CH633266A5 - Process for preparing 1,4-dihydropyridine compounds - Google Patents

Process for preparing 1,4-dihydropyridine compounds Download PDF

Info

Publication number: CH633266A5
Authority: CH; Switzerland
Prior art keywords: methyl; acid; dihydropyridine; mixture; compound
Prior art date: 1976-12-17

Application number

CH1553477A

Other languages

German (de)

English (en)

Inventor

Yoshinari Sato

Original Assignee

Fujisawa Pharmaceutical Co

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

1977-12-16

Publication date

1982-11-30

1977-12-16 Application filed by Fujisawa Pharmaceutical Co filed Critical Fujisawa Pharmaceutical Co

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

1982-11-30 Publication of CH633266A5 publication Critical patent/CH633266A5/de

Links

YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical class C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 title claims description 12
238000004519 manufacturing process Methods 0.000 title description 2
-1 t-butoxycarbonyl Chemical group 0.000 claims description 95
238000000034 method Methods 0.000 claims description 37
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 31
150000001875 compounds Chemical class 0.000 claims description 29
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 16
238000002360 preparation method Methods 0.000 claims description 10
150000003839 salts Chemical class 0.000 claims description 9
125000000217 alkyl group Chemical group 0.000 claims description 7
239000003795 chemical substances by application Substances 0.000 claims description 7
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
125000004742 propyloxycarbonyl group Chemical group 0.000 claims description 4
125000004744 butyloxycarbonyl group Chemical group 0.000 claims description 3
125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 claims description 3
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 3
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 2
125000004093 cyano group Chemical group *C#N 0.000 claims 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 claims 1
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 64
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 54
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
239000000203 mixture Substances 0.000 description 47
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
239000000243 solution Substances 0.000 description 29
238000006243 chemical reaction Methods 0.000 description 23
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 23
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 21
239000011541 reaction mixture Substances 0.000 description 21
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 19
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
101150041968 CDC13 gene Proteins 0.000 description 17
239000002253 acid Substances 0.000 description 16
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
239000002904 solvent Substances 0.000 description 15
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 12
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
239000013078 crystal Substances 0.000 description 11
239000000843 powder Substances 0.000 description 11
229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
235000017557 sodium bicarbonate Nutrition 0.000 description 11
238000003756 stirring Methods 0.000 description 11
238000001816 cooling Methods 0.000 description 10
239000003921 oil Substances 0.000 description 10
235000019198 oils Nutrition 0.000 description 10
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
229910052943 magnesium sulfate Inorganic materials 0.000 description 9
235000019341 magnesium sulphate Nutrition 0.000 description 9
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
230000007062 hydrolysis Effects 0.000 description 8
238000006460 hydrolysis reaction Methods 0.000 description 8
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 7
125000003545 alkoxy group Chemical group 0.000 description 7
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
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
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
238000010438 heat treatment Methods 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
239000000725 suspension 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
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
125000004423 acyloxy group Chemical group 0.000 description 5
125000005530 alkylenedioxy group Chemical group 0.000 description 5
239000000047 product Substances 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
239000011780 sodium chloride Substances 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
206010020772 Hypertension Diseases 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
150000001299 aldehydes Chemical class 0.000 description 4
125000004849 alkoxymethyl group Chemical group 0.000 description 4
235000019253 formic acid Nutrition 0.000 description 4
BDDWJQDFRYGGQU-UHFFFAOYSA-N methyl 2-[(2-cyanophenyl)methylidene]-4,4-dimethoxy-3-oxobutanoate Chemical compound COC(OC)C(=O)C(C(=O)OC)=CC1=CC=CC=C1C#N BDDWJQDFRYGGQU-UHFFFAOYSA-N 0.000 description 4
229910052757 nitrogen Inorganic materials 0.000 description 4
230000003287 optical effect Effects 0.000 description 4
150000007524 organic acids Chemical class 0.000 description 4
239000012044 organic layer Substances 0.000 description 4
239000007787 solid Substances 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
UTTMGHVREFQRCU-UHFFFAOYSA-N 4-(2-cyanophenyl)-5-ethoxycarbonyl-6-formyl-2-methyl-1,4-dihydropyridine-3-carboxylic acid Chemical compound CCOC(=O)C1=C(C=O)NC(C)=C(C(O)=O)C1C1=CC=CC=C1C#N UTTMGHVREFQRCU-UHFFFAOYSA-N 0.000 description 3
SEWLVYNVABKCCO-UHFFFAOYSA-N 4-(2-cyanophenyl)-6-(diethoxymethyl)-5-ethoxycarbonyl-2-methyl-1,4-dihydropyridine-3-carboxylic acid Chemical compound OC(=O)C1=C(C)NC(C(OCC)OCC)=C(C(=O)OCC)C1C1=CC=CC=C1C#N SEWLVYNVABKCCO-UHFFFAOYSA-N 0.000 description 3
208000024172 Cardiovascular disease Diseases 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
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
150000004729 acetoacetic acid derivatives Chemical class 0.000 description 3
150000001335 aliphatic alkanes Chemical group 0.000 description 3
229910021529 ammonia Inorganic materials 0.000 description 3
239000007853 buffer solution Substances 0.000 description 3
239000012024 dehydrating agents‎ Substances 0.000 description 3
238000001914 filtration Methods 0.000 description 3
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
239000007788 liquid Substances 0.000 description 3
150000007522 mineralic acids Chemical class 0.000 description 3
239000012452 mother liquor Substances 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
238000010992 reflux Methods 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
QVTPWONEVZJCCS-UHFFFAOYSA-N 2-formylbenzonitrile Chemical compound O=CC1=CC=CC=C1C#N QVTPWONEVZJCCS-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
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
206010002383 Angina Pectoris Diseases 0.000 description 2
229940126062 Compound A Drugs 0.000 description 2
206010052895 Coronary artery insufficiency Diseases 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-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
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-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
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 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
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 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
238000009835 boiling Methods 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
125000004432 carbon atom Chemical group C* 0.000 description 2
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
239000012043 crude product Substances 0.000 description 2
JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 2
VSNQXUISKZQCIM-UHFFFAOYSA-N diethyl 2-(diethoxymethyl)-4-(2-methoxycarbonylphenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C(OCC)OCC)=C(C(=O)OCC)C1C1=CC=CC=C1C(=O)OC VSNQXUISKZQCIM-UHFFFAOYSA-N 0.000 description 2
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
BOTWXBGGKSWUDP-UHFFFAOYSA-N dimethyl 4-(2-cyanophenyl)-2-(dimethoxymethyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C(OC)OC)=C(C(=O)OC)C1C1=CC=CC=C1C#N BOTWXBGGKSWUDP-UHFFFAOYSA-N 0.000 description 2
238000004821 distillation Methods 0.000 description 2
239000003814 drug Substances 0.000 description 2
239000002024 ethyl acetate extract Substances 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
239000000284 extract Substances 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
239000010410 layer Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
239000000463 material Substances 0.000 description 2
NZTCVGHPDWAALP-UHFFFAOYSA-N methyl 2,2-dimethoxyacetate Chemical compound COC(OC)C(=O)OC NZTCVGHPDWAALP-UHFFFAOYSA-N 0.000 description 2
PJYQRBMGZRVNSQ-UHFFFAOYSA-N methyl 4,4-dimethoxy-3-oxobutanoate Chemical compound COC(OC)C(=O)CC(=O)OC PJYQRBMGZRVNSQ-UHFFFAOYSA-N 0.000 description 2
208000010125 myocardial infarction Diseases 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
229920000137 polyphosphoric acid Polymers 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
238000000746 purification Methods 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
125000001424 substituent group Chemical group 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 2
230000000304 vasodilatating effect Effects 0.000 description 2
238000005406 washing Methods 0.000 description 2
MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
DGLFDUYUBFYJJK-UHFFFAOYSA-N 1,2-dihydropyridine-4-carboxylic acid Chemical compound OC(=O)C1=CCNC=C1 DGLFDUYUBFYJJK-UHFFFAOYSA-N 0.000 description 1
NOGFHTGYPKWWRX-UHFFFAOYSA-N 2,2,6,6-tetramethyloxan-4-one Chemical compound CC1(C)CC(=O)CC(C)(C)O1 NOGFHTGYPKWWRX-UHFFFAOYSA-N 0.000 description 1
YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
OEWWUBFBPXIJIZ-UHFFFAOYSA-N 2-[(2-cyanophenyl)methylidene]-3-oxobutanoic acid Chemical compound C(#N)C1=C(C=C(C(=O)O)C(=O)C)C=CC=C1 OEWWUBFBPXIJIZ-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
MDHHILKUOBIENR-UHFFFAOYSA-N 4,4-dimethoxy-3-oxobutanoic acid Chemical compound COC(OC)C(=O)CC(O)=O MDHHILKUOBIENR-UHFFFAOYSA-N 0.000 description 1
XQFJICBSTXPSPF-UHFFFAOYSA-N 4-(2-cyanophenyl)-6-(dimethoxymethyl)-5-methoxycarbonyl-2-methyl-1,4-dihydropyridine-3-carboxylic acid Chemical compound OC(=O)C1=C(C)NC(C(OC)OC)=C(C(=O)OC)C1C1=CC=CC=C1C#N XQFJICBSTXPSPF-UHFFFAOYSA-N 0.000 description 1
LBYOYSGDRCXQDC-UHFFFAOYSA-N 4-(2-cyanophenyl)-6-formyl-5-methoxycarbonyl-2-methyl-1,4-dihydropyridine-3-carboxylic acid Chemical compound COC(=O)C1=C(C=O)NC(C)=C(C(O)=O)C1C1=CC=CC=C1C#N LBYOYSGDRCXQDC-UHFFFAOYSA-N 0.000 description 1
101150096316 5 gene Proteins 0.000 description 1
CFCIUCPRCZRUSG-UHFFFAOYSA-N 6-(dimethoxymethyl)-5-methoxycarbonyl-4-(2-methoxycarbonylphenyl)-2-methyl-1,4-dihydropyridine-3-carboxylic acid Chemical compound OC(=O)C1=C(C)NC(C(OC)OC)=C(C(=O)OC)C1C1=CC=CC=C1C(=O)OC CFCIUCPRCZRUSG-UHFFFAOYSA-N 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
239000005995 Aluminium silicate Substances 0.000 description 1
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
239000005695 Ammonium acetate Substances 0.000 description 1
229910015900 BF3 Inorganic materials 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
108010010803 Gelatin Proteins 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
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
XNPOFXIBHOVFFH-UHFFFAOYSA-N N-cyclohexyl-N'-(2-(4-morpholinyl)ethyl)carbodiimide Chemical compound C1CCCCC1N=C=NCCN1CCOCC1 XNPOFXIBHOVFFH-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
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 1
229910021627 Tin(IV) chloride Inorganic materials 0.000 description 1
GHVZOJONCUEWAV-UHFFFAOYSA-N [K].CCO Chemical compound [K].CCO GHVZOJONCUEWAV-UHFFFAOYSA-N 0.000 description 1
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
150000001241 acetals Chemical class 0.000 description 1
KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
239000003929 acidic solution Substances 0.000 description 1
150000008063 acylals Chemical group 0.000 description 1
125000005042 acyloxymethyl group Chemical group 0.000 description 1
239000008272 agar Substances 0.000 description 1
235000010419 agar Nutrition 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
125000003282 alkyl amino group Chemical group 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
235000012211 aluminium silicate Nutrition 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
235000019257 ammonium acetate Nutrition 0.000 description 1
229940043376 ammonium acetate Drugs 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
229910052921 ammonium sulfate Inorganic materials 0.000 description 1
235000011130 ammonium sulphate Nutrition 0.000 description 1
239000002220 antihypertensive agent Substances 0.000 description 1
229940030600 antihypertensive agent Drugs 0.000 description 1
125000005161 aryl oxy carbonyl group Chemical group 0.000 description 1
125000004104 aryloxy group Chemical group 0.000 description 1
238000010533 azeotropic distillation Methods 0.000 description 1
IBOHXZPGWRYYIA-UHFFFAOYSA-N benzene;piperidine Chemical compound C1CCNCC1.C1=CC=CC=C1 IBOHXZPGWRYYIA-UHFFFAOYSA-N 0.000 description 1
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
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 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 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
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000002775 capsule Substances 0.000 description 1
125000001589 carboacyl group Chemical group 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
150000001721 carbon Chemical group 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
239000000969 carrier Substances 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
239000003218 coronary vasodilator agent Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
230000018044 dehydration Effects 0.000 description 1
238000006297 dehydration reaction Methods 0.000 description 1
ACQKVXOILHFUFA-UHFFFAOYSA-N diethyl 2-cyano-4-(2-methoxycarbonylphenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C#N)=C(C(=O)OCC)C1C1=CC=CC=C1C(=O)OC ACQKVXOILHFUFA-UHFFFAOYSA-N 0.000 description 1
FLRFETICTIDGBS-UHFFFAOYSA-N dimethyl 4-(2-cyanophenyl)-2-(hydroxyiminomethyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C=NO)=C(C(=O)OC)C1C1=CC=CC=C1C#N FLRFETICTIDGBS-UHFFFAOYSA-N 0.000 description 1
ZWULFNOTBXXGFS-UHFFFAOYSA-N dimethyl 4-(2-cyanophenyl)-2-formyl-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C=O)=C(C(=O)OC)C1C1=CC=CC=C1C#N ZWULFNOTBXXGFS-UHFFFAOYSA-N 0.000 description 1
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
239000003480 eluent Substances 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
YGFPTOGFJZRWJR-FPLPWBNLSA-N ethyl (z)-3-amino-4,4-diethoxybut-2-enoate Chemical compound CCOC(OCC)C(\N)=C\C(=O)OCC YGFPTOGFJZRWJR-FPLPWBNLSA-N 0.000 description 1
YPMPTULBFPFSEQ-PLNGDYQASA-N ethyl (z)-3-aminobut-2-enoate Chemical compound CCOC(=O)\C=C(\C)N YPMPTULBFPFSEQ-PLNGDYQASA-N 0.000 description 1
HYVRRAANXHHPGH-UHFFFAOYSA-N ethyl 4,4-diethoxy-3-oxobutanoate Chemical compound CCOC(OCC)C(=O)CC(=O)OCC HYVRRAANXHHPGH-UHFFFAOYSA-N 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
WMYNMYVRWWCRPS-UHFFFAOYSA-N ethynoxyethane Chemical group CCOC#C WMYNMYVRWWCRPS-UHFFFAOYSA-N 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000011521 glass Substances 0.000 description 1
229940074045 glyceryl distearate Drugs 0.000 description 1
239000008187 granular material Substances 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002366 halogen compounds Chemical class 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
IBTWUVRCFHJPKN-UHFFFAOYSA-N hydron;pyridine-3-carboxylic acid;chloride Chemical compound Cl.OC(=O)C1=CC=CN=C1 IBTWUVRCFHJPKN-UHFFFAOYSA-N 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
150000002443 hydroxylamines Chemical class 0.000 description 1
230000001077 hypotensive effect Effects 0.000 description 1
239000005457 ice water Substances 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
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
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
239000000155 melt Substances 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
XKORCTIIRYKLLG-ARJAWSKDSA-N methyl (z)-3-aminobut-2-enoate Chemical compound COC(=O)\C=C(\C)N XKORCTIIRYKLLG-ARJAWSKDSA-N 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
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 description 1
YRMODRRGEUGHTF-UHFFFAOYSA-N methyl 2-formylbenzoate Chemical compound COC(=O)C1=CC=CC=C1C=O YRMODRRGEUGHTF-UHFFFAOYSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 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
239000011664 nicotinic acid Substances 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
229960001597 nifedipine Drugs 0.000 description 1
229910000069 nitrogen hydride Inorganic materials 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
150000002923 oximes Chemical class 0.000 description 1
125000004043 oxo group Chemical group O=* 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
RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 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
239000000825 pharmaceutical preparation 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
239000006187 pill 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
BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
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 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
239000000376 reactant Substances 0.000 description 1
238000007127 saponification reaction Methods 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
238000010898 silica gel chromatography Methods 0.000 description 1
ABTOQLMXBSRXSM-UHFFFAOYSA-N silicon tetrafluoride Chemical compound F[Si](F)(F)F ABTOQLMXBSRXSM-UHFFFAOYSA-N 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000003826 tablet Substances 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
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 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
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
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)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Hydrogenated Pyridines (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

CH1553477A 1976-12-17 1977-12-16 Process for preparing 1,4-dihydropyridine compounds CH633266A5 (en)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
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
CH633266A5 true CH633266A5 (en)	1982-11-30

Family

ID=10465031

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CH1553477A CH633266A5 (en)	1976-12-17	1977-12-16	Process for preparing 1,4-dihydropyridine compounds

Country Status (15)

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

Families Citing this family (20)

* 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 (fr) *	1978-10-10	1982-01-26	Fujisawa Pharmaceutical Co., Ltd.	Derives de la 2-methyl-dihydropyridine, methodes de preparation, et composition pharmaceutique de ces derives
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
DE3269219D1 (en) *	1981-11-17	1986-03-27	Fisons Plc	Dihydropyridines, methods for their production and their formulation and use as pharmaceuticals
ZA83959B (en) *	1982-03-10	1984-09-26	Sandoz Ltd	1,4-dihydropyridine derivatives,their preparation and pharmaceutical compositions containing them
HU197881B (en) *	1982-08-06	1989-06-28	Banyu Pharma Co Ltd	Process for producing new carbamoyl-oxy-alkyl-carboxy-lic acid derivatives
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
CA1267416A (fr)	1985-06-17	1990-04-03	Ila Sircar	Derives de la 1,4-dihydropyridine utiles pour le traitement de desordres cardiovasculaires
EP0226271B1 (fr) *	1985-08-21	1990-11-22	GLAXO S.p.A.	Dihydro-1,4 pyridines, leur préparation et composition pharmaceutique
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
JPS63115890A (ja) *	1986-10-31	1988-05-20	Nippon Shinyaku Co Ltd	２位置換１，４−ジヒドロピリジン誘導体
US5977369A (en) *	1995-12-28	1999-11-02	Napp Technologies, Inc.	Process to prepare dihydropyridine and derivatives thereof
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
CN103254122B (zh) *	2013-06-19	2015-04-22	湖南师范大学	一种心血管药物尼伐地平的制备方法

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
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
DE2248150A1 (de) *	1972-09-30	1974-04-04	Bayer Ag	Dihydropyridinpolyester, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel
DE2335466A1 (de) *	1973-07-12	1975-01-30	Bayer Ag	Alkoxyalkyl-1,4-dihydropyridine, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel
CH607848A5 (fr) *	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 AU AU31657/77A patent/AU518206B2/en not_active Expired
- 1977-12-16 JP JP52152290A patent/JPS5948828B2/ja not_active Expired
- 1977-12-16 FR FR7738126A patent/FR2374307A1/fr active Granted
- 1977-12-16 DK DK563377A patent/DK563377A/da not_active Application Discontinuation
- 1977-12-16 SE SE7714374A patent/SE7714374L/xx not_active Application Discontinuation
- 1977-12-16 BE BE183553A patent/BE861964A/fr not_active IP Right Cessation
- 1977-12-16 ES ES465137A patent/ES465137A1/es not_active Expired
- 1977-12-16 DE DE19772756226 patent/DE2756226A1/de not_active Ceased
- 1977-12-16 HU HU77FU358A patent/HU176454B/hu unknown
- 1977-12-16 AR AR270392A patent/AR221478A1/es active
- 1977-12-16 CH CH1553477A patent/CH633266A5/de not_active IP Right Cessation
- 1977-12-16 AT AT0901877A patent/AT367401B/de not_active IP Right Cessation
- 1977-12-19 ZA ZA00777532A patent/ZA777532B/xx unknown
- 1977-12-19 NL NL7714066A patent/NL7714066A/xx not_active Application Discontinuation
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/SE8204312D0/xx not_active Application Discontinuation

Also Published As

Publication number	Publication date
JPS5395977A (en)	1978-08-22
NL7714066A (nl)	1978-06-20
FR2374307B1 (fr)	1981-02-13
AU3165777A (en)	1979-06-21
SE8204312L (sv)	1982-07-13
ZA777532B (en)	1978-10-25
ES474233A1 (es)	1979-11-01
AR221887A1 (es)	1981-03-31
AR221478A1 (es)	1981-02-13
SE8204312D0 (sv)	1982-07-13
ES465137A1 (es)	1979-01-01
JPS5948828B2 (ja)	1984-11-29
DE2756226A1 (de)	1978-06-29
ATA901877A (de)	1981-11-15
BE861964A (fr)	1978-06-16
GB1591089A (en)	1981-06-10
HU176454B (en)	1981-03-28
ES474234A1 (es)	1979-04-01
AT367401B (de)	1982-07-12
DK172182A (da)	1982-04-16
DK563377A (da)	1978-06-18
AU518206B2 (en)	1981-09-17
SE7714374L (sv)	1978-06-18
FR2374307A1 (fr)	1978-07-13

Legal Events

Date	Code	Title	Description
1985-08-30	PL	Patent ceased
2024-10-31	PL	Patent ceased

Publication	Publication Date	Title
EP0071819B2 (fr)	1992-06-10	Dihydropyridines, douées d'une activité inotrope positive, leur application comme médicaments, et leurs procédés de préparation
CH633266A5 (en)	1982-11-30	Process for preparing 1,4-dihydropyridine compounds
EP0002208B1 (fr)	1981-03-11	Nitro dihydro-1,4 pyridines, médicaments les contenant et leur procédé de préparation
DE3529997C2 (de)	1996-01-18	Substituierte 4-Phenyl-1,4-dihydropyridincarbonsäureester
EP0088276B1 (fr)	1986-04-30	Composés, leurs procédés de préparation et leur application comme médicaments
DE3787346T2 (de)	1994-04-21	Dihydropyridin-Derivate, ihre Herstellung und ihre Verwendung.
CH629778A5 (de)	1982-05-14	Verfahren zur herstellung neuer 1,4-dihydropyridinderivate.
DE2935451A1 (de)	1981-03-19	Optisch aktive 1,4-dihydropyridine, verfahren zu ihrer herstellung und ihre verwendung als arneimittel
EP0114270B1 (fr)	1987-04-01	Dérivés acyliques de dianhydro-1,4:3,6 hexitols, procédé pour leur préparation et leur application comme médicaments
DE2940833C2 (fr)	1989-01-26
EP0088938A1 (fr)	1983-09-21	Application des dérivés de pyridine pour obtenir des medicaments datés d'une activité anti-hypoxémique et protectrice d'ischémie
EP0039863B1 (fr)	1983-12-28	Dihydro-1,4 pyridines comportant des substituants différents en positions 2 et 6, procédés pour leur préparation et leur utilisation dans des médicaments
DE3209274A1 (de)	1983-09-15	Pyridincarbonsaeureester, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel
EP0093945B1 (fr)	1988-11-23	Dérivés de 1,4-dihydropyridine
EP0627427A1 (fr)	1994-12-07	Dihydropyridines substituées par de 3-quinolyl, procédé pour leur production et leur utilisation dans des médicaments
DD235867A5 (de)	1986-05-21	Verfahren zur herstellung von 1,4-dihydropyridinen
EP0001108B1 (fr)	1981-04-29	1,4-Dihydropyridazines, procédé pour leur préparation et leur utilisation dans les produits pharmaceutiques
EP0106276B1 (fr)	1988-10-26	Dérivés de 1,4-dihydropyridine
DE60012355T2 (de)	2005-12-22	Phenyl- und pyridyl-tetrahydro-pyridine mit tnf inhibitorischer wirkung
DE3833892A1 (de)	1990-04-12	Basische 4-aryl-dhp-amide, verfahren zu ihrer herstellung und ihre verwendung in arzneimitteln
EP0225574B1 (fr)	1990-05-16	Dihydro-1,4 pyridines fluorées, procédé pour leur préparation et leur application comme médicaments
EP0173943A1 (fr)	1986-03-12	Pyridyléthyl-dihydropyridines, procédé pour leur préparation et leur utilisation dans des médicaments
EP0244595A2 (fr)	1987-11-11	Dérivés de dihydropyridine, leur procédé de préparation et leur application comme médicaments
AT360537B (de)	1981-01-12	Verfahren zur herstellung neuer 1,4-dihydro- pyridinderivate
EP0001439B1 (fr)	1981-01-28	Dérivés de la 1.4-dihydropyridazine 1-N-substitués, leur préparation et leur application pour des médicaments