,10e,12e,14e,16e,18s,19r,20r,21s,25r,27r,30r,31r,33s,35r,37s,38r)-3-[(2r,3s,4s,5s,6r)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-19,25,27,30,31,33,35,37-octahydroxy-18,20,21-trimethyl-23-oxo-22,39-dioxabicyclo[33.3.1]nonatriaconta-4,6,8,10 Chemical compound C1C=C2C[C@@H](OS(O)(=O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2.O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 PCTMTFRHKVHKIS-BMFZQQSSSA-N 0.000 description 1
YONLFQNRGZXBBF-ZIAGYGMSSA-N (2r,3r)-2,3-dibenzoyloxybutanedioic acid Chemical compound O([C@@H](C(=O)O)[C@@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-ZIAGYGMSSA-N 0.000 description 1
YONLFQNRGZXBBF-KBPBESRZSA-N (2s,3s)-2,3-dibenzoyloxybutanedioic acid Chemical compound O([C@H](C(=O)O)[C@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-KBPBESRZSA-N 0.000 description 1
ZDXGQBUWNMFNIU-WLHGVMLRSA-N (e)-but-2-enedioic acid;2-[2-(3,5-dichloro-2-methoxyphenoxy)ethyl]-1-methylpyrrolidine Chemical compound OC(=O)\C=C\C(O)=O.COC1=C(Cl)C=C(Cl)C=C1OCCC1N(C)CCC1 ZDXGQBUWNMFNIU-WLHGVMLRSA-N 0.000 description 1
KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
SCSMALNYFAOCHI-UHFFFAOYSA-N 1-(cyclopropylmethyl)-4-(3,5-dichloro-2-methoxyphenoxy)azepane 2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.COC1=C(Cl)C=C(Cl)C=C1OC1CCN(CC2CC2)CCC1 SCSMALNYFAOCHI-UHFFFAOYSA-N 0.000 description 1
LODFCSFUYRTIDP-UHFFFAOYSA-N 1-cyclohexyl-2-[2-(3,5-dichloro-2-methoxyphenoxy)ethyl]pyrrolidine Chemical compound COC1=C(Cl)C=C(Cl)C=C1OCCC1N(C2CCCCC2)CCC1 LODFCSFUYRTIDP-UHFFFAOYSA-N 0.000 description 1
SKUOGIHTIMMCRE-UHFFFAOYSA-N 1-cyclohexyl-4-(3,5-dichloro-2-methoxyphenoxy)azepane hydrochloride Chemical compound Cl.COC1=C(Cl)C=C(Cl)C=C1OC1CCN(C2CCCCC2)CCC1 SKUOGIHTIMMCRE-UHFFFAOYSA-N 0.000 description 1
MEMQECHNVMLWST-UHFFFAOYSA-N 2-(2-chloroethyl)-1-(cyclopropylmethyl)pyrrolidine Chemical compound ClCCC1CCCN1CC1CC1 MEMQECHNVMLWST-UHFFFAOYSA-N 0.000 description 1
QTZUAGDDMDRZEJ-UHFFFAOYSA-N 2-(2-chloroethyl)-1-cyclohexylpyrrolidine Chemical compound ClCCC1CCCN1C1CCCCC1 QTZUAGDDMDRZEJ-UHFFFAOYSA-N 0.000 description 1
JYOCTPGVPKYAGP-UHFFFAOYSA-N 2-[2-(3,5-dichloro-2-methoxyphenoxy)ethyl]-1-methylpyrrolidine;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.COC1=C(Cl)C=C(Cl)C=C1OCCC1N(C)CCC1 JYOCTPGVPKYAGP-UHFFFAOYSA-N 0.000 description 1
LQUOOBUMUREJOX-UHFFFAOYSA-N 2-[2-(3,5-dichlorophenoxy)ethyl]-1-ethylpyrrolidine Chemical compound CCN1CCCC1CCOC1=CC(Cl)=CC(Cl)=C1 LQUOOBUMUREJOX-UHFFFAOYSA-N 0.000 description 1
MOEFFSWKSMRFRQ-UHFFFAOYSA-N 2-ethoxyphenol Chemical compound CCOC1=CC=CC=C1O MOEFFSWKSMRFRQ-UHFFFAOYSA-N 0.000 description 1
IQUPABOKLQSFBK-UHFFFAOYSA-N 2-nitrophenol Chemical compound OC1=CC=CC=C1[N+]([O-])=O IQUPABOKLQSFBK-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
IFVAGSWDFJJJKF-UHFFFAOYSA-N 3,5-dibromo-2-methoxyaniline Chemical compound COC1=C(N)C=C(Br)C=C1Br IFVAGSWDFJJJKF-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
KBSDLBVPAHQCRY-UHFFFAOYSA-N 307496-19-1 Chemical group C1CC=CCC1CC[Si](O1)(O2)O[Si](O3)(C4CCCC4)O[Si](O4)(C5CCCC5)O[Si]1(C1CCCC1)O[Si](O1)(C5CCCC5)O[Si]2(C2CCCC2)O[Si]3(C2CCCC2)O[Si]41C1CCCC1 KBSDLBVPAHQCRY-UHFFFAOYSA-N 0.000 description 1
XXHSVYWKZNGKSD-UHFFFAOYSA-N 4-(3,5-dichloro-2-methoxyphenoxy)-1-methylazepane hydrochloride Chemical compound Cl.COC1=C(Cl)C=C(Cl)C=C1OC1CCN(C)CCC1 XXHSVYWKZNGKSD-UHFFFAOYSA-N 0.000 description 1
QISOBCMNUJQOJU-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1NN=CC=1Br QISOBCMNUJQOJU-UHFFFAOYSA-N 0.000 description 1
PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
DFJPWKSPTXZOTL-UHFFFAOYSA-N C(=O)(O)C(O)C(O)C(=O)O.C(C)N1C(CCC1)CCOC1=C(C(=CC(=C1)Cl)Cl)OC Chemical compound C(=O)(O)C(O)C(O)C(=O)O.C(C)N1C(CCC1)CCOC1=C(C(=CC(=C1)Cl)Cl)OC DFJPWKSPTXZOTL-UHFFFAOYSA-N 0.000 description 1
ZWBBJHBFVVZPDG-UHFFFAOYSA-N CN1CCCC(CC1)OC2=C(C(=CC(=C2)Br)Br)OC Chemical compound CN1CCCC(CC1)OC2=C(C(=CC(=C2)Br)Br)OC ZWBBJHBFVVZPDG-UHFFFAOYSA-N 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
AKWLOLHBUORNEW-UHFFFAOYSA-N Cl.C(C)N1C(CCC1)CCOC1=CC(=CC(=C1)Cl)Cl Chemical compound Cl.C(C)N1C(CCC1)CCOC1=CC(=CC(=C1)Cl)Cl AKWLOLHBUORNEW-UHFFFAOYSA-N 0.000 description 1
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
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VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
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208000027418 Wounds and injury Diseases 0.000 description 1
ZEEBGORNQSEQBE-UHFFFAOYSA-N [2-(3-phenylphenoxy)-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound C1(=CC(=CC=C1)OC1=NC(=CC(=C1)CN)C(F)(F)F)C1=CC=CC=C1 ZEEBGORNQSEQBE-UHFFFAOYSA-N 0.000 description 1
210000001015 abdomen Anatomy 0.000 description 1
230000021736 acetylation Effects 0.000 description 1
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208000022531 anorexia Diseases 0.000 description 1
238000003556 assay Methods 0.000 description 1
ANHCOYQSQBAJKK-UHFFFAOYSA-N azane;2-phenylethanol Chemical compound N.OCCC1=CC=CC=C1 ANHCOYQSQBAJKK-UHFFFAOYSA-N 0.000 description 1
230000031709 bromination Effects 0.000 description 1
238000005893 bromination reaction Methods 0.000 description 1
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125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
238000005660 chlorination reaction Methods 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
239000008199 coating composition Substances 0.000 description 1
229960003920 cocaine Drugs 0.000 description 1
PIQVDUKEQYOJNR-VZXSFKIWSA-N cocaine hydrochloride Chemical compound [Cl-].O([C@H]1C[C@@H]2CC[C@@H]([NH+]2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 PIQVDUKEQYOJNR-VZXSFKIWSA-N 0.000 description 1
229960003771 cocaine hydrochloride Drugs 0.000 description 1
238000004040 coloring Methods 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
239000010949 copper Substances 0.000 description 1
ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
230000006378 damage Effects 0.000 description 1
230000006196 deacetylation Effects 0.000 description 1
238000003381 deacetylation reaction Methods 0.000 description 1
238000010908 decantation Methods 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
206010061428 decreased appetite Diseases 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
150000008049 diazo compounds Chemical class 0.000 description 1
229960003887 dichlorophen Drugs 0.000 description 1
YIDKJPKYCLMJQW-AATRIKPKSA-N diethyl (e)-hex-3-enedioate Chemical compound CCOC(=O)C\C=C\CC(=O)OCC YIDKJPKYCLMJQW-AATRIKPKSA-N 0.000 description 1
230000008034 disappearance Effects 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
238000001035 drying Methods 0.000 description 1
238000005530 etching Methods 0.000 description 1
HWFPYJUTKGAQAY-UHFFFAOYSA-N ethyl 2-[1-(cyclopropylmethyl)-5-oxopyrrolidin-2-yl]acetate Chemical compound CCOC(=O)CC1CCC(=O)N1CC1CC1 HWFPYJUTKGAQAY-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
210000000245 forearm Anatomy 0.000 description 1
239000003193 general anesthetic agent Substances 0.000 description 1
244000144993 groups of animals Species 0.000 description 1
229960001867 guaiacol Drugs 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
125000006038 hexenyl group Chemical group 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
210000000548 hind-foot Anatomy 0.000 description 1
WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 1
229940091173 hydantoin Drugs 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
208000027866 inflammatory disease Diseases 0.000 description 1
208000014674 injury Diseases 0.000 description 1
238000011081 inoculation Methods 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
206010022437 insomnia Diseases 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
VRIVJOXICYMTAG-IYEMJOQQSA-L iron(ii) gluconate Chemical compound [Fe+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O VRIVJOXICYMTAG-IYEMJOQQSA-L 0.000 description 1
230000003902 lesion Effects 0.000 description 1
231100000636 lethal dose Toxicity 0.000 description 1
238000002690 local anesthesia Methods 0.000 description 1
229960005015 local anesthetics Drugs 0.000 description 1
239000000463 material Substances 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
CEQFOVLGLXCDCX-WUKNDPDISA-N methyl red Chemical compound C1=CC(N(C)C)=CC=C1\N=N\C1=CC=CC=C1C(O)=O CEQFOVLGLXCDCX-WUKNDPDISA-N 0.000 description 1
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
229960002216 methylparaben Drugs 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
210000001640 nerve ending Anatomy 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
238000010899 nucleation Methods 0.000 description 1
208000030212 nutrition disease Diseases 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
230000000399 orthopedic effect Effects 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
KYKNRZGSIGMXFH-ZVGUSBNCSA-M potassium bitartrate Chemical compound [K+].OC(=O)[C@H](O)[C@@H](O)C([O-])=O KYKNRZGSIGMXFH-ZVGUSBNCSA-M 0.000 description 1
239000001472 potassium tartrate Substances 0.000 description 1
229940111695 potassium tartrate Drugs 0.000 description 1
235000011005 potassium tartrates Nutrition 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
238000012545 processing Methods 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
238000000746 purification Methods 0.000 description 1
238000006722 reduction reaction Methods 0.000 description 1
239000013558 reference substance Substances 0.000 description 1
231100000241 scar Toxicity 0.000 description 1
210000003497 sciatic nerve Anatomy 0.000 description 1
230000007017 scission Effects 0.000 description 1
238000007790 scraping Methods 0.000 description 1
238000007789 sealing Methods 0.000 description 1
239000000932 sedative agent Substances 0.000 description 1
230000001624 sedative effect Effects 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
NESLWCLHZZISNB-UHFFFAOYSA-M sodium phenolate Chemical compound [Na+].[O-]C1=CC=CC=C1 NESLWCLHZZISNB-UHFFFAOYSA-M 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000002904 solvent Substances 0.000 description 1
238000001256 steam distillation Methods 0.000 description 1
238000003756 stirring Methods 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
230000001629 suppression Effects 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
210000002303 tibia Anatomy 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
238000010200 validation analysis Methods 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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 radicals, substituted by hetero atoms, attached to ring carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings 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
- C07D223/08—Oxygen atoms

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
Neurology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Pyrrole Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Thiazole And Isothizaole Compounds (AREA)
Other In-Based Heterocyclic Compounds (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

CS804693A 1979-07-06 1980-07-01 Method of making the heterocyclic phenoxyemines CS216933B2 (en)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CS811017A CS216934B2 (cs)	1980-07-01	1981-02-12	Způsob výroby l-cyklohexenylmethyl-2-chIorethylpyrrolidinu

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
FR7917610A FR2460935A1 (fr)	1979-07-06	1979-07-06	Nouvelles phenoxyamines heterocycliques substituees, leur methode de preparation et leur application comme anesthetiques locaux
FR8007352A FR2479218A2 (fr)	1980-04-01	1980-04-01	Nouvelles phenoxyamines heterocycliques substituees, leur methode de preparation et leur application comme anesthesiques locaux

Publications (1)

Publication Number	Publication Date
CS216933B2 true CS216933B2 (en)	1982-12-31

Family

ID=26221244

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CS804693A CS216933B2 (en)	1979-07-06	1980-07-01	Method of making the heterocyclic phenoxyemines

Country Status (37)

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US (1)	US4379161A (de)
EP (2)	EP0024960B1 (de)
JP (2)	JPS5639065A (de)
AR (1)	AR224012A1 (de)
AT (2)	ATE17119T1 (de)
AU (2)	AU536482B2 (de)
BE (1)	BE884124A (de)
BG (2)	BG35039A3 (de)
CA (1)	CA1163273A (de)
CH (2)	CH648827A5 (de)
CS (1)	CS216933B2 (de)
DD (2)	DD153206A5 (de)
DE (2)	DE3071314D1 (de)
DK (1)	DK157538C (de)
ES (1)	ES8103049A1 (de)
FI (2)	FI74274C (de)
GR (1)	GR69638B (de)
HK (2)	HK55689A (de)
HU (2)	HU181147B (de)
IE (2)	IE50060B1 (de)
IL (2)	IL60472A (de)
IN (2)	IN153037B (de)
IT (1)	IT1188985B (de)
JO (1)	JO1077B1 (de)
LU (1)	LU82584A1 (de)
MA (1)	MA18893A1 (de)
MX (2)	MX7642E (de)
NO (2)	NO156086C (de)
NZ (1)	NZ194230A (de)
OA (1)	OA06561A (de)
PH (1)	PH16449A (de)
PL (1)	PL127393B1 (de)
PT (1)	PT71482A (de)
RO (2)	RO85323B (de)
SU (1)	SU1085507A3 (de)
YU (2)	YU42344B (de)
ZW (1)	ZW15280A1 (de)

Families Citing this family (12)

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FR2586018B1 (fr) *	1985-08-12	1988-03-25	Ile De France	Nouveau benzodioxepanne, son procede de synthese et ses applications en therapeutique
WO1990012004A1 (en) *	1989-04-07	1990-10-18	Fujisawa Pharmaceutical Co., Ltd.	New naphthalene compounds and method of producing the same
EP0471941A3 (en) *	1990-08-16	1992-10-14	American Cyanamid Company	An improved process for the preparation of 5-bromo-2-methoxyresorcinol
US5472958A (en) *	1994-08-29	1995-12-05	Abbott Laboratories	2-((nitro)phenoxymethyl) heterocyclic compounds that enhance cognitive function
US7799337B2 (en) *	1997-07-21	2010-09-21	Levin Bruce H	Method for directed intranasal administration of a composition
DE69817214T2 (de) *	1997-11-05	2004-06-09	Neurosearch A/S	Azaring-ether-derivate und ihre verwendung als nicotinic-ach-rezeptormodulatoren
US8473062B2 (en) *	2008-05-01	2013-06-25	Autonomic Technologies, Inc.	Method and device for the treatment of headache
US8412336B2 (en) *	2008-12-29	2013-04-02	Autonomic Technologies, Inc.	Integrated delivery and visualization tool for a neuromodulation system
US8494641B2 (en) *	2009-04-22	2013-07-23	Autonomic Technologies, Inc.	Implantable neurostimulator with integral hermetic electronic enclosure, circuit substrate, monolithic feed-through, lead assembly and anchoring mechanism
US9320908B2 (en) *	2009-01-15	2016-04-26	Autonomic Technologies, Inc.	Approval per use implanted neurostimulator
US20100185249A1 (en) *	2009-01-22	2010-07-22	Wingeier Brett M	Method and Devices for Adrenal Stimulation
CN111205015B (zh) *	2020-01-20	2021-11-26	东南大学	一种高稳定泡沫混凝土发泡剂的制备方法

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US3117976A (en) *	1958-11-12	1964-01-14	Beecham Res Lab	Nu-alkyl-pyrrolidine-2-methanol, alpha cyclohexyl mandelates
FR1342756A (fr) *	1958-11-21	1963-11-15	Beecham Res Lab	Esters basiques et leur procédé de préparation, notamment le phényl-cyclohexyl-glycolate de (1-méthyl-2-pyrrolidyl) méthyle et ses sels d'addition
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LU78625A1 (de) *	1977-12-02	1979-06-13	Byk Gulden Lomberg Chem Fab	Substituierte 1-phenyl-2-pyrrolidin-2-yl-ethanole,verfahren zu ihrer herstellung,ihre verwendung und sie enthaltende arzneimittel
DE2811952A1 (de) *	1978-03-18	1979-10-31	Merck Patent Gmbh	Phenoxyalkylamine und verfahren zu ihrer herstellung

1980
- 1980-06-25 US US06/162,796 patent/US4379161A/en not_active Expired - Lifetime
- 1980-07-01 OA OA57149A patent/OA06561A/xx unknown
- 1980-07-01 YU YU1710/80A patent/YU42344B/xx unknown
- 1980-07-01 CS CS804693A patent/CS216933B2/cs unknown
- 1980-07-01 BG BG048341A patent/BG35039A3/xx unknown
- 1980-07-01 EP EP80400999A patent/EP0024960B1/de not_active Expired
- 1980-07-01 DE DE8383105420T patent/DE3071314D1/de not_active Expired
- 1980-07-01 AT AT83105420T patent/ATE17119T1/de not_active IP Right Cessation
- 1980-07-01 SU SU802938255A patent/SU1085507A3/ru active
- 1980-07-01 EP EP83105420A patent/EP0094102B1/de not_active Expired
- 1980-07-01 DE DE8080400999T patent/DE3069789D1/de not_active Expired
- 1980-07-01 BG BG062115A patent/BG35746A3/xx unknown
- 1980-07-01 AT AT80400999T patent/ATE10739T1/de not_active IP Right Cessation
- 1980-07-02 IL IL60472A patent/IL60472A/xx unknown
- 1980-07-02 BE BE1/9873A patent/BE884124A/fr not_active IP Right Cessation
- 1980-07-02 AU AU60028/80A patent/AU536482B2/en not_active Ceased
- 1980-07-02 PT PT71482A patent/PT71482A/pt unknown
- 1980-07-03 HU HU80801658A patent/HU181147B/hu not_active IP Right Cessation
- 1980-07-03 RO RO110029A patent/RO85323B/ro unknown
- 1980-07-03 RO RO101590A patent/RO81532B/ro unknown
- 1980-07-03 HU HU822217A patent/HU186539B/hu not_active IP Right Cessation
- 1980-07-03 NZ NZ194230A patent/NZ194230A/xx unknown
- 1980-07-03 AR AR281635A patent/AR224012A1/es active
- 1980-07-04 NO NO802027A patent/NO156086C/no unknown
- 1980-07-04 DK DK289580A patent/DK157538C/da not_active IP Right Cessation
- 1980-07-04 MX MX8011334U patent/MX7642E/es unknown
- 1980-07-04 MA MA19091A patent/MA18893A1/fr unknown
- 1980-07-04 CH CH5169/80A patent/CH648827A5/fr not_active IP Right Cessation
- 1980-07-04 FI FI802156A patent/FI74274C/fi not_active IP Right Cessation
- 1980-07-04 ES ES493111A patent/ES8103049A1/es not_active Expired
- 1980-07-04 IE IE1392/80A patent/IE50060B1/en not_active IP Right Cessation
- 1980-07-04 CH CH5684/84A patent/CH655100A5/fr not_active IP Right Cessation
- 1980-07-04 IE IE1653/85A patent/IE50061B1/en not_active IP Right Cessation
- 1980-07-04 MX MX80100439U patent/MX6366E/es unknown
- 1980-07-04 IT IT49163/80A patent/IT1188985B/it active
- 1980-07-04 GR GR62381A patent/GR69638B/el unknown
- 1980-07-04 PL PL1980225473A patent/PL127393B1/pl unknown
- 1980-07-04 LU LU82584A patent/LU82584A1/fr unknown
- 1980-07-04 ZW ZW152/80A patent/ZW15280A1/xx unknown
- 1980-07-05 IN IN779/CAL/80A patent/IN153037B/en unknown
- 1980-07-05 JO JO19801077A patent/JO1077B1/en active
- 1980-07-07 DD DD222455A patent/DD153206A5/de unknown
- 1980-07-07 JP JP9321680A patent/JPS5639065A/ja active Granted
- 1980-07-07 DD DD80234984A patent/DD201141A5/de not_active IP Right Cessation
- 1980-07-07 PH PH24248A patent/PH16449A/en unknown
- 1980-09-30 JP JP13751280A patent/JPS5649351A/ja active Granted
1982
- 1982-12-16 CA CA000417963A patent/CA1163273A/fr not_active Expired
- 1982-12-17 YU YU2801/82A patent/YU42824B/xx unknown
1983
- 1983-06-01 IL IL68854A patent/IL68854A0/xx not_active IP Right Cessation
- 1983-10-10 IN IN1246/CAL/83A patent/IN158706B/en unknown
1984
- 1984-03-02 AU AU25260/84A patent/AU563009B2/en not_active Ceased
1986
- 1986-05-20 NO NO861988A patent/NO861988L/no unknown
1987
- 1987-07-03 FI FI872955A patent/FI872955A/fi not_active Application Discontinuation
1989
- 1989-07-13 HK HK556/89A patent/HK55689A/xx unknown
- 1989-07-13 HK HK558/89A patent/HK55889A/xx unknown

Also Published As

Publication number	Publication date
IL68854A0 (en)	1983-10-31
IT8049163A0 (it)	1980-07-04
SU1085507A3 (ru)	1984-04-07
ATE17119T1 (de)	1986-01-15
PH16449A (en)	1983-10-12
JPH0149704B2 (de)	1989-10-25
EP0024960A2 (de)	1981-03-11
US4379161A (en)	1983-04-05
ATE10739T1 (de)	1984-12-15
IE801390L (en)	1981-01-04
ZW15280A1 (en)	1980-10-01
OA06561A (fr)	1981-07-31
PL127393B1 (en)	1983-10-31
YU42344B (en)	1988-08-31
YU42824B (en)	1988-12-31
RO85323B (ro)	1984-10-30
AU536482B2 (en)	1984-05-10
IN158706B (de)	1987-01-10
AR224012A1 (es)	1981-10-15
CA1163273A (fr)	1984-03-06
JPH0122264B2 (de)	1989-04-25
DD201141A5 (de)	1983-07-06
YU171080A (en)	1983-06-30
FI802156A (fi)	1981-01-07
EP0094102B1 (de)	1985-12-27
IE801392L (en)	1981-01-06
DE3071314D1 (en)	1986-02-06
CH648827A5 (fr)	1985-04-15
IL60472A0 (en)	1980-09-16
BG35039A3 (en)	1984-01-16
CH655100A5 (fr)	1986-03-27
NO156086C (no)	1987-07-22
ES493111A0 (es)	1981-02-16
HK55689A (en)	1989-07-21
MA18893A1 (fr)	1981-04-01
DE3069789D1 (en)	1985-01-24
JO1077B1 (en)	1982-07-10
EP0094102A3 (en)	1984-04-11
IT8049163A1 (it)	1982-01-04
FI872955A0 (fi)	1987-07-03
DD153206A5 (de)	1981-12-30
NZ194230A (en)	1983-02-15
LU82584A1 (fr)	1981-02-02
MX6366E (es)	1985-05-21
BE884124A (fr)	1981-01-05
PT71482A (fr)	1980-08-01
DK289580A (da)	1981-01-07
GR69638B (de)	1982-07-06
AU563009B2 (en)	1987-06-25
HK55889A (en)	1989-07-21
EP0024960A3 (en)	1981-06-17
FI74274B (fi)	1987-09-30
IE50060B1 (en)	1986-02-05
DK157538C (da)	1990-06-11
RO85323A (ro)	1984-09-29
PL225473A1 (de)	1981-10-16
ES8103049A1 (es)	1981-02-16
IN153037B (de)	1984-05-26
EP0094102A2 (de)	1983-11-16
MX7642E (es)	1990-05-16
FI74274C (fi)	1988-01-11
DK157538B (da)	1990-01-22
EP0024960B1 (de)	1984-12-12
HU186539B (en)	1985-08-28
HU181147B (en)	1983-06-28
FI872955A (fi)	1987-07-03
IT1188985B (it)	1988-01-28
YU280182A (en)	1983-06-30
BG35746A3 (en)	1984-06-15
RO81532A (ro)	1983-04-29
AU6002880A (en)	1981-01-15
NO156086B (no)	1987-04-13
NO802027L (no)	1981-01-07
AU2526084A (en)	1984-07-26
IE50061B1 (en)	1986-02-05
JPS5639065A (en)	1981-04-14
IL60472A (en)	1983-09-30
RO81532B (ro)	1983-04-30
NO861988L (no)	1981-01-07
JPS5649351A (en)	1981-05-02

Publication	Publication Date	Title
CS216933B2 (en)	1982-12-31	Method of making the heterocyclic phenoxyemines
NL8003601A (nl)	1981-01-13	Amino-etheroxyden, werkwijze voor de bereiding hiervan en de toepassing als geneesmiddel.
DE3402060A1 (de)	1985-08-01	Substituierte 5,11-dihydro-6h-dibenz(b,e)azepin-6-one, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel
PT87854B (pt)	1992-10-30	Processo para a preparacao de derivados de tio-ureia
DE2711981A1 (de)	1977-09-29	Phenaethylaminderivate und diese verbindungen enthaltende bronchodilatorisch wirksame arzneimittel
CA1139763A (fr)	1983-01-18	Procede d'obtention de nouveaux aryltrifluoroethanols
DD283602A5 (de)	1990-10-17	Verfahren zur herstellung von verbindungen und deren verwendung
DE2348973B2 (de)	1979-08-16	1 -(m-Trifluormethylphenyl)-4-propylpiperazin-derivate, Verfahren zur ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel
PT100216B (pt)	1999-06-30	N-{{4,5-di-hidroxi- e 4,5,8-tri-hidroxi-9,10-di-hidro-9,10-dioxo-2-antracentil} carbonil}-aminoacidos uteis na terapia de afeccoes osteoarticulares, processo para a sua preparacao e composicoes farmaceuticas que os contem
DE2026080C3 (de)	1979-11-15	5-Methyl-10-( ß -alkylaminoäthyl)- dibenzothiazepine, Verfahren zu ihrer Herstellung sowie pharmazeutische Zusammensetzungen
DE2909742A1 (de)	1979-09-27	Neue derivate des phenyl-alanins, deren herstellung, sowie deren therapeutische verwendung
US4594428A (en)	1986-06-10	Novel substituted heterocyclic amines and methods of preparation thereof
JPH037670B2 (de)	1991-02-04
US4333930A (en)	1982-06-08	Orthoarylideneaminophenethylamines and pharmaceutical compositions
DE2618936B2 (de)	1978-09-07	N-Acyl-glutamine, Verfahren zu ihrer Herstellung und sie enthaltende pharmazeutische Zubereitungen
KR840001238B1 (ko)	1984-08-23	신규 치환 헤테로사이클 페녹시아민의 제조방법
DE1593392C3 (de)	1979-03-15	Neue vom 9,10-Äthano-9,10-dihydroanthracen abgeleitete Aminoäther und deren Salze sowie Verfahren zu ihrer Herstellung
DE1595870A1 (de)	1970-03-12	Verfahren zur Herstellung von 3-(o-Methoxyphenoxy)-1,2-propandiolnicotinaten und deren Salzen
CA1161435A (fr)	1984-01-31	Phenoxyamines heterocycliques substituees, leur methode de preparation et leur application comme anesthesiques locaux
DE1901167C3 (de)	1977-11-03	Substituierte Indole, Verfahren zu ihrer Herstellung und pharmazeutische Zusammensetzungen
Gardner et al.	1933	Some New Local Anesthetics Containing the Morpholine Ring. II1
DE2854341A1 (de)	1979-06-28	Neue derivate der 2- eckige klammer auf (4-chinolinyl)-amino eckige klammer zu -5-fluorbenzoesaeure, verfahren zu deren herstellung, deren verwendung als arzneimittel und die sie enthaltenden pharmazeutischen zusammensetzungen
CH635584A5 (en)	1983-04-15	Process for preparing novel benzoylpiperidylalkyl indoles and related compounds
FR2460935A1 (fr)	1981-01-30	Nouvelles phenoxyamines heterocycliques substituees, leur methode de preparation et leur application comme anesthetiques locaux
Cohen et al.	1952	840. Synthetical experiments in the B group of vitamins. Part VI. Synthesis of the pyridoxine analogue, 2-benzyl-3-hydroxy-4: 5-bis-hydroxymethylpyridine