SE459920B - Estrar av 4-(2-(2-karboxietenyl)fenyl)-dihydropyridindikarboxylsyror, foerfarande foer framstaellning av dessa och en farmaceutisk komposition - Google Patents

Estrar av 4-(2-(2-karboxietenyl)fenyl)-dihydropyridindikarboxylsyror, foerfarande foer framstaellning av dessa och en farmaceutisk komposition

Info

Publication number: SE459920B
Authority: SE; Sweden
Prior art keywords: formula; ester; group; dimethyl; alkyl group
Prior art date: 1984-08-22

Application number

SE8503888A

Other languages

English (en)

Swedish (sv)

Other versions

SE8503888D0 (sv

SE8503888L (sv

Inventor

C Semeraro

D Micheli

D Pieraccioli

G Gaviraghi

A D Borthwick

Original Assignee

Glaxo Spa

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.)

1984-08-22

Filing date

1985-08-20

Publication date

1989-08-21

1984-08-22 Priority claimed from IT22383/84A external-priority patent/IT1175620B/it

1985-07-05 Priority claimed from IT21460/85A external-priority patent/IT1187678B/it

1985-08-20 Application filed by Glaxo Spa filed Critical Glaxo Spa

1985-08-20 Publication of SE8503888D0 publication Critical patent/SE8503888D0/xx

1986-02-23 Publication of SE8503888L publication Critical patent/SE8503888L/xx

1989-08-21 Publication of SE459920B publication Critical patent/SE459920B/sv

Links

239000002253 acid Substances 0.000 title claims description 14
238000000034 method Methods 0.000 title claims description 11
239000008194 pharmaceutical composition Substances 0.000 title claims description 5
150000007513 acids Chemical class 0.000 title description 3
CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 96
-1 methoxyethyl Chemical group 0.000 claims description 41
239000000203 mixture Substances 0.000 claims description 31
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
125000000217 alkyl group Chemical group 0.000 claims description 16
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 10
BXSSKELATWFECN-UHFFFAOYSA-N 2,6-dimethyl-4-[2-[3-[(2-methylpropan-2-yl)oxy]-3-oxoprop-1-enyl]phenyl]-1,4-dihydropyridine-3,5-dicarboxylic acid Chemical compound OC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC=C1C=CC(=O)OC(C)(C)C BXSSKELATWFECN-UHFFFAOYSA-N 0.000 claims description 8
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 8
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 6
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
150000002148 esters Chemical class 0.000 claims description 6
239000001257 hydrogen Substances 0.000 claims description 6
229910052739 hydrogen Inorganic materials 0.000 claims description 6
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
125000000753 cycloalkyl group Chemical group 0.000 claims description 5
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 claims description 5
125000004430 oxygen atom Chemical group O* 0.000 claims description 5
238000002360 preparation method Methods 0.000 claims description 5
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
239000004480 active ingredient Substances 0.000 claims description 4
239000002775 capsule Substances 0.000 claims description 4
230000008569 process Effects 0.000 claims description 4
229930194542 Keto Natural products 0.000 claims description 3
125000003545 alkoxy group Chemical group 0.000 claims description 3
229910052794 bromium Inorganic materials 0.000 claims description 3
125000006225 propoxyethyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 3
125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 2
125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 2
230000001678 irradiating effect Effects 0.000 claims description 2
150000007530 organic bases Chemical class 0.000 claims description 2
150000002940 palladium Chemical class 0.000 claims description 2
125000004435 hydrogen atom Chemical class [H]* 0.000 claims 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
101100298295 Drosophila melanogaster flfl gene Proteins 0.000 claims 1
150000003863 ammonium salts Chemical class 0.000 claims 1
239000003085 diluting agent Substances 0.000 claims 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 1
GKQPCPXONLDCMU-UHFFFAOYSA-N lacidipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCC)C1C1=CC=CC=C1C=CC(=O)OC(C)(C)C GKQPCPXONLDCMU-UHFFFAOYSA-N 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 124
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 122
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 74
239000000243 solution Substances 0.000 description 41
239000000543 intermediate Substances 0.000 description 40
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 35
239000003208 petroleum Substances 0.000 description 28
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
239000002904 solvent Substances 0.000 description 24
239000007787 solid Substances 0.000 description 23
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
239000003921 oil Substances 0.000 description 16
150000001299 aldehydes Chemical class 0.000 description 15
238000006243 chemical reaction Methods 0.000 description 14
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
238000001704 evaporation Methods 0.000 description 11
230000008020 evaporation Effects 0.000 description 11
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
YPMPTULBFPFSEQ-PLNGDYQASA-N ethyl (z)-3-aminobut-2-enoate Chemical compound CCOC(=O)\C=C(\C)N YPMPTULBFPFSEQ-PLNGDYQASA-N 0.000 description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
238000002844 melting Methods 0.000 description 9
230000008018 melting Effects 0.000 description 9
239000000741 silica gel Substances 0.000 description 9
229910002027 silica gel Inorganic materials 0.000 description 9
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
239000003826 tablet Substances 0.000 description 8
238000010438 heat treatment Methods 0.000 description 7
239000000725 suspension Substances 0.000 description 7
BXSSKELATWFECN-ZHACJKMWSA-N 2,6-dimethyl-4-[2-[(e)-3-[(2-methylpropan-2-yl)oxy]-3-oxoprop-1-enyl]phenyl]-1,4-dihydropyridine-3,5-dicarboxylic acid Chemical compound OC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC=C1\C=C\C(=O)OC(C)(C)C BXSSKELATWFECN-ZHACJKMWSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
150000002576 ketones Chemical class 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
238000010992 reflux Methods 0.000 description 6
239000011734 sodium Substances 0.000 description 6
238000003756 stirring Methods 0.000 description 6
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
238000001914 filtration Methods 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
229910000027 potassium carbonate Inorganic materials 0.000 description 5
229940093956 potassium carbonate Drugs 0.000 description 5
235000011181 potassium carbonates Nutrition 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
239000007832 Na2SO4 Substances 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
238000004440 column chromatography Methods 0.000 description 4
239000000470 constituent Substances 0.000 description 4
IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
230000007306 turnover Effects 0.000 description 4
NDOPHXWIAZIXPR-UHFFFAOYSA-N 2-bromobenzaldehyde Chemical compound BrC1=CC=CC=C1C=O NDOPHXWIAZIXPR-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical compound COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
230000006835 compression Effects 0.000 description 3
238000007906 compression Methods 0.000 description 3
239000003814 drug Substances 0.000 description 3
229940079593 drug Drugs 0.000 description 3
230000000694 effects Effects 0.000 description 3
238000011049 filling Methods 0.000 description 3
150000002431 hydrogen Chemical class 0.000 description 3
230000007062 hydrolysis Effects 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
230000004048 modification Effects 0.000 description 3
238000012986 modification Methods 0.000 description 3
239000001267 polyvinylpyrrolidone Substances 0.000 description 3
229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
239000000047 product Substances 0.000 description 3
WQACUBIAIFEJIX-UHFFFAOYSA-N (2-methylcyclohexyl) methanesulfonate Chemical compound CC1CCCCC1OS(C)(=O)=O WQACUBIAIFEJIX-UHFFFAOYSA-N 0.000 description 2
ZIUMNQBNEUJSSL-AATRIKPKSA-N (e)-3-(2-formylphenyl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC=CC=C1C=O ZIUMNQBNEUJSSL-AATRIKPKSA-N 0.000 description 2
NEAHANDDKZCMSC-CCEZHUSRSA-N 2,6-dimethyl-4-[2-[(e)-3-octoxy-3-oxoprop-1-enyl]phenyl]-1,4-dihydropyridine-3,5-dicarboxylic acid Chemical compound CCCCCCCCOC(=O)\C=C\C1=CC=CC=C1C1C(C(O)=O)=C(C)NC(C)=C1C(O)=O NEAHANDDKZCMSC-CCEZHUSRSA-N 0.000 description 2
SBMQOMUSIIJTFV-MDZDMXLPSA-N 4-[2-[(e)-3-ethoxy-3-oxoprop-1-enyl]phenyl]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid Chemical compound CCOC(=O)\C=C\C1=CC=CC=C1C1C(C(O)=O)=C(C)NC(C)=C1C(O)=O SBMQOMUSIIJTFV-MDZDMXLPSA-N 0.000 description 2
WNGHWBLGGHLOET-UHFFFAOYSA-N 4-methyl-2-(2-methylpropyl)pentane-1-sulfonic acid Chemical compound CC(C)CC(CC(C)C)CS(O)(=O)=O WNGHWBLGGHLOET-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
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 2
239000012359 Methanesulfonyl chloride Substances 0.000 description 2
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
229920002565 Polyethylene Glycol 400 Polymers 0.000 description 2
ZWZUFQPXYVYAFO-UHFFFAOYSA-N Tert-butyl (triphenylphosphoranylidene)acetate Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OC(C)(C)C)C1=CC=CC=C1 ZWZUFQPXYVYAFO-UHFFFAOYSA-N 0.000 description 2
239000003377 acid catalyst Substances 0.000 description 2
229910052784 alkaline earth metal Inorganic materials 0.000 description 2
235000019270 ammonium chloride Nutrition 0.000 description 2
238000009835 boiling Methods 0.000 description 2
150000004768 bromobenzenes Chemical class 0.000 description 2
GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
229910001424 calcium ion Inorganic materials 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
230000008859 change Effects 0.000 description 2
239000012230 colorless oil Substances 0.000 description 2
239000010779 crude oil Substances 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentene Chemical compound C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 description 2
239000002270 dispersing agent Substances 0.000 description 2
XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
239000007903 gelatin capsule Substances 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
239000008101 lactose Substances 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
XKORCTIIRYKLLG-ARJAWSKDSA-N methyl (z)-3-aminobut-2-enoate Chemical compound COC(=O)\C=C(\C)N XKORCTIIRYKLLG-ARJAWSKDSA-N 0.000 description 2
UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 2
125000000896 monocarboxylic acid group Chemical group 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
239000012299 nitrogen atmosphere Substances 0.000 description 2
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
239000000843 powder Substances 0.000 description 2
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
238000010561 standard procedure Methods 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 2
230000002792 vascular Effects 0.000 description 2
239000008096 xylene Substances 0.000 description 2
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
APDGYQVYBWGBSD-UHFFFAOYSA-N 1-bromo-2-(diethoxymethyl)benzene Chemical compound CCOC(OCC)C1=CC=CC=C1Br APDGYQVYBWGBSD-UHFFFAOYSA-N 0.000 description 1
HLVFKOKELQSXIQ-UHFFFAOYSA-N 1-bromo-2-methylpropane Chemical compound CC(C)CBr HLVFKOKELQSXIQ-UHFFFAOYSA-N 0.000 description 1
VMKOFRJSULQZRM-UHFFFAOYSA-N 1-bromooctane Chemical compound CCCCCCCCBr VMKOFRJSULQZRM-UHFFFAOYSA-N 0.000 description 1
BFDNZQUBFCYTIC-UHFFFAOYSA-N 1-bromotridecane Chemical compound CCCCCCCCCCCCCBr BFDNZQUBFCYTIC-UHFFFAOYSA-N 0.000 description 1
KAMMLXOLERSLOG-OUKQBFOZSA-N 2,6-diethyl-4-[2-[(e)-3-[(2-methylpropan-2-yl)oxy]-3-oxoprop-1-enyl]phenyl]-1,4-dihydropyridine-3,5-dicarboxylic acid Chemical compound OC(=O)C1=C(CC)NC(CC)=C(C(O)=O)C1C1=CC=CC=C1\C=C\C(=O)OC(C)(C)C KAMMLXOLERSLOG-OUKQBFOZSA-N 0.000 description 1
BXSSKELATWFECN-KHPPLWFESA-N 2,6-dimethyl-4-[2-[(Z)-3-[(2-methylpropan-2-yl)oxy]-3-oxoprop-1-enyl]phenyl]-1,4-dihydropyridine-3,5-dicarboxylic acid Chemical compound OC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC=C1\C=C/C(=O)OC(C)(C)C BXSSKELATWFECN-KHPPLWFESA-N 0.000 description 1
AEUWJPSQEHHSBZ-OUKQBFOZSA-N 2,6-dimethyl-4-[2-[(e)-3-(2-methylcyclohexyl)oxy-3-oxoprop-1-enyl]phenyl]-1,4-dihydropyridine-3,5-dicarboxylic acid Chemical compound CC1CCCCC1OC(=O)\C=C\C1=CC=CC=C1C1C(C(O)=O)=C(C)NC(C)=C1C(O)=O AEUWJPSQEHHSBZ-OUKQBFOZSA-N 0.000 description 1
MVNBODWKCWSYAK-MDZDMXLPSA-N 2,6-dimethyl-4-[2-[(e)-3-(2-methylpropoxy)-3-oxoprop-1-enyl]phenyl]-1,4-dihydropyridine-3,5-dicarboxylic acid Chemical compound CC(C)COC(=O)\C=C\C1=CC=CC=C1C1C(C(O)=O)=C(C)NC(C)=C1C(O)=O MVNBODWKCWSYAK-MDZDMXLPSA-N 0.000 description 1
TVFBFTRGAKLKSJ-MDZDMXLPSA-N 2,6-dimethyl-4-[2-[(e)-3-oxo-3-propan-2-yloxyprop-1-enyl]phenyl]-1,4-dihydropyridine-3,5-dicarboxylic acid Chemical compound CC(C)OC(=O)\C=C\C1=CC=CC=C1C1C(C(O)=O)=C(C)NC(C)=C1C(O)=O TVFBFTRGAKLKSJ-MDZDMXLPSA-N 0.000 description 1
HHYOOLILMDESPS-UHFFFAOYSA-N 2-(diethoxymethyl)benzaldehyde Chemical compound CCOC(OCC)C1=CC=CC=C1C=O HHYOOLILMDESPS-UHFFFAOYSA-N 0.000 description 1
ZYXNLVMBIHVDRH-UHFFFAOYSA-N 2-Methylpropyl 3-oxobutanoate Chemical compound CC(C)COC(=O)CC(C)=O ZYXNLVMBIHVDRH-UHFFFAOYSA-N 0.000 description 1
QEBHNNUORVRFOM-UHFFFAOYSA-N 2-[2-[3-[(2-methylpropan-2-yl)oxy]-3-oxoprop-1-enyl]phenyl]-3-oxopent-4-enoic acid Chemical compound CC(C)(C)OC(=O)C=CC1=CC=CC=C1C(C(O)=O)C(=O)C=C QEBHNNUORVRFOM-UHFFFAOYSA-N 0.000 description 1
125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
WWKKTHALZAYYAI-UHFFFAOYSA-N 2-iodobenzaldehyde Chemical compound IC1=CC=CC=C1C=O WWKKTHALZAYYAI-UHFFFAOYSA-N 0.000 description 1
125000006304 2-iodophenyl group Chemical group [H]C1=C([H])C(I)=C(*)C([H])=C1[H] 0.000 description 1
PLHCSZRZWOWUBW-UHFFFAOYSA-N 2-methoxyethyl 3-oxobutanoate Chemical compound COCCOC(=O)CC(C)=O PLHCSZRZWOWUBW-UHFFFAOYSA-N 0.000 description 1
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
PBJZBRWKTBIWOK-FPLPWBNLSA-N 2-propoxyethyl (z)-3-aminobut-2-enoate Chemical compound CCCOCCOC(=O)\C=C(\C)N PBJZBRWKTBIWOK-FPLPWBNLSA-N 0.000 description 1
BBBJXPCSKOPGLI-UHFFFAOYSA-N 2-propoxyethyl 3-oxobutanoate Chemical compound CCCOCCOC(=O)CC(C)=O BBBJXPCSKOPGLI-UHFFFAOYSA-N 0.000 description 1
XWOJSJJIRMYPJS-VAWYXSNFSA-N 4-[2-[(e)-3-(2,6-dimethylheptan-4-yloxy)-3-oxoprop-1-enyl]phenyl]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid Chemical compound CC(C)CC(CC(C)C)OC(=O)\C=C\C1=CC=CC=C1C1C(C(O)=O)=C(C)NC(C)=C1C(O)=O XWOJSJJIRMYPJS-VAWYXSNFSA-N 0.000 description 1
JBRFSYPUGPNICM-BUHFOSPRSA-N 4-[2-[(e)-3-cycloheptyloxy-3-oxoprop-1-enyl]phenyl]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid Chemical compound OC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC=C1\C=C\C(=O)OC1CCCCCC1 JBRFSYPUGPNICM-BUHFOSPRSA-N 0.000 description 1
ZZYNLIRJOPEKQD-OUKQBFOZSA-N 4-[2-[(e)-3-cyclohexyloxy-3-oxoprop-1-enyl]phenyl]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid Chemical compound OC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC=C1\C=C\C(=O)OC1CCCCC1 ZZYNLIRJOPEKQD-OUKQBFOZSA-N 0.000 description 1
JNPGETGJEXZRIJ-VAWYXSNFSA-N 4-[2-[(e)-3-cyclopentyloxy-3-oxoprop-1-enyl]phenyl]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid Chemical compound OC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC=C1\C=C\C(=O)OC1CCCC1 JNPGETGJEXZRIJ-VAWYXSNFSA-N 0.000 description 1
DPRONSIVANUTIH-VAWYXSNFSA-N 5-methoxycarbonyl-2,6-dimethyl-4-[2-[(e)-3-[(2-methylpropan-2-yl)oxy]-3-oxoprop-1-enyl]phenyl]-1,4-dihydropyridine-3-carboxylic acid Chemical compound COC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC=C1\C=C\C(=O)OC(C)(C)C DPRONSIVANUTIH-VAWYXSNFSA-N 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 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
206010002383 Angina Pectoris Diseases 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
206010007559 Cardiac failure congestive Diseases 0.000 description 1
208000024172 Cardiovascular disease Diseases 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
HXQPUEQDBSPXTE-UHFFFAOYSA-N Diisobutylcarbinol Chemical compound CC(C)CC(O)CC(C)C HXQPUEQDBSPXTE-UHFFFAOYSA-N 0.000 description 1
241000792859 Enema Species 0.000 description 1
239000001856 Ethyl cellulose Substances 0.000 description 1
ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
206010019280 Heart failures Diseases 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 1
239000002202 Polyethylene glycol Substances 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
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
239000003513 alkali Substances 0.000 description 1
150000004703 alkoxides Chemical class 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
229940043376 ammonium acetate Drugs 0.000 description 1
235000019257 ammonium acetate Nutrition 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
230000003276 anti-hypertensive effect Effects 0.000 description 1
239000000010 aprotic solvent Substances 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000008135 aqueous vehicle Substances 0.000 description 1
239000002585 base Substances 0.000 description 1
LOXORFRCPXUORP-UHFFFAOYSA-N bromo-Cycloheptane Chemical compound BrC1CCCCCC1 LOXORFRCPXUORP-UHFFFAOYSA-N 0.000 description 1
AQNQQHJNRPDOQV-UHFFFAOYSA-N bromocyclohexane Chemical compound BrC1CCCCC1 AQNQQHJNRPDOQV-UHFFFAOYSA-N 0.000 description 1
BRTFVKHPEHKBQF-UHFFFAOYSA-N bromocyclopentane Chemical compound BrC1CCCC1 BRTFVKHPEHKBQF-UHFFFAOYSA-N 0.000 description 1
CQEYYJKEWSMYFG-UHFFFAOYSA-N butyl acrylate Chemical group CCCCOC(=O)C=C CQEYYJKEWSMYFG-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
230000002490 cerebral effect Effects 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
229940114081 cinnamate Drugs 0.000 description 1
238000013329 compounding Methods 0.000 description 1
239000006071 cream Substances 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
239000007920 enema Substances 0.000 description 1
229940095399 enema Drugs 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
235000019325 ethyl cellulose Nutrition 0.000 description 1
229920001249 ethyl cellulose Polymers 0.000 description 1
238000005194 fractionation Methods 0.000 description 1
239000008187 granular material Substances 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
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
230000004941 influx Effects 0.000 description 1
238000001802 infusion Methods 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
238000006317 isomerization reaction Methods 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
239000000463 material Substances 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
229940102396 methyl bromide Drugs 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
238000002156 mixing Methods 0.000 description 1
208000031225 myocardial ischemia Diseases 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
GRJPLADOIKKOGS-UHFFFAOYSA-N octyl methanesulfonate Chemical compound CCCCCCCCOS(C)(=O)=O GRJPLADOIKKOGS-UHFFFAOYSA-N 0.000 description 1
239000002674 ointment Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
239000012071 phase Substances 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
ZWLUXSQADUDCSB-UHFFFAOYSA-N phthalaldehyde Chemical compound O=CC1=CC=CC=C1C=O ZWLUXSQADUDCSB-UHFFFAOYSA-N 0.000 description 1
239000003880 polar aprotic solvent Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
YCKAGGHNUHZKCL-XQRVVYSFSA-N propan-2-yl (z)-3-aminobut-2-enoate Chemical compound CC(C)OC(=O)\C=C(\C)N YCKAGGHNUHZKCL-XQRVVYSFSA-N 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
238000011699 spontaneously hypertensive rat Methods 0.000 description 1
230000006641 stabilisation Effects 0.000 description 1
238000011105 stabilization Methods 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
238000013517 stratification Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 1
RKSOPLXZQNSWAS-UHFFFAOYSA-N tert-butyl bromide Chemical compound CC(C)(C)Br RKSOPLXZQNSWAS-UHFFFAOYSA-N 0.000 description 1
ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
238000012360 testing method Methods 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
125000002889 tridecyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
IIHPVYJPDKJYOU-UHFFFAOYSA-N triphenylcarbethoxymethylenephosphorane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OCC)C1=CC=CC=C1 IIHPVYJPDKJYOU-UHFFFAOYSA-N 0.000 description 1
FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
239000000052 vinegar Substances 0.000 description 1
235000021419 vinegar Nutrition 0.000 description 1
238000005406 washing Methods 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
- A61P3/00—Drugs for disorders of the metabolism
- 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
- 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
- C03—GLASS; MINERAL OR SLAG WOOL
- C03B—MANUFACTURE, SHAPING, OR SUPPLEMENTARY PROCESSES
- C03B2205/00—Fibre drawing or extruding details
- C03B2205/44—Monotoring or regulating the preform feed rate

Landscapes

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

SE8503888A 1984-08-22 1985-08-20 Estrar av 4-(2-(2-karboxietenyl)fenyl)-dihydropyridindikarboxylsyror, foerfarande foer framstaellning av dessa och en farmaceutisk komposition SE459920B (sv)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
IT22383/84A IT1175620B (it)	1984-08-22	1984-08-22	Derivati piridinici
IT21460/85A IT1187678B (it)	1985-07-05	1985-07-05	Procedimento di preparazione di derivati eterociclici

Publications (3)

Publication Number	Publication Date
SE8503888D0 SE8503888D0 (sv)	1985-08-20
SE8503888L SE8503888L (sv)	1986-02-23
SE459920B true SE459920B (sv)	1989-08-21

Family

ID=26327905

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SE8503888A SE459920B (sv)	1984-08-22	1985-08-20	Estrar av 4-(2-(2-karboxietenyl)fenyl)-dihydropyridindikarboxylsyror, foerfarande foer framstaellning av dessa och en farmaceutisk komposition

Country Status (33)

Country	Link
US (2)	US4801599A (bg)
JP (2)	JPS6193162A (bg)
KR (1)	KR920004482B1 (bg)
AT (1)	AT394042B (bg)
AU (1)	AU578724B2 (bg)
BE (1)	BE903103A (bg)
BG (1)	BG60409B2 (bg)
CA (1)	CA1268180A (bg)
CH (1)	CH666684A5 (bg)
CS (1)	CS403091A3 (bg)
CY (1)	CY1494A (bg)
DE (1)	DE3529997C2 (bg)
DK (1)	DK165949C (bg)
ES (5)	ES8703839A1 (bg)
FI (1)	FI81568C (bg)
FR (1)	FR2569402B1 (bg)
GB (1)	GB2164336B (bg)
GR (1)	GR852016B (bg)
HK (1)	HK52990A (bg)
HU (1)	HU196754B (bg)
IE (1)	IE58486B1 (bg)
LU (2)	LU88267I2 (bg)
MX (1)	MX159974A (bg)
NL (2)	NL193065C (bg)
NO (2)	NO167142C (bg)
NZ (1)	NZ212895A (bg)
PH (1)	PH22014A (bg)
PT (1)	PT81000B (bg)
SA (1)	SA91120277B1 (bg)
SE (1)	SE459920B (bg)
SG (1)	SG40889G (bg)
SK (1)	SK278327B6 (bg)
ZW (1)	ZW13185A1 (bg)

Families Citing this family (39)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
NZ212895A (en) *	1984-08-22	1988-07-28	Glaxo Spa	1,4-dihydropyridine derivatives and pharmaceutical compositions
EP0226271B1 (en) *	1985-08-21	1990-11-22	GLAXO S.p.A.	1,4-dihydropyridine compounds and their preparation and pharmaceutical formulation
JPH0696552B2 (ja) *	1985-08-21	1994-11-30	グラクソ・ソシエタ・ペル・アツイオ−ニ	複素環式化合物
IT1204461B (it) *	1986-02-20	1989-03-01	Glaxo Spa	Derivati eterociclici
IT1204462B (it) *	1986-02-20	1989-03-01	Glaxo Spa	Derivati eterociclici
IT1204460B (it) *	1986-02-20	1989-03-01	Glaxo Spa	Derivati eterociclici
IT1233370B (it) *	1988-11-21	1992-03-27	Glaxo Spa	Procedimento di preparazione di derivati diidropipiridinici utili nel trattamento di disturbi cardiovascolari
DE69030982T2 (de)	1989-04-27	1997-11-13	Canon Kk	Optisches Aufzeichnungsmedium und Verfahren zu seiner Herstellung
US5196529A (en) *	1990-10-09	1993-03-23	Merck & Co., Inc.	2-phenanthrenyl carbapenem intermediates
US5177202A (en) *	1990-10-09	1993-01-05	Merck & Co., Inc.	2-phenanthrenyl-carbapenems
US5132422A (en) *	1990-10-09	1992-07-21	Merck & Co., Inc.	2-naphthyl-carbapenem intermediates
US5132421A (en) *	1990-10-09	1992-07-21	Merck & Co., Inc.	2-naphthyl-carbapenem intermediates
US5356889A (en) *	1990-08-01	1994-10-18	Merck & Co., Inc.	2-(9-fluorenonyl)-carbapenem intermediates
US5144028A (en) *	1990-10-09	1992-09-01	Merck & Co., Inc.	2-(9-fluorenonyl)-carbapenem intermediates
US5208329A (en) *	1990-10-09	1993-05-04	Merck & Co., Inc.	2-biphenyl carbapenem intermediates
IT1244728B (it) *	1991-02-13	1994-08-08	Glaxo Spa	Impiego medicamentoso di derivati diidropiridinici
TW483763B (en) *	1994-09-02	2002-04-21	Astra Ab	Pharmaceutical composition comprising of ramipril and dihydropyridine compound
AU1042199A (en) *	1998-11-06	2000-05-29	Boehringer Ingelheim International Gmbh	Antihypertensive medicaments containing lacidipine and telmisartan
GEP20074134B (en)	2002-08-19	2007-06-25	Pfizer Prod Inc	Combination therapy for hyperproliferative diseases
AP2501A (en) *	2003-05-30	2012-10-22	Ranbaxy Lab Ltd	Substituted pyrrole derivatives
US20050037063A1 (en) *	2003-07-21	2005-02-17	Bolton Anthony E.	Combined therapies
US20060147520A1 (en) *	2004-07-26	2006-07-06	Curtis Ruegg	Treatment of pulmonary hypertension by inhaled iloprost with a microparticle formulation
EP1868577A4 (en)	2005-04-15	2009-12-09	Reddys Lab Inc Dr	Lacidipine PARTICLE
US20070043088A1 (en) *	2005-08-16	2007-02-22	Eswaraiah Sajja	Process for preparing lacidipine
US7741317B2 (en)	2005-10-21	2010-06-22	Bristol-Myers Squibb Company	LXR modulators
EP2351569B1 (en)	2005-10-26	2012-08-22	Asahi Kasei Pharma Corporation	Fasudil in combination therapies for the treatment of pulmonary arterial hypertension
JP2009513660A (ja)	2005-10-26	2009-04-02	旭化成ファーマ株式会社	肺動脈性高血圧の治療用併用療法におけるファスジル
KR101329112B1 (ko) *	2005-11-08	2013-11-14	랜박시 래보러터리스 리미티드	(3ｒ,5ｒ)-7-〔2-(4-플루오로페닐)-5-이소프로필-3-페닐-4-〔(4-히드록시 메틸 페닐 아미노)카르보닐〕-피롤-1-일〕-3,5-디히드록시 헵탄산 헤미 칼슘염의 제조 방법
US7888376B2 (en)	2005-11-23	2011-02-15	Bristol-Myers Squibb Company	Heterocyclic CETP inhibitors
US7919506B2 (en)	2006-03-10	2011-04-05	Pfizer Inc.	Dibenzyl amine compounds and derivatives
CL2007000667A1 (es) *	2006-03-14	2008-03-14	Ranbaxi Lab Ltd	Composicion farmaceutica que comprende al acido 7-[2-(4-fluorofenil)-5-isopropil-3-fenil-4-[(4-hidroximetilfenilamino)carbonil]pirrol-1-il]-3,5-dihidroxi-heptanoico o una sal y al menos un agente estabilizante; procedimiento de preparacion, util en e
EP2049102A4 (en) *	2006-07-14	2010-12-22	Ranbaxy Lab Ltd	POLYMORPHIC FORMS OF AN HMG COA REDUCTASE HEATHER AND USE
US20080089947A1 (en) *	2006-08-18	2008-04-17	Knox Clayton D	Calcium Influx Inhibitors in the Treatment of Ischemia
ATE547394T1 (de)	2006-12-01	2012-03-15	Bristol Myers Squibb Co	N-((3-benzyl)-2,2-(bis-phenyl)-propan-1- aminderivate als cetp-hemmer für die behandlung von atherosklerose und herz-kreislauf- erkrankungen
WO2012037665A1 (en)	2010-09-24	2012-03-29	Oral Delivery Technology Ltd.	Nitric oxide releasing amino acid ester for treatment of pulmonary hypertension and other respiratory conditions
PL2705839T3 (pl)	2012-09-10	2018-07-31	Rivopharm Sa	Farmaceutyczna kompozycja zawierająca lacydypinę i proces przygotowania
KR101695582B1 (ko)	2013-04-17	2017-01-13	화이자 인코포레이티드	심혈관 질환을 치료하기 위한 n-피페리딘-3-일벤즈아미드 유도체
WO2016055901A1 (en)	2014-10-08	2016-04-14	Pfizer Inc.	Substituted amide compounds
MX2021008533A (es)	2019-01-18	2021-08-19	Astrazeneca Ab	Inhibidores de la pcsk9 y metodos de uso de los mismos.

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3455945A (en) *	1967-06-07	1969-07-15	Smithkline Corp	4-(carboxy (and carbo-lower alkoxy)phenyl)-1,4-dihydropyridines
DE2228363A1 (de) *	1972-06-10	1974-01-03	Bayer Ag	1,4-dihydropyridine, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel
GB1409865A (en) *	1973-02-13	1975-10-15	Science Union & Cie	Dihydropyridines derivatives their preparation and pharmaceu tical compositions containing them
US4307103A (en) *	1978-09-08	1981-12-22	Fujisawa Pharmaceutical Co., Ltd.	Dihydropyridine derivative, processes for preparation thereof and pharmaceutical composition comprising the same
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
NZ201395A (en) *	1981-07-30	1987-02-20	Bayer Ag	Pharmaceutical compositions containing 1,4-dihydropyridines and certain of these dihydropyridines
DE3207982A1 (de) *	1982-03-05	1983-09-08	Bayer Ag, 5090 Leverkusen	Neue 1,4-dihydropyridine, verfahren zu ihrer herstellung und ihrer verwendung in arzneimitteln
NZ212895A (en) *	1984-08-22	1988-07-28	Glaxo Spa	1,4-dihydropyridine derivatives and pharmaceutical compositions

1985
- 1985-07-29 NZ NZ212895A patent/NZ212895A/xx unknown
- 1985-08-20 GR GR852016A patent/GR852016B/el unknown
- 1985-08-20 NL NL8502296A patent/NL193065C/nl not_active IP Right Cessation
- 1985-08-20 DK DK378085A patent/DK165949C/da not_active IP Right Cessation
- 1985-08-20 SE SE8503888A patent/SE459920B/sv not_active IP Right Cessation
- 1985-08-20 US US06/767,593 patent/US4801599A/en not_active Expired - Lifetime
- 1985-08-20 ZW ZW131/85A patent/ZW13185A1/xx unknown
- 1985-08-21 NO NO853293A patent/NO167142C/no not_active IP Right Cessation
- 1985-08-21 FI FI853206A patent/FI81568C/fi not_active IP Right Cessation
- 1985-08-21 IE IE205485A patent/IE58486B1/en not_active IP Right Cessation
- 1985-08-21 CH CH3593/85A patent/CH666684A5/de not_active IP Right Cessation
- 1985-08-21 LU LU88267C patent/LU88267I2/xx unknown
- 1985-08-21 MX MX206376A patent/MX159974A/es unknown
- 1985-08-21 LU LU86047A patent/LU86047A1/fr active Protection Beyond IP Right Term
- 1985-08-21 GB GB08520924A patent/GB2164336B/en not_active Expired
- 1985-08-21 CY CY1494A patent/CY1494A/en unknown
- 1985-08-21 JP JP60181934A patent/JPS6193162A/ja active Granted
- 1985-08-21 ES ES546324A patent/ES8703839A1/es not_active Expired
- 1985-08-22 PT PT81000A patent/PT81000B/pt unknown
- 1985-08-22 FR FR8512631A patent/FR2569402B1/fr not_active Expired
- 1985-08-22 DE DE3529997A patent/DE3529997C2/de not_active Expired - Lifetime
- 1985-08-22 HU HU853202A patent/HU196754B/hu unknown
- 1985-08-22 BE BE0/215493A patent/BE903103A/fr not_active IP Right Cessation
- 1985-08-22 AT AT0245485A patent/AT394042B/de not_active IP Right Cessation
- 1985-08-22 KR KR1019850006044A patent/KR920004482B1/ko not_active Expired
- 1985-08-22 PH PH32680A patent/PH22014A/en unknown
- 1985-08-22 AU AU46576/85A patent/AU578724B2/en not_active Expired
- 1985-08-22 CA CA000489261A patent/CA1268180A/en not_active Expired - Lifetime
1986
- 1986-02-14 ES ES552050A patent/ES8707930A1/es not_active Expired
- 1986-02-14 ES ES552048A patent/ES8707931A1/es not_active Expired
- 1986-02-14 ES ES552051A patent/ES8707932A1/es not_active Expired
- 1986-02-14 ES ES552049A patent/ES8802497A1/es not_active Expired
1988
- 1988-07-27 JP JP63185661A patent/JPH0686430B2/ja not_active Expired - Lifetime
1989
- 1989-01-23 US US07/300,022 patent/US5011848A/en not_active Expired - Lifetime
- 1989-07-06 SG SG40889A patent/SG40889G/en unknown
1990
- 1990-07-12 HK HK529/90A patent/HK52990A/xx not_active IP Right Cessation
1991
- 1991-12-16 SA SA91120277A patent/SA91120277B1/ar unknown
- 1991-12-23 CS CS914030A patent/CS403091A3/cs unknown
- 1991-12-23 SK SK4030-91A patent/SK278327B6/sk unknown
1993
- 1993-08-20 BG BG098061A patent/BG60409B2/bg unknown
1998
- 1998-11-27 NL NL980037C patent/NL980037I2/nl unknown
1999
- 1999-04-23 NO NO1999007C patent/NO1999007I1/no unknown

Also Published As

Publication number	Publication date
DK165949B (da)	1993-02-15
NL980037I1 (nl)	1999-02-01
PH22014A (en)	1988-05-02
SE8503888D0 (sv)	1985-08-20
CA1268180A (en)	1990-04-24
DE3529997A1 (de)	1986-03-06
BG60409B2 (bg)	1995-02-28
SA91120277B1 (ar)	2006-05-15
NL193065B (nl)	1998-05-06
JPS6193162A (ja)	1986-05-12
AU4657685A (en)	1986-02-27
ES8707931A1 (es)	1987-09-01
HUT40625A (en)	1987-01-28
NO1999007I1 (no)	1999-04-23
CS403091A3 (en)	1992-06-17
GB2164336A (en)	1986-03-19
SG40889G (en)	1989-12-22
IE852054L (en)	1986-02-22
NZ212895A (en)	1988-07-28
FI81568B (fi)	1990-07-31
SE8503888L (sv)	1986-02-23
IE58486B1 (en)	1993-09-22
DK378085D0 (da)	1985-08-20
HK52990A (en)	1990-07-20
JPH0686430B2 (ja)	1994-11-02
DK378085A (da)	1986-02-23
DK165949C (da)	1993-07-05
FI853206A0 (fi)	1985-08-21
FR2569402B1 (fr)	1989-09-22
PT81000B (pt)	1988-03-03
FI853206L (fi)	1986-02-23
JPH0550506B2 (bg)	1993-07-29
AU578724B2 (en)	1988-11-03
NL980037I2 (nl)	1999-03-01
LU86047A1 (fr)	1986-02-28
ZW13185A1 (en)	1986-03-19
NO167142C (no)	1991-10-09
US5011848A (en)	1991-04-30
ES552049A0 (es)	1988-07-01
GB8520924D0 (en)	1985-09-25
ATA245485A (de)	1991-07-15
ES552048A0 (es)	1987-09-01
MX159974A (es)	1989-10-17
FI81568C (fi)	1990-11-12
ES552051A0 (es)	1987-09-01
LU88267I2 (bg)	1994-02-03
JPS6479152A (en)	1989-03-24
GR852016B (bg)	1985-12-19
SK278327B6 (en)	1996-11-06
US4801599A (en)	1989-01-31
ES8707930A1 (es)	1987-09-01
DE3529997C2 (de)	1996-01-18
CH666684A5 (de)	1988-08-15
NL8502296A (nl)	1986-03-17
ES546324A0 (es)	1987-03-01
FR2569402A1 (fr)	1986-02-28
AT394042B (de)	1992-01-27
KR920004482B1 (ko)	1992-06-05
CY1494A (en)	1990-02-16
NO167142B (no)	1991-07-01
PT81000A (en)	1985-09-01
KR870002073A (ko)	1987-03-28
NO853293L (no)	1986-02-24
HU196754B (en)	1989-01-30
BE903103A (fr)	1986-02-24
GB2164336B (en)	1988-06-08
ES8703839A1 (es)	1987-03-01
ES552050A0 (es)	1987-09-01
ES8707932A1 (es)	1987-09-01
ES8802497A1 (es)	1988-07-01
NL193065C (nl)	1998-09-08

Publication	Publication Date	Title
SE459920B (sv)	1989-08-21	Estrar av 4-(2-(2-karboxietenyl)fenyl)-dihydropyridindikarboxylsyror, foerfarande foer framstaellning av dessa och en farmaceutisk komposition
FI93007B (fi)	1994-10-31	Menetelmä terapeuttisesti käyttökelpoisten substituoitujen pyridiinien valmistamiseksi sekä menetelmässä käyttökelpoiset välituotteet
JPH06234741A (ja)	1994-08-23	置換４−フエニルピリドン及び４−フエニル−２−アルコキシピリジン
CH633266A5 (en)	1982-11-30	Process for preparing 1,4-dihydropyridine compounds
HU208691B (en)	1993-12-28	Method for producing disubstituted pyridine derivatives and medical preparatives containing them
US4946851A (en)	1990-08-07	1.4-dihydropyridines
US4963571A (en)	1990-10-16	Pyridinedicarboxylic acid derivatives and pharmaceutical compositions
EP0226271B1 (en)	1990-11-22	1,4-dihydropyridine compounds and their preparation and pharmaceutical formulation
US5162345A (en)	1992-11-10	Heterocyclic compounds and their preparation and pharmaceutical formulation
KR950011410B1 (ko)	1995-10-04	헤테로사이클릭 화합물의 제조방법
AU707289B2 (en)	1999-07-08	Method of preparing phosphodiesterase IV inhibitors
JPH09221449A (ja)	1997-08-26	α位に不斉炭素を有するカルボン酸の光学分割方法
NO174419B (no)	1994-01-24	Analogifremgangsmaate for fremstilling av terapeutisk aktive heterocykliske forbindelser
EP0242950A2 (en)	1987-10-28	dihydropyridines, process for their preparation and their use as therapeutics

Legal Events

Date	Code	Title	Description
1995-01-31	NAL	Patent in force	Ref document number: 8503888-3 Format of ref document f/p: F
1997-11-03	SPCF	Application for supplementary protection certificate filed	Free format text: 9790041, 970613
1997-12-08	SPCG	Supplementary protection certificate granted	Free format text: 9790041, 970613, EXPIRES: 20051106
2005-10-04	NUG	Patent has lapsed