GB1591089A - 1,4-dihydropyridine derivatives and process for preparation thereof - Google Patents

1,4-dihydropyridine derivatives and process for preparation thereof Download PDF

Info

Publication number: GB1591089A
Authority: GB; United Kingdom
Prior art keywords: methyl; compound according; methoxycarbonyl; cyano; formyl
Prior art date: 1976-12-17
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired

Application number

GB52720/76A

Other languages

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Fujisawa Pharmaceutical Co Ltd

Original Assignee

Fujisawa 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.)

1976-12-17

Filing date

1976-12-17

Publication date

1981-06-10

1976-07-02 Priority to CA256,210A priority Critical patent/CA1080223A/en

1976-12-17 Application filed by Fujisawa Pharmaceutical Co Ltd filed Critical Fujisawa Pharmaceutical Co Ltd

1976-12-17 Priority to GB52720/76A priority patent/GB1591089A/en

1977-12-15 Priority to MX689277U priority patent/MX5273E/es

1977-12-16 Priority to SE7714374A priority patent/SE7714374L/xx

1977-12-16 Priority to HU77FU358A priority patent/HU176454B/hu

1977-12-16 Priority to JP52152290A priority patent/JPS5948828B2/ja

1977-12-16 Priority to BE183553A priority patent/BE861964A/xx

1977-12-16 Priority to DE19772756226 priority patent/DE2756226A1/de

1977-12-16 Priority to ES465137A priority patent/ES465137A1/es

1977-12-16 Priority to FR7738126A priority patent/FR2374307A1/fr

1977-12-16 Priority to DK563377A priority patent/DK563377A/da

1977-12-16 Priority to CH1553477A priority patent/CH633266A5/de

1977-12-16 Priority to AU31657/77A priority patent/AU518206B2/en

1977-12-16 Priority to AR270392A priority patent/AR221478A1/es

1977-12-16 Priority to AT0901877A priority patent/AT367401B/de

1977-12-19 Priority to ZA00777532A priority patent/ZA777532B/xx

1977-12-19 Priority to NL7714066A priority patent/NL7714066A/xx

1978-10-16 Priority to ES474234A priority patent/ES474234A1/es

1978-10-16 Priority to ES474233A priority patent/ES474233A1/es

1979-05-17 Priority to US06/039,752 priority patent/US4284634A/en

1979-07-13 Priority to AR277301A priority patent/AR221887A1/es

1980-05-21 Priority to AT272280A priority patent/AT367402B/de

1980-08-25 Priority to US06/180,905 priority patent/US4338322A/en

1980-12-04 Priority to US06/213,048 priority patent/US4370334A/en

1981-06-10 Publication of GB1591089A publication Critical patent/GB1591089A/en

1982-04-16 Priority to DK172182A priority patent/DK172182A/da

1982-07-13 Priority to SE8204312A priority patent/SE8204312L/sv

1982-09-03 Priority to US06/414,842 priority patent/US4525478A/en

1982-10-29 Priority to CH632682A priority patent/CH638785A5/de

Status Expired legal-status Critical Current

Links

YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical class C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 title abstract description 12
238000000034 method Methods 0.000 title description 40
238000002360 preparation method Methods 0.000 title description 6
150000001875 compounds Chemical class 0.000 claims abstract description 107
125000000217 alkyl group Chemical group 0.000 claims abstract description 86
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 70
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 43
125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 22
150000003839 salts Chemical class 0.000 claims abstract description 13
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 6
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims abstract description 5
-1 hydroxy, hydroxyimino Chemical group 0.000 claims description 173
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 135
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 126
239000000203 mixture Substances 0.000 claims description 101
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 100
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 65
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 claims description 55
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 53
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 50
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 48
239000013078 crystal Substances 0.000 claims description 46
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 43
239000011541 reaction mixture Substances 0.000 claims description 43
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 39
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 32
239000003921 oil Substances 0.000 claims description 30
229910052943 magnesium sulfate Inorganic materials 0.000 claims description 25
235000019341 magnesium sulphate Nutrition 0.000 claims description 25
238000003756 stirring Methods 0.000 claims description 25
125000003545 alkoxy group Chemical group 0.000 claims description 20
125000001589 carboacyl group Chemical group 0.000 claims description 20
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
XMVJITFPVVRMHC-UHFFFAOYSA-N roxarsone Chemical group OC1=CC=C([As](O)(O)=O)C=C1[N+]([O-])=O XMVJITFPVVRMHC-UHFFFAOYSA-N 0.000 claims description 19
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 18
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 16
125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 claims description 16
229910000033 sodium borohydride Inorganic materials 0.000 claims description 16
239000012279 sodium borohydride Substances 0.000 claims description 16
238000001953 recrystallisation Methods 0.000 claims description 13
239000002904 solvent Substances 0.000 claims description 13
125000001424 substituent group Chemical group 0.000 claims description 13
125000004423 acyloxy group Chemical group 0.000 claims description 12
125000005530 alkylenedioxy group Chemical group 0.000 claims description 12
239000000284 extract Substances 0.000 claims description 11
239000012452 mother liquor Substances 0.000 claims description 11
239000000843 powder Substances 0.000 claims description 9
239000000706 filtrate Substances 0.000 claims description 8
239000000725 suspension Substances 0.000 claims description 8
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
239000011369 resultant mixture Substances 0.000 claims description 6
239000012024 dehydrating agents‎ Substances 0.000 claims description 5
239000007787 solid Substances 0.000 claims description 5
239000003795 chemical substances by application Substances 0.000 claims description 4
239000012265 solid product Substances 0.000 claims description 4
239000000126 substance Substances 0.000 claims description 4
UMBSMQALQQULTK-UHFFFAOYSA-N 3-o-ethyl 5-o-(2-phenylmethoxyethyl) 2-formyl-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C=O)NC(C)=C(C(=O)OCCOCC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 UMBSMQALQQULTK-UHFFFAOYSA-N 0.000 claims description 3
239000003638 chemical reducing agent Substances 0.000 claims description 3
238000001704 evaporation Methods 0.000 claims description 3
230000003301 hydrolyzing effect Effects 0.000 claims description 3
YCKAGGHNUHZKCL-UHFFFAOYSA-N propan-2-yl 3-aminobut-2-enoate Chemical compound CC(C)OC(=O)C=C(C)N YCKAGGHNUHZKCL-UHFFFAOYSA-N 0.000 claims description 3
QUEHTJCHIQKEIB-UHFFFAOYSA-N 5-ethoxycarbonyl-6-(hydroxymethyl)-2-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid Chemical compound CCOC(=O)C1=C(CO)NC(C)=C(C(O)=O)C1C1=CC=CC([N+]([O-])=O)=C1 QUEHTJCHIQKEIB-UHFFFAOYSA-N 0.000 claims description 2
XWKGWWGBIFAJOG-UHFFFAOYSA-N dimethyl 2-(hydroxymethyl)-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(CO)=C(C(=O)OC)C1C1=CC=CC([N+]([O-])=O)=C1 XWKGWWGBIFAJOG-UHFFFAOYSA-N 0.000 claims description 2
XLQZAXDBGNMWEK-UHFFFAOYSA-N methyl 2-[2-(1,3-dioxolane-2-carbonyl)-3-methoxy-3-oxoprop-1-enyl]benzoate Chemical compound COC(=O)C1=C(C=C(C(=O)OC)C(=O)C2OCCO2)C=CC=C1 XLQZAXDBGNMWEK-UHFFFAOYSA-N 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
238000004519 manufacturing process Methods 0.000 claims 1
238000006243 chemical reaction Methods 0.000 abstract description 27
208000024172 Cardiovascular disease Diseases 0.000 abstract description 3
206010020772 Hypertension Diseases 0.000 abstract description 3
230000000304 vasodilatating effect Effects 0.000 abstract description 3
LLXMXDARGVXTPP-UHFFFAOYSA-N 2-methyl-1,4-dihydropyridine Chemical class CC1=CCC=CN1 LLXMXDARGVXTPP-UHFFFAOYSA-N 0.000 abstract 1
230000001077 hypotensive effect Effects 0.000 abstract 1
239000000825 pharmaceutical preparation Substances 0.000 abstract 1
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 117
239000000243 solution Substances 0.000 description 59
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 50
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 48
235000019198 oils Nutrition 0.000 description 28
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 26
229910000030 sodium bicarbonate Inorganic materials 0.000 description 25
235000017557 sodium bicarbonate Nutrition 0.000 description 25
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 24
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 14
238000001816 cooling Methods 0.000 description 14
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
239000000741 silica gel Substances 0.000 description 13
229910002027 silica gel Inorganic materials 0.000 description 13
229960001866 silicon dioxide Drugs 0.000 description 13
239000011780 sodium chloride Substances 0.000 description 13
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
238000001914 filtration Methods 0.000 description 11
238000010992 reflux Methods 0.000 description 11
229920006395 saturated elastomer Polymers 0.000 description 11
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
125000004356 hydroxy functional group Chemical group O* 0.000 description 8
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
239000000047 product Substances 0.000 description 7
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
239000002253 acid Substances 0.000 description 6
150000001335 aliphatic alkanes Chemical group 0.000 description 6
239000007864 aqueous solution Substances 0.000 description 6
230000007062 hydrolysis Effects 0.000 description 6
238000006460 hydrolysis reaction Methods 0.000 description 6
PJYQRBMGZRVNSQ-UHFFFAOYSA-N methyl 4,4-dimethoxy-3-oxobutanoate Chemical compound COC(OC)C(=O)CC(=O)OC PJYQRBMGZRVNSQ-UHFFFAOYSA-N 0.000 description 6
239000012044 organic layer Substances 0.000 description 6
239000002244 precipitate Substances 0.000 description 6
239000001632 sodium acetate Substances 0.000 description 6
235000017281 sodium acetate Nutrition 0.000 description 6
239000007858 starting material Substances 0.000 description 6
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
125000004432 carbon atom Chemical group C* 0.000 description 5
230000018044 dehydration Effects 0.000 description 5
238000006297 dehydration reaction Methods 0.000 description 5
238000006722 reduction reaction Methods 0.000 description 5
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 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
229910021529 ammonia Inorganic materials 0.000 description 4
FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 4
238000004440 column chromatography Methods 0.000 description 4
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
235000019253 formic acid Nutrition 0.000 description 4
XKORCTIIRYKLLG-ARJAWSKDSA-N methyl (z)-3-aminobut-2-enoate Chemical compound COC(=O)\C=C(\C)N XKORCTIIRYKLLG-ARJAWSKDSA-N 0.000 description 4
230000003287 optical effect Effects 0.000 description 4
150000007524 organic acids Chemical class 0.000 description 4
238000000746 purification Methods 0.000 description 4
150000003254 radicals Chemical class 0.000 description 4
229910052702 rhenium Inorganic materials 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
239000007853 buffer solution Substances 0.000 description 3
OCFGILYPZQFBTO-UHFFFAOYSA-N diethyl 2-formyl-4-(2-methoxycarbonylphenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C=O)=C(C(=O)OCC)C1C1=CC=CC=C1C(=O)OC OCFGILYPZQFBTO-UHFFFAOYSA-N 0.000 description 3
239000002024 ethyl acetate extract Substances 0.000 description 3
239000008187 granular material Substances 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
239000010410 layer Substances 0.000 description 3
239000007788 liquid Substances 0.000 description 3
AIAYYSDLZSJGCY-UHFFFAOYSA-N methyl 4,4-dimethoxy-2-[(2-nitrophenyl)methylidene]-3-oxobutanoate Chemical compound COC(OC)C(=O)C(C(=O)OC)=CC1=CC=CC=C1[N+]([O-])=O AIAYYSDLZSJGCY-UHFFFAOYSA-N 0.000 description 3
150000007522 mineralic acids Chemical class 0.000 description 3
125000004043 oxo group Chemical group O=* 0.000 description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
COLPLFZHPXIFCQ-UHFFFAOYSA-N 1,4-dihydropyridine-3,5-dicarboxylic acid Chemical compound OC(=O)C1=CNC=C(C(O)=O)C1 COLPLFZHPXIFCQ-UHFFFAOYSA-N 0.000 description 2
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 2
CMWKITSNTDAEDT-UHFFFAOYSA-N 2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC=C1C=O CMWKITSNTDAEDT-UHFFFAOYSA-N 0.000 description 2
ZETIVVHRRQLWFW-UHFFFAOYSA-N 3-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC(C=O)=C1 ZETIVVHRRQLWFW-UHFFFAOYSA-N 0.000 description 2
QDAVBPXYCQLOTC-UHFFFAOYSA-N 3-o-methyl 5-o-propan-2-yl 2-formyl-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C=O)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC=C1[N+]([O-])=O QDAVBPXYCQLOTC-UHFFFAOYSA-N 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 2
229940126062 Compound A Drugs 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
238000005903 acid hydrolysis reaction Methods 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
150000001299 aldehydes Chemical class 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
125000003282 alkyl amino group Chemical group 0.000 description 2
150000003863 ammonium salts Chemical class 0.000 description 2
239000002585 base Substances 0.000 description 2
230000017531 blood circulation Effects 0.000 description 2
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 2
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125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
239000000463 material Substances 0.000 description 1
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
RPNNPZHFJPXFQS-UHFFFAOYSA-N methane;rhodium Chemical compound C.[Rh] RPNNPZHFJPXFQS-UHFFFAOYSA-N 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
XCWQQAFTYWSAAI-UHFFFAOYSA-N methyl 2-(4,4-diethoxy-2-ethoxycarbonyl-3-oxobut-1-enyl)benzoate Chemical compound CCOC(OCC)C(=O)C(C(=O)OCC)=CC1=CC=CC=C1C(=O)OC XCWQQAFTYWSAAI-UHFFFAOYSA-N 0.000 description 1
YRMODRRGEUGHTF-UHFFFAOYSA-N methyl 2-formylbenzoate Chemical compound COC(=O)C1=CC=CC=C1C=O YRMODRRGEUGHTF-UHFFFAOYSA-N 0.000 description 1
WJMUEQYQRJJCRC-UHFFFAOYSA-N methyl 4,4-dimethoxy-2-[(3-nitrophenyl)methylidene]-3-oxobutanoate Chemical compound COC(OC)C(=O)C(C(=O)OC)=CC1=CC=CC([N+]([O-])=O)=C1 WJMUEQYQRJJCRC-UHFFFAOYSA-N 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
IGJZFKODGSWBBQ-UHFFFAOYSA-N n,n,2-trimethylbenzenesulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=CC=C1C IGJZFKODGSWBBQ-UHFFFAOYSA-N 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
229960001597 nifedipine Drugs 0.000 description 1
HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
229960001412 pentobarbital Drugs 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
239000008024 pharmaceutical diluent Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
125000006678 phenoxycarbonyl group Chemical group 0.000 description 1
AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
CMPQUABWPXYYSH-UHFFFAOYSA-N phenyl phosphate Chemical compound OP(O)(=O)OC1=CC=CC=C1 CMPQUABWPXYYSH-UHFFFAOYSA-N 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([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
LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
239000000376 reactant Substances 0.000 description 1
229910052701 rubidium Inorganic materials 0.000 description 1
230000007017 scission Effects 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
239000005049 silicon tetrachloride Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000000454 talc Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000000844 transformation Methods 0.000 description 1
PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 description 1
DQWPFSLDHJDLRL-UHFFFAOYSA-N triethyl phosphate Chemical compound CCOP(=O)(OCC)OCC DQWPFSLDHJDLRL-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1
238000010792 warming Methods 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- 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
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
- C07C205/56—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups bound to carbon atoms of six-membered aromatic rings and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Hydrogenated Pyridines (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

GB52720/76A 1975-07-02 1976-12-17 1,4-dihydropyridine derivatives and process for preparation thereof Expired GB1591089A (en)

Priority Applications (28)

Application Number	Priority Date	Filing Date	Title
CA256,210A CA1080223A (en)	1975-07-02	1976-07-02	1,4-dihydropyridine derivatives, process for preparation thereof and pharmaceutical composition of the same
GB52720/76A GB1591089A (en)	1976-12-17	1976-12-17	1,4-dihydropyridine derivatives and process for preparation thereof
MX689277U MX5273E (es)	1976-12-17	1977-12-15	Procedimiento para preparar derivados de la 4-fenil-1,4-dihidropiridina
AR270392A AR221478A1 (es)	1976-12-17	1977-12-16	Procedimiento para preparar compuestos de 4-fenil 6-hidroxialquil(c1-c4)-1,4-dihidropirimidinas y sus sales
HU77FU358A HU176454B (en)	1976-12-17	1977-12-16	Process for preparing 1,4-dihydro-pyridine derivatives
JP52152290A JPS5948828B2 (ja)	1976-12-17	1977-12-16	１．４↓−ジヒドロピリジン化合物およびその製造法
BE183553A BE861964A (fr)	1976-12-17	1977-12-16	Derives de la 1,4-dihydropyridine, leur procede d'obtention et composition pharmaceutique les contenant
DE19772756226 DE2756226A1 (de)	1976-12-17	1977-12-16	1,4-dihydropyridin-verbindungen, verfahren zu ihrer herstellung und sie enthaltende pharmazeutische mittel
ES465137A ES465137A1 (es)	1976-12-17	1977-12-16	Un procedimiento para preparar compuestos de 6-hidroxialco- hil-1,4-dihidropiridina
FR7738126A FR2374307A1 (fr)	1976-12-17	1977-12-16	Derives de la 1,4-dihydropyridine, leur procede d'obtention et composition pharmaceutique les contenant
DK563377A DK563377A (da)	1976-12-17	1977-12-16	R fremgangsmaade til fremstilling af 1,4-dihydropyridinderivate
CH1553477A CH633266A5 (en)	1976-12-17	1977-12-16	Process for preparing 1,4-dihydropyridine compounds
AU31657/77A AU518206B2 (en)	1976-12-17	1977-12-16	Derivatives of 4-phenyl 1, 4-dihydropyridine-3, 5-dicarboxylate
SE7714374A SE7714374L (sv)	1976-12-17	1977-12-16	1,4-dihydropyridinforbindelser
AT0901877A AT367401B (de)	1976-12-17	1977-12-16	Verfahren zur herstellung von neuen 6-hydroxyalkyl-1,4-dihydropyridinverbindungen
NL7714066A NL7714066A (nl)	1976-12-17	1977-12-19	1.4-dihydropyridineverbindingen, werkwijze voor de bereiding daarvan en farmaceutische prepara- ten, die deze verbindingen bevatten.
ZA00777532A ZA777532B (en)	1976-12-17	1977-12-19	1,4-dihydropyridine compounds,process for preparation thereof and pharmaceutical composition of the same
ES474234A ES474234A1 (es)	1976-12-17	1978-10-16	Un procedimiento para preparar compuestos de 1,4-dihidropi- ridina sustituidos en posicion 6
ES474233A ES474233A1 (es)	1976-12-17	1978-10-16	Un procedimiento para preparar compuestos de 1,4-dihidropi- ridina
US06/039,752 US4284634A (en)	1975-07-02	1979-05-17	1,4-Dihydropyridine derivatives, and pharmaceutical method of the same
AR277301A AR221887A1 (es)	1976-12-17	1979-07-13	Procedimiento para preparar compuestos de 6-ciano-4-4-fenil-2-alquil(c1-c4)1,4-dihidropiridinas
AT272280A AT367402B (de)	1976-12-17	1980-05-21	Verfahren zur herstellung von neuen 1,4dihydropyridinverbindungen
US06/180,905 US4338322A (en)	1975-07-02	1980-08-25	1,4-Dihydropyridine derivatives, pharmaceutical compositions containing same and methods of effecting vasodilation using same
US06/213,048 US4370334A (en)	1975-07-02	1980-12-04	1,4-Dihydro-pyridine derivatives and methods of using same
DK172182A DK172182A (da)	1976-12-17	1982-04-16	Fremgangsmaade til fremstilling af 1,4-dihydropyridinderivater
SE8204312A SE8204312L (sv)	1976-12-17	1982-07-13	Forfarande for framstellning av 1,4-dihydropyridinderivat
US06/414,842 US4525478A (en)	1975-07-02	1982-09-03	Certain 4-aryl-1,4-dihydro-3,5-pyridinedicarboxylates having vasodilating and anti-hypertensive properties
CH632682A CH638785A5 (en)	1976-12-17	1982-10-29	Process for the preparation of 1,4-dihydropyridine compounds

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GB52720/76A GB1591089A (en)	1976-12-17	1976-12-17	1,4-dihydropyridine derivatives and process for preparation thereof

Publications (1)

Publication Number	Publication Date
GB1591089A true GB1591089A (en)	1981-06-10

Family

ID=10465031

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
GB52720/76A Expired GB1591089A (en)	1975-07-02	1976-12-17	1,4-dihydropyridine derivatives and process for preparation thereof

Country Status (15)

Country	Link
JP (1)	JPS5948828B2 (es)
AR (2)	AR221478A1 (es)
AT (1)	AT367401B (es)
AU (1)	AU518206B2 (es)
BE (1)	BE861964A (es)
CH (1)	CH633266A5 (es)
DE (1)	DE2756226A1 (es)
DK (2)	DK563377A (es)
ES (3)	ES465137A1 (es)
FR (1)	FR2374307A1 (es)
GB (1)	GB1591089A (es)
HU (1)	HU176454B (es)
NL (1)	NL7714066A (es)
SE (2)	SE7714374L (es)
ZA (1)	ZA777532B (es)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0080220A1 (en) *	1981-11-17	1983-06-01	FISONS plc	Dihydropyridines, methods for their production and their formulation and use as pharmaceuticals
EP0101023A1 (en) *	1982-08-06	1984-02-22	Banyu Pharmaceutical Co., Ltd.	Process for preparing 2-carbamoyloxyalkyl-1,4-dihydropyridine derivatives and intermediates useful for the process
GB2196631A (en) *	1986-10-31	1988-05-05	Nippon Shinyaku Co Ltd	2-substituted 1,4-dihydropyridine derivatives
US5977369A (en) *	1995-12-28	1999-11-02	Napp Technologies, Inc.	Process to prepare dihydropyridine and derivatives thereof
CN101987833A (zh) *	2009-08-04	2011-03-23	北京利乐生制药科技有限公司	尼伐地平新晶型及其制备方法
CN103254122A (zh) *	2013-06-19	2013-08-21	湖南师范大学	一种心血管药物尼伐地平的制备方法

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4307103A (en) *	1978-09-08	1981-12-22	Fujisawa Pharmaceutical Co., Ltd.	Dihydropyridine derivative, processes for preparation thereof and pharmaceutical composition comprising the same
CA1117117A (en) *	1978-10-10	1982-01-26	Fujisawa Pharmaceutical Co., Ltd.	2-methyl-dihydropyridine compound, processes for preparation thereof and pharmaceutical composition comprising the same
DE2935451A1 (de) *	1979-09-01	1981-03-19	Bayer Ag, 5090 Leverkusen	Optisch aktive 1,4-dihydropyridine, verfahren zu ihrer herstellung und ihre verwendung als arneimittel
DE3018259A1 (de) *	1980-05-13	1981-11-19	Bayer Ag, 5090 Leverkusen	1,4-dihydropyridine mit unterschiedlichen substituenten in 2- und 6-position, verfahren zu ihrer herstellung und ihre verwendung in arzneimitteln
JPS57175164A (en) *	1981-04-18	1982-10-28	Banyu Pharmaceut Co Ltd	1,4-dihydropyridine derivative and its preparation
ZA83959B (en) *	1982-03-10	1984-09-26	Sandoz Ltd	1,4-dihydropyridine derivatives,their preparation and pharmaceutical compositions containing them
GB8412208D0 (en) *	1984-05-12	1984-06-20	Pfizer Ltd	Quinolone inotropic agents
US4678796A (en) *	1984-11-30	1987-07-07	Warner-Lambert Company	2-alkylidene derivatives of 1,2,3,4-tetrahydropyridine-2,5-pyridine carboxylic acid dialkyl esters useful for treatment of cardiovascular disorders
FI862343A7 (fi)	1985-06-17	1986-12-18	Warner Lambert Co	Foerfarande foer framstaellning av terapeutiskt verkande 1,4-dihydropyridinfoereningar.
DE3675747D1 (de) *	1985-08-21	1991-01-03	Glaxo Spa	1,4-dihydropyridinverbindungen und ihre herstellung und pharmazeutische formulierung.
DE3544211A1 (de) *	1985-12-13	1987-06-19	Bayer Ag	Neue, fluorhaltige 1,4-dihydropyridine, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel
IT1204460B (it) *	1986-02-20	1989-03-01	Glaxo Spa	Derivati eterociclici
FR2596760B1 (fr) *	1986-04-02	1988-12-09	Sori Soc Rech Ind	Derives dissymetriques de l'acide 1,4-dihydropyridine-3,5-dicarboxylique, procedes de preparation et utilisation en therapeutique
US4732898A (en) *	1986-04-29	1988-03-22	Warner-Lambert Company	2-(2-aryl-2-oxoalkylidene) analogs of-3,5-pyridinedicarboxylic acid dialkyl esters useful for treatment of cardiovascular disorders

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE1963188A1 (de) *	1969-12-17	1971-06-24	Bayer Ag	Neue Cyanphenyl-1,4-dihydropyridinderivate
DE2248150A1 (de) *	1972-09-30	1974-04-04	Bayer Ag	Dihydropyridinpolyester, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel
US3946027A (en) *	1972-09-30	1976-03-23	Bayer Aktiengesellschaft	3,5,6-Tricarboxy-4-pyridyl-1,4-dihydropyridine derivatives
US3946028A (en) *	1972-09-30	1976-03-23	Bayer Aktiengesellschaft	2,3,5,6-Tetracarboxy-4-pyridyl-1,4-dihydropyridine derivatives
DE2335466A1 (de) *	1973-07-12	1975-01-30	Bayer Ag	Alkoxyalkyl-1,4-dihydropyridine, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel
CH607848A5 (es) *	1974-06-04	1978-11-30	Bayer Ag
GB1552911A (en) *	1975-07-02	1979-09-19	Fujisawa Pharmaceutical Co	1,4 dihydropyridine derivatives and the preparation thereof

1976
- 1976-12-17 GB GB52720/76A patent/GB1591089A/en not_active Expired
1977
- 1977-12-16 ES ES465137A patent/ES465137A1/es not_active Expired
- 1977-12-16 AT AT0901877A patent/AT367401B/de not_active IP Right Cessation
- 1977-12-16 AU AU31657/77A patent/AU518206B2/en not_active Expired
- 1977-12-16 CH CH1553477A patent/CH633266A5/de not_active IP Right Cessation
- 1977-12-16 DE DE19772756226 patent/DE2756226A1/de not_active Ceased
- 1977-12-16 FR FR7738126A patent/FR2374307A1/fr active Granted
- 1977-12-16 HU HU77FU358A patent/HU176454B/hu unknown
- 1977-12-16 JP JP52152290A patent/JPS5948828B2/ja not_active Expired
- 1977-12-16 SE SE7714374A patent/SE7714374L/xx not_active Application Discontinuation
- 1977-12-16 AR AR270392A patent/AR221478A1/es active
- 1977-12-16 BE BE183553A patent/BE861964A/xx not_active IP Right Cessation
- 1977-12-16 DK DK563377A patent/DK563377A/da not_active Application Discontinuation
- 1977-12-19 NL NL7714066A patent/NL7714066A/xx not_active Application Discontinuation
- 1977-12-19 ZA ZA00777532A patent/ZA777532B/xx unknown
1978
- 1978-10-16 ES ES474234A patent/ES474234A1/es not_active Expired
- 1978-10-16 ES ES474233A patent/ES474233A1/es not_active Expired
1979
- 1979-07-13 AR AR277301A patent/AR221887A1/es active
1982
- 1982-04-16 DK DK172182A patent/DK172182A/da active IP Right Grant
- 1982-07-13 SE SE8204312A patent/SE8204312L/sv not_active Application Discontinuation

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0080220A1 (en) *	1981-11-17	1983-06-01	FISONS plc	Dihydropyridines, methods for their production and their formulation and use as pharmaceuticals
EP0101023A1 (en) *	1982-08-06	1984-02-22	Banyu Pharmaceutical Co., Ltd.	Process for preparing 2-carbamoyloxyalkyl-1,4-dihydropyridine derivatives and intermediates useful for the process
GB2196631A (en) *	1986-10-31	1988-05-05	Nippon Shinyaku Co Ltd	2-substituted 1,4-dihydropyridine derivatives
GB2196631B (en) *	1986-10-31	1990-07-11	Nippon Shinyaku Co Ltd	2-substituted 1,4-dihydropyridine derivatives
US5977369A (en) *	1995-12-28	1999-11-02	Napp Technologies, Inc.	Process to prepare dihydropyridine and derivatives thereof
CN101987833A (zh) *	2009-08-04	2011-03-23	北京利乐生制药科技有限公司	尼伐地平新晶型及其制备方法
CN103951608A (zh) *	2009-08-04	2014-07-30	北京利乐生制药科技有限公司	尼伐地平晶型及其制备方法
CN101987833B (zh) *	2009-08-04	2014-07-30	北京利乐生制药科技有限公司	尼伐地平晶型及其制备方法
CN103951608B (zh) *	2009-08-04	2016-04-27	喜德生（苏州）医药科技有限公司	尼伐地平晶型及其制备方法
CN103254122A (zh) *	2013-06-19	2013-08-21	湖南师范大学	一种心血管药物尼伐地平的制备方法

Also Published As

Publication number	Publication date
ES474233A1 (es)	1979-11-01
DK172182A (da)	1982-04-16
FR2374307B1 (es)	1981-02-13
NL7714066A (nl)	1978-06-20
SE7714374L (sv)	1978-06-18
AR221478A1 (es)	1981-02-13
CH633266A5 (en)	1982-11-30
ATA901877A (de)	1981-11-15
AR221887A1 (es)	1981-03-31
JPS5395977A (en)	1978-08-22
AU3165777A (en)	1979-06-21
ZA777532B (en)	1978-10-25
HU176454B (en)	1981-03-28
JPS5948828B2 (ja)	1984-11-29
ES474234A1 (es)	1979-04-01
AT367401B (de)	1982-07-12
DK563377A (da)	1978-06-18
FR2374307A1 (fr)	1978-07-13
AU518206B2 (en)	1981-09-17
BE861964A (fr)	1978-06-16
DE2756226A1 (de)	1978-06-29
SE8204312D0 (sv)	1982-07-13
ES465137A1 (es)	1979-01-01
SE8204312L (sv)	1982-07-13

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GB1591089A (en)	1981-06-10	1,4-dihydropyridine derivatives and process for preparation thereof
CH634052A5 (de)	1983-01-14	Verfahren zur herstellung neuer 1,4-dihydropyridinderivate.
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AU777565B2 (en)	2004-10-21	Process for preparing amlodipine benzenesulphonate
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HU193085B (en)	1987-08-28	Process for production of spergualin derivatives consosting of new phenilene group and for production of medical preparatives consisting of such compounds
KR100878739B1 (ko)	2009-01-14	발기부전 치료를 위한 신규한 화합물
IL116384A (en)	1996-10-16	Ylidene compounds and their preparation
JP3221874B2 (ja)	2001-10-22	クラウセンアミドおよびネオクラウセンアミド並びにそれらの誘導体の製法
US4575553A (en)	1986-03-11	Antitumor m-AMSA analog
EP0093945A2 (en)	1983-11-16	1,4-Dihydropyridine derivatives
HU193785B (en)	1987-11-30	Process for producing dihydropyridine derivatives
EP0063359B1 (en)	1985-12-11	1,4-dihydropyridine derivatives and processes for preparing the same
ES2912409T3 (es)	2022-05-25	Intermedios y procesos para la preparación de linagliptina y sus sales
EP0292981B1 (en)	1991-04-17	2-selenomethyl-1, 4-dihydropyridines, a process for the preparation thereof and pharmaceutical compositions containing them
US4622329A (en)	1986-11-11	1-cyclohexyl-3,4-dihydroisoquinoline derivatives and pharmaceutical compositions containing them
RU2155752C2 (ru)	2000-09-10	Способы получения производных 1,4-дигидропиридин-3,5-дикарбоновой кислоты в виде r-изомеров и их солей, исходные и промежуточные продукты для их получения
HU193786B (en)	1987-11-30	Process for producing dihydropyridine derivatives
EP0079740B1 (en)	1985-11-13	Anthraniloyloxyalkanoates
CA1080223A (en)	1980-06-24	1,4-dihydropyridine derivatives, process for preparation thereof and pharmaceutical composition of the same
KR800001593B1 (ko)	1980-12-29	1, 4-디하이드로 피리딘 유도체의 제조방법
KR800001592B1 (ko)	1980-12-29	1, 4-디하이드로피리딘 유도체의 제조방법

Legal Events

Date	Code	Title	Description
1981-08-26	PS	Patent sealed
1989-08-09	PCNP	Patent ceased through non-payment of renewal fee