RU1816282C - Способ получени производных 2-аминоалкилтиометил-1,4-дигидропиридина или их энантиомеров - Google Patents
Способ получени производных 2-аминоалкилтиометил-1,4-дигидропиридина или их энантиомеровInfo
- Publication number
- RU1816282C RU1816282C SU884613190A SU4613190A RU1816282C RU 1816282 C RU1816282 C RU 1816282C SU 884613190 A SU884613190 A SU 884613190A SU 4613190 A SU4613190 A SU 4613190A RU 1816282 C RU1816282 C RU 1816282C
- Authority
- RU
- Russia
- Prior art keywords
- methyl
- nitro
- dihydropyridine
- methoxycarbonyl
- methylthio
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title abstract 2
- 230000003287 optical effect Effects 0.000 title description 2
- -1 derivatives of nitrogen-containing heterocyclic compounds Chemical class 0.000 abstract description 63
- 150000001875 compounds Chemical class 0.000 abstract description 17
- 238000000034 method Methods 0.000 abstract description 15
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 abstract description 8
- 230000003276 anti-hypertensive effect Effects 0.000 abstract description 6
- 238000002360 preparation method Methods 0.000 abstract description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 4
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 abstract description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 abstract description 3
- 125000004093 cyano group Chemical group *C#N 0.000 abstract description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract description 3
- ORTFAQDWJHRMNX-UHFFFAOYSA-M oxidooxomethyl Chemical compound [O-][C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-M 0.000 abstract description 3
- WEMXRTXQKRXSIO-UHFFFAOYSA-N propanenitrile Chemical compound [CH2]CC#N WEMXRTXQKRXSIO-UHFFFAOYSA-N 0.000 abstract description 3
- RLKBOGLIOLFMEK-NSCUHMNNSA-N amino (e)-but-2-enoate Chemical compound C\C=C\C(=O)ON RLKBOGLIOLFMEK-NSCUHMNNSA-N 0.000 abstract description 2
- 238000002955 isolation Methods 0.000 abstract description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 abstract description 2
- 230000003647 oxidation Effects 0.000 abstract description 2
- 238000007254 oxidation reaction Methods 0.000 abstract description 2
- XMVJITFPVVRMHC-UHFFFAOYSA-N roxarsone Chemical group OC1=CC=C([As](O)(O)=O)C=C1[N+]([O-])=O XMVJITFPVVRMHC-UHFFFAOYSA-N 0.000 abstract description 2
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 abstract 2
- 238000003776 cleavage reaction Methods 0.000 abstract 1
- 150000002391 heterocyclic compounds Chemical class 0.000 abstract 1
- 150000002576 ketones Chemical class 0.000 abstract 1
- 238000007363 ring formation reaction Methods 0.000 abstract 1
- 230000007017 scission Effects 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 46
- 238000002844 melting Methods 0.000 description 29
- 230000008018 melting Effects 0.000 description 29
- 239000000243 solution Substances 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- 239000000203 mixture Substances 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- 239000000284 extract Substances 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 241000282472 Canis lupus familiaris Species 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 230000036772 blood pressure Effects 0.000 description 4
- LDHQCZJRKDOVOX-NSCUHMNNSA-N crotonic acid Chemical compound C\C=C\C(O)=O LDHQCZJRKDOVOX-NSCUHMNNSA-N 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- LLXMXDARGVXTPP-UHFFFAOYSA-N 2-methyl-1,4-dihydropyridine Chemical compound CC1=CCC=CN1 LLXMXDARGVXTPP-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 239000002220 antihypertensive agent Substances 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000010411 cooking Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- KDZWTEVTULYVHV-UHFFFAOYSA-N ethyl 4-(2-formamidoethylsulfanyl)-3-oxobutanoate Chemical compound CCOC(=O)CC(=O)CSCCNC=O KDZWTEVTULYVHV-UHFFFAOYSA-N 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 230000001631 hypertensive effect Effects 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- PAWSVPVNIXFKOS-IHWYPQMZSA-N (Z)-2-aminobutenoic acid Chemical compound C\C=C(/N)C(O)=O PAWSVPVNIXFKOS-IHWYPQMZSA-N 0.000 description 1
- ZKIJTTNWOULCBY-UHFFFAOYSA-N 1-methyl-4h-pyridine Chemical compound CN1C=CCC=C1 ZKIJTTNWOULCBY-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- OGMADIBCHLQMIP-UHFFFAOYSA-N 2-aminoethanethiol;hydron;chloride Chemical compound Cl.NCCS OGMADIBCHLQMIP-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 1
- ZOBLAHKFBSIYCK-UHFFFAOYSA-N 2-methoxyethyl 4-(2-formamidoethylsulfanyl)-3-oxobutanoate Chemical class COCCOC(=O)CC(=O)CSCCNC=O ZOBLAHKFBSIYCK-UHFFFAOYSA-N 0.000 description 1
- UXHRTKANNFEQIU-UHFFFAOYSA-N 2-methoxyethyl 4-chloro-3-oxobutanoate Chemical class COCCOC(=O)CC(=O)CCl UXHRTKANNFEQIU-UHFFFAOYSA-N 0.000 description 1
- GMZRJXDRFQUAHT-UHFFFAOYSA-N 2-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine Chemical compound C1=CNC(C)=CC1C1=CC=CC([N+]([O-])=O)=C1 GMZRJXDRFQUAHT-UHFFFAOYSA-N 0.000 description 1
- SRWILAKSARHZPR-UHFFFAOYSA-N 3-chlorobenzaldehyde Chemical compound ClC1=CC=CC(C=O)=C1 SRWILAKSARHZPR-UHFFFAOYSA-N 0.000 description 1
- ZETIVVHRRQLWFW-UHFFFAOYSA-N 3-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC(C=O)=C1 ZETIVVHRRQLWFW-UHFFFAOYSA-N 0.000 description 1
- DEPMHZHLRPAVBB-UHFFFAOYSA-N 3-o-ethyl 5-o-methyl 2-(2-formamidoethylsulfanyl)-1,6-dimethyl-4-(3-nitrophenyl)-4h-pyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(SCCNC=O)N(C)C(C)=C(C(=O)OC)C1C1=CC=CC([N+]([O-])=O)=C1 DEPMHZHLRPAVBB-UHFFFAOYSA-N 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 101100518987 Mus musculus Pax1 gene Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- IZADRBGSUJAFGR-KPKJPENVSA-N O=CNCCSCC(=O)/C(C(=O)O)=C\C1=CC=CC(Cl)=C1 Chemical compound O=CNCCSCC(=O)/C(C(=O)O)=C\C1=CC=CC(Cl)=C1 IZADRBGSUJAFGR-KPKJPENVSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 231100000460 acute oral toxicity Toxicity 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 125000000068 chlorophenyl group Chemical group 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 229940097265 cysteamine hydrochloride Drugs 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 125000004188 dichlorophenyl group Chemical group 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- ASZXIRIWXUSMHH-UHFFFAOYSA-N ethyl 2-methyl-4H-pyridine-1-carboxylate Chemical compound CCOC(=O)N1C=CCC=C1C ASZXIRIWXUSMHH-UHFFFAOYSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- XBECWGJPSXHFCS-UHFFFAOYSA-N imidazole-1-carbaldehyde Chemical compound O=CN1C=CN=C1 XBECWGJPSXHFCS-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- PYVLYEPIXZSMQG-UHFFFAOYSA-N methyl 2-methyl-4-(3-nitrophenyl)-4h-pyridine-1-carboxylate Chemical class C1=C(C)N(C(=O)OC)C=CC1C1=CC=CC([N+]([O-])=O)=C1 PYVLYEPIXZSMQG-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- GDENSQSVDRFGSZ-UHFFFAOYSA-N n-(2-sulfanylethyl)formamide Chemical compound SCCNC=O GDENSQSVDRFGSZ-UHFFFAOYSA-N 0.000 description 1
- VEPQMSRDJHLULQ-UHFFFAOYSA-N n-[2-[(6-methyl-1,4-dihydropyridin-2-yl)sulfonyl]ethyl]formamide Chemical class CC1=CCC=C(S(=O)(=O)CCNC=O)N1 VEPQMSRDJHLULQ-UHFFFAOYSA-N 0.000 description 1
- 229960001597 nifedipine Drugs 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000006501 nitrophenyl group Chemical group 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000011458 pharmacological treatment Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 230000001603 reducing effect Effects 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- AALQBIFJJJPDHJ-UHFFFAOYSA-K trisodium;thiophosphate;dodecahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[Na+].[O-]P([O-])([O-])=S AALQBIFJJJPDHJ-UHFFFAOYSA-K 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- 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
- C07D211/80—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 two double bonds between ring members or between ring members and non-ring members
- C07D211/84—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 two 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 directly attached to ring carbon atoms
- C07D211/90—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
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D401/12—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 chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D409/04—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 directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT20965/86A IT1204421B (it) | 1986-06-27 | 1986-06-27 | 2-(aminoalchiltio)metil-1,4-diidropiridine,un metodo per la loro preparazione e composizioni farmaceutiche che le contengono |
| PCT/EP1987/000335 WO1988000187A1 (en) | 1986-06-27 | 1987-06-25 | 2-(aminoalkylthio)methyl-1,4-dihydropyridine, a method for the preparation thereof and pharmaceutical compositions containing them |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RU1816282C true RU1816282C (ru) | 1993-05-15 |
Family
ID=11174716
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SU884613190A RU1816282C (ru) | 1986-06-27 | 1988-12-26 | Способ получени производных 2-аминоалкилтиометил-1,4-дигидропиридина или их энантиомеров |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US5047414A (enExample) |
| EP (2) | EP0254064B1 (enExample) |
| JP (1) | JPH0832686B2 (enExample) |
| KR (1) | KR950002154B1 (enExample) |
| AU (1) | AU603595B2 (enExample) |
| CA (1) | CA1322753C (enExample) |
| DK (1) | DK164051C (enExample) |
| ES (1) | ES2037029T3 (enExample) |
| FI (1) | FI91149C (enExample) |
| GR (1) | GR3004954T3 (enExample) |
| HU (1) | HU201305B (enExample) |
| IT (1) | IT1204421B (enExample) |
| MX (1) | MX7134A (enExample) |
| NZ (1) | NZ220868A (enExample) |
| PH (1) | PH23208A (enExample) |
| PL (1) | PL156170B1 (enExample) |
| RU (1) | RU1816282C (enExample) |
| WO (1) | WO1988000187A1 (enExample) |
| ZA (1) | ZA874636B (enExample) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1213555B (it) * | 1986-12-11 | 1989-12-20 | Boehringer Biochemia Srl | 2 metiltiometildiidropiridine, un processo per laloro preparazione e composizioni farmaceutiche che le contengono. |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CS228917B2 (en) * | 1981-03-14 | 1984-05-14 | Pfizer | Method of preparing substituted derivatives of 1,4-dihydropyridine |
| IL68604A0 (en) * | 1982-05-21 | 1983-09-30 | Haessle Ab | Processes for preparing therapeutically active dihydropyridines and intermediates for the processes |
| PH19166A (en) * | 1982-09-04 | 1986-01-16 | Pfizer | Dihydropyridined,pharmaceutical compositions and method of use |
| PL140069B1 (en) * | 1982-12-21 | 1987-03-31 | Pfizer | Method of obtaining new derivatives of dihydropiridine |
| GB8306666D0 (en) * | 1983-03-10 | 1983-04-13 | Pfizer Ltd | Therapeutic agents |
| GR851819B (enExample) * | 1984-08-17 | 1985-11-26 | Wyeth John & Brother Ltd | |
| EP0233228A1 (en) * | 1985-08-06 | 1987-08-26 | Boehringer Mannheim Italia S.P.A. | Pharmaceutically active 2-thiomethyl-substituted-1,4-dihydropyridines |
-
1986
- 1986-06-27 IT IT20965/86A patent/IT1204421B/it active
-
1987
- 1987-06-25 AU AU76969/87A patent/AU603595B2/en not_active Ceased
- 1987-06-25 ES ES198787109116T patent/ES2037029T3/es not_active Expired - Lifetime
- 1987-06-25 WO PCT/EP1987/000335 patent/WO1988000187A1/en not_active Ceased
- 1987-06-25 JP JP62504184A patent/JPH0832686B2/ja not_active Expired - Lifetime
- 1987-06-25 HU HU873824A patent/HU201305B/hu not_active IP Right Cessation
- 1987-06-25 EP EP87109116A patent/EP0254064B1/en not_active Expired - Lifetime
- 1987-06-25 EP EP87904520A patent/EP0312541B1/en not_active Expired - Lifetime
- 1987-06-25 CA CA000540555A patent/CA1322753C/en not_active Expired - Fee Related
- 1987-06-25 KR KR1019880700205A patent/KR950002154B1/ko not_active Expired - Fee Related
- 1987-06-26 PH PH35467A patent/PH23208A/en unknown
- 1987-06-26 ZA ZA874636A patent/ZA874636B/xx unknown
- 1987-06-26 NZ NZ220868A patent/NZ220868A/xx unknown
- 1987-06-27 PL PL1987266481A patent/PL156170B1/pl unknown
- 1987-06-29 MX MX713487A patent/MX7134A/es unknown
-
1988
- 1988-02-25 DK DK099588A patent/DK164051C/da not_active IP Right Cessation
- 1988-12-21 FI FI885930A patent/FI91149C/fi not_active IP Right Cessation
- 1988-12-26 RU SU884613190A patent/RU1816282C/ru active
-
1990
- 1990-12-21 US US07/638,131 patent/US5047414A/en not_active Expired - Fee Related
-
1992
- 1992-06-18 GR GR920401276T patent/GR3004954T3/el unknown
Non-Patent Citations (1)
| Title |
|---|
| Машковский М.Д. Лекарственные средства. М,: Медицина, 1986, т. 1, с. 429. F. Brody-and P.R. Ruby Pyridines and its derivatives, Part I, pages 355-533, A. Welss benger Interscience, New Jork, 1960. * |
Also Published As
| Publication number | Publication date |
|---|---|
| PL266481A1 (en) | 1988-09-01 |
| EP0312541B1 (en) | 1992-08-26 |
| HU201305B (en) | 1990-10-28 |
| DK164051C (da) | 1992-09-28 |
| IT1204421B (it) | 1989-03-01 |
| KR880701228A (ko) | 1988-07-26 |
| MX7134A (es) | 1993-10-01 |
| ES2037029T3 (es) | 1993-06-16 |
| FI885930L (fi) | 1988-12-21 |
| FI91149B (fi) | 1994-02-15 |
| IT8620965A0 (it) | 1986-06-27 |
| PL156170B1 (pl) | 1992-02-28 |
| HUT49572A (en) | 1989-10-30 |
| AU603595B2 (en) | 1990-11-22 |
| DK164051B (da) | 1992-05-04 |
| US5047414A (en) | 1991-09-10 |
| DK99588D0 (da) | 1988-02-25 |
| JPH01503065A (ja) | 1989-10-19 |
| ZA874636B (en) | 1988-03-30 |
| AU7696987A (en) | 1988-01-29 |
| FI91149C (fi) | 1994-05-25 |
| PH23208A (en) | 1989-06-06 |
| EP0254064B1 (en) | 1992-06-17 |
| WO1988000187A1 (en) | 1988-01-14 |
| KR950002154B1 (ko) | 1995-03-14 |
| NZ220868A (en) | 1989-10-27 |
| EP0254064A1 (en) | 1988-01-27 |
| GR3004954T3 (enExample) | 1993-04-28 |
| DK99588A (da) | 1988-02-25 |
| CA1322753C (en) | 1993-10-05 |
| JPH0832686B2 (ja) | 1996-03-29 |
| EP0312541A1 (en) | 1989-04-26 |
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