FI58772C - Foerfarande foer framstaellning av hjaernblodaodror utvidgande 2,6-dimetyl-4-substituerad-fenyl-1,4-dihydropyridin-3-karboxylsyra-aminoalkylestrar - Google Patents
Foerfarande foer framstaellning av hjaernblodaodror utvidgande 2,6-dimetyl-4-substituerad-fenyl-1,4-dihydropyridin-3-karboxylsyra-aminoalkylestrar Download PDFInfo
- Publication number
- FI58772C FI58772C FI446/74A FI44674A FI58772C FI 58772 C FI58772 C FI 58772C FI 446/74 A FI446/74 A FI 446/74A FI 44674 A FI44674 A FI 44674A FI 58772 C FI58772 C FI 58772C
- Authority
- FI
- Finland
- Prior art keywords
- formula
- group
- defined above
- ester
- compound
- Prior art date
Links
- 238000000034 method Methods 0.000 title description 18
- 150000001875 compounds Chemical class 0.000 claims description 51
- WDJHALXBUFZDSR-UHFFFAOYSA-N Acetoacetic acid Natural products CC(=O)CC(O)=O WDJHALXBUFZDSR-UHFFFAOYSA-N 0.000 claims description 29
- -1 2,6-dimethyl-4-substituted-phenyl-1,4-dihydropyridine-3-carboxylic acid aminoalkyl ester Chemical class 0.000 claims description 28
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 150000001412 amines Chemical class 0.000 claims description 7
- UKVYVZLTGQVOPX-IHWYPQMZSA-N (z)-3-aminobut-2-enoic acid Chemical compound C\C(N)=C\C(O)=O UKVYVZLTGQVOPX-IHWYPQMZSA-N 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 150000002081 enamines Chemical class 0.000 claims description 6
- 150000003935 benzaldehydes Chemical class 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims 2
- LWWLBPBXAWGRBQ-UHFFFAOYSA-N 1-phenyl-4h-pyridine-3-carboxylic acid Chemical compound C1=CCC(C(=O)O)=CN1C1=CC=CC=C1 LWWLBPBXAWGRBQ-UHFFFAOYSA-N 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Natural products C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 150000002576 ketones Chemical class 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 229940124549 vasodilator Drugs 0.000 claims 1
- 239000003071 vasodilator agent Substances 0.000 claims 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 120
- 239000000243 solution Substances 0.000 description 86
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 80
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 70
- 239000000047 product Substances 0.000 description 67
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 49
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 49
- 239000000203 mixture Substances 0.000 description 42
- 239000011541 reaction mixture Substances 0.000 description 36
- 238000000921 elemental analysis Methods 0.000 description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- 239000013078 crystal Substances 0.000 description 22
- 238000002844 melting Methods 0.000 description 22
- 230000008018 melting Effects 0.000 description 22
- ZETIVVHRRQLWFW-UHFFFAOYSA-N 3-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC(C=O)=C1 ZETIVVHRRQLWFW-UHFFFAOYSA-N 0.000 description 20
- 239000002904 solvent Substances 0.000 description 20
- 125000004494 ethyl ester group Chemical group 0.000 description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- WOWBFOBYOAGEEA-UHFFFAOYSA-N diafenthiuron Chemical compound CC(C)C1=C(NC(=S)NC(C)(C)C)C(C(C)C)=CC(OC=2C=CC=CC=2)=C1 WOWBFOBYOAGEEA-UHFFFAOYSA-N 0.000 description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 16
- TZDPJNSHSWMCPN-UHFFFAOYSA-N 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid Chemical compound OC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC([N+]([O-])=O)=C1 TZDPJNSHSWMCPN-UHFFFAOYSA-N 0.000 description 15
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
- 239000010410 layer Substances 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 10
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 10
- 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 10
- 229960001597 nifedipine Drugs 0.000 description 10
- 238000004809 thin layer chromatography Methods 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 229940126062 Compound A Drugs 0.000 description 8
- 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 8
- 229960001789 papaverine Drugs 0.000 description 8
- 229920006395 saturated elastomer Polymers 0.000 description 8
- 230000002490 cerebral effect Effects 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 238000002329 infrared spectrum Methods 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 229930008281 A03AD01 - Papaverine Natural products 0.000 description 6
- 241000282472 Canis lupus familiaris Species 0.000 description 6
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 210000001105 femoral artery Anatomy 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 230000002048 spasmolytic effect Effects 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 210000002385 vertebral artery Anatomy 0.000 description 6
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 230000000304 vasodilatating effect Effects 0.000 description 5
- COLPLFZHPXIFCQ-UHFFFAOYSA-N 1,4-dihydropyridine-3,5-dicarboxylic acid Chemical class OC(=O)C1=CNC=C(C(O)=O)C1 COLPLFZHPXIFCQ-UHFFFAOYSA-N 0.000 description 4
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- YPMPTULBFPFSEQ-PLNGDYQASA-N ethyl (z)-3-aminobut-2-enoate Chemical compound CCOC(=O)\C=C(\C)N YPMPTULBFPFSEQ-PLNGDYQASA-N 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- XKORCTIIRYKLLG-ARJAWSKDSA-N methyl (z)-3-aminobut-2-enoate Chemical compound COC(=O)\C=C(\C)N XKORCTIIRYKLLG-ARJAWSKDSA-N 0.000 description 4
- 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 4
- 239000000725 suspension Substances 0.000 description 4
- NMTUHPSKJJYGML-UHFFFAOYSA-N 3-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=CC(C=O)=C1 NMTUHPSKJJYGML-UHFFFAOYSA-N 0.000 description 3
- CZIUQCNZBDHCHZ-UHFFFAOYSA-N 5-acetyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid Chemical compound CC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC([N+]([O-])=O)=C1 CZIUQCNZBDHCHZ-UHFFFAOYSA-N 0.000 description 3
- JPXPPUOCSLMCHK-UHFFFAOYSA-N 5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid Chemical compound COC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC([N+]([O-])=O)=C1 JPXPPUOCSLMCHK-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-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
- 241000699670 Mus sp. Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 210000001367 artery Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 230000017531 blood circulation Effects 0.000 description 3
- 239000002026 chloroform extract Substances 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- 230000010412 perfusion Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- QGMRQYFBGABWDR-UHFFFAOYSA-N sodium;5-ethyl-5-pentan-2-yl-1,3-diazinane-2,4,6-trione Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)NC1=O QGMRQYFBGABWDR-UHFFFAOYSA-N 0.000 description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 3
- FIKSTEJLLVFRJJ-UHFFFAOYSA-N 1,2,6-trimethyl-4-(3-nitrophenyl)-4h-pyridine-3,5-dicarboxylic acid Chemical compound OC(=O)C1=C(C)N(C)C(C)=C(C(O)=O)C1C1=CC=CC([N+]([O-])=O)=C1 FIKSTEJLLVFRJJ-UHFFFAOYSA-N 0.000 description 2
- RMZQSAMHIQBMLW-UHFFFAOYSA-N 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid Chemical compound OC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC=C1[N+]([O-])=O RMZQSAMHIQBMLW-UHFFFAOYSA-N 0.000 description 2
- ZGDIGQLFOVNBBC-UHFFFAOYSA-N 2,6-dimethyl-4-[2-(trifluoromethyl)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(F)(F)F ZGDIGQLFOVNBBC-UHFFFAOYSA-N 0.000 description 2
- ZDVRPKUWYQVVDX-UHFFFAOYSA-N 2-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=CC=C1C=O ZDVRPKUWYQVVDX-UHFFFAOYSA-N 0.000 description 2
- OSLAYKKXCYSJSF-UHFFFAOYSA-N 4-aminopent-3-en-2-one Chemical compound CC(N)=CC(C)=O OSLAYKKXCYSJSF-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- RXSKDKQCBUWMOP-UHFFFAOYSA-N OC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC(C(F)(F)F)=C1 Chemical compound OC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC(C(F)(F)F)=C1 RXSKDKQCBUWMOP-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
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
- 229960004373 acetylcholine Drugs 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000007059 acute toxicity Effects 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- WDIHJSXYQDMJHN-UHFFFAOYSA-L barium chloride Chemical compound [Cl-].[Cl-].[Ba+2] WDIHJSXYQDMJHN-UHFFFAOYSA-L 0.000 description 2
- 229910001626 barium chloride Inorganic materials 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229960001340 histamine Drugs 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- LYUBYLJQOZIBQB-UHFFFAOYSA-N methyl 2-[(3-nitrophenyl)methylidene]-3-oxobutanoate Chemical compound COC(=O)C(C(C)=O)=CC1=CC=CC([N+]([O-])=O)=C1 LYUBYLJQOZIBQB-UHFFFAOYSA-N 0.000 description 2
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 229960001412 pentobarbital Drugs 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical class C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- QQEOWRHUXVDVJC-UHFFFAOYSA-N 2,6-dimethyl-4-(3-nitrophenyl)-5-propan-2-yloxycarbonyl-1,4-dihydropyridine-3-carboxylic acid Chemical compound CC(C)OC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC([N+]([O-])=O)=C1 QQEOWRHUXVDVJC-UHFFFAOYSA-N 0.000 description 1
- QXLGUWJCTSGSDB-UHFFFAOYSA-N 2-[(3-nitrophenyl)methylidene]-3-oxobutanoic acid Chemical compound CC(=O)C(C(O)=O)=CC1=CC=CC([N+]([O-])=O)=C1 QXLGUWJCTSGSDB-UHFFFAOYSA-N 0.000 description 1
- UECDKJVOYBYWQP-BENRWUELSA-N 2-[benzyl(methyl)amino]ethyl (z)-3-aminobut-2-enoate Chemical compound C/C(N)=C/C(=O)OCCN(C)CC1=CC=CC=C1 UECDKJVOYBYWQP-BENRWUELSA-N 0.000 description 1
- CMWKITSNTDAEDT-UHFFFAOYSA-N 2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC=C1C=O CMWKITSNTDAEDT-UHFFFAOYSA-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
- OBNOGRJRAMNQNQ-UHFFFAOYSA-N 3-o-(2-chloroethyl) 5-o-propan-2-yl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CC(C)OC(=O)C1=C(C)NC(C)=C(C(=O)OCCCl)C1C1=CC=CC([N+]([O-])=O)=C1 OBNOGRJRAMNQNQ-UHFFFAOYSA-N 0.000 description 1
- MPOOHAOWKYTUQT-UHFFFAOYSA-N 5-ethoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC([N+]([O-])=O)=C1 MPOOHAOWKYTUQT-UHFFFAOYSA-N 0.000 description 1
- XBCXYLCYVGNHQQ-UHFFFAOYSA-N 5-methoxycarbonyl-2,6-dimethyl-4-[3-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylic acid Chemical compound COC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC(C(F)(F)F)=C1 XBCXYLCYVGNHQQ-UHFFFAOYSA-N 0.000 description 1
- UWNSXVUAQKBXIP-UHFFFAOYSA-N C1(=CC=CC=C1)N1C(=C(CC(=C1C)C(=O)O)C(=O)O)C Chemical compound C1(=CC=CC=C1)N1C(=C(CC(=C1C)C(=O)O)C(=O)O)C UWNSXVUAQKBXIP-UHFFFAOYSA-N 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- SHIYKHFFMRDJJC-UHFFFAOYSA-L [Na+].[Na+].[O-]O[O-] Chemical compound [Na+].[Na+].[O-]O[O-] SHIYKHFFMRDJJC-UHFFFAOYSA-L 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 229940045511 barium chloride Drugs 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 210000001168 carotid artery common Anatomy 0.000 description 1
- 210000001627 cerebral artery Anatomy 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- HGAZMNJKRQFZKS-UHFFFAOYSA-N chloroethene;ethenyl acetate Chemical compound ClC=C.CC(=O)OC=C HGAZMNJKRQFZKS-UHFFFAOYSA-N 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 125000004177 diethyl group Chemical class [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- PUSKHXMZPOMNTQ-UHFFFAOYSA-N ethyl 2,1,3-benzoselenadiazole-5-carboxylate Chemical compound CCOC(=O)C1=CC=C2N=[Se]=NC2=C1 PUSKHXMZPOMNTQ-UHFFFAOYSA-N 0.000 description 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- NIQQIJXGUZVEBB-UHFFFAOYSA-N methanol;propan-2-one Chemical compound OC.CC(C)=O NIQQIJXGUZVEBB-UHFFFAOYSA-N 0.000 description 1
- GKSMNBZFSFFBDM-UHFFFAOYSA-N methyl 5-(3-nitrophenyl)-3-oxopent-4-enoate Chemical compound COC(=O)CC(=O)C=CC1=CC=CC([N+]([O-])=O)=C1 GKSMNBZFSFFBDM-UHFFFAOYSA-N 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000003170 musculotropic effect Effects 0.000 description 1
- HVAAHUDGWQAAOJ-UHFFFAOYSA-N n-benzylethanamine Chemical compound CCNCC1=CC=CC=C1 HVAAHUDGWQAAOJ-UHFFFAOYSA-N 0.000 description 1
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 238000010626 work up procedure 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (16)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP48020423A JPS5930704B2 (ja) | 1973-02-20 | 1973-02-20 | 新規１，４−ジヒドロピリジン誘導体の製法 |
| JP2042373 | 1973-02-20 | ||
| JP2556673A JPS49109384A (enrdf_load_stackoverflow) | 1973-03-03 | 1973-03-03 | |
| JP2556673 | 1973-03-03 | ||
| JP4482173A JPS5714348B2 (enrdf_load_stackoverflow) | 1973-04-20 | 1973-04-20 | |
| JP4482173 | 1973-04-20 | ||
| JP5230773A JPS49135976A (enrdf_load_stackoverflow) | 1973-05-11 | 1973-05-11 | |
| JP5230773 | 1973-05-11 | ||
| JP5493973A JPS504082A (enrdf_load_stackoverflow) | 1973-05-17 | 1973-05-17 | |
| JP5493973 | 1973-05-17 | ||
| JP8327673 | 1973-07-24 | ||
| JP8327673A JPS5720950B2 (enrdf_load_stackoverflow) | 1973-07-24 | 1973-07-24 | |
| JP13406973A JPS5545075B2 (enrdf_load_stackoverflow) | 1973-11-29 | 1973-11-29 | |
| JP13407073A JPS5084577A (enrdf_load_stackoverflow) | 1973-11-29 | 1973-11-29 | |
| JP13406973 | 1973-11-29 | ||
| JP13407073 | 1973-11-29 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| FI58772B FI58772B (fi) | 1980-12-31 |
| FI58772C true FI58772C (fi) | 1981-04-10 |
Family
ID=27571887
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI446/74A FI58772C (fi) | 1973-02-20 | 1974-02-15 | Foerfarande foer framstaellning av hjaernblodaodror utvidgande 2,6-dimetyl-4-substituerad-fenyl-1,4-dihydropyridin-3-karboxylsyra-aminoalkylestrar |
Country Status (8)
| Country | Link |
|---|---|
| CA (1) | CA1023746A (enrdf_load_stackoverflow) |
| CH (1) | CH605755A5 (enrdf_load_stackoverflow) |
| DE (1) | DE2407115C3 (enrdf_load_stackoverflow) |
| DK (1) | DK142869B (enrdf_load_stackoverflow) |
| FI (1) | FI58772C (enrdf_load_stackoverflow) |
| GB (1) | GB1455502A (enrdf_load_stackoverflow) |
| NL (2) | NL176559C (enrdf_load_stackoverflow) |
| NO (1) | NO143846C (enrdf_load_stackoverflow) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK152285C (da) * | 1975-07-02 | 1988-10-10 | Fujisawa Pharmaceutical Co | Analogifremgangsmaade til fremstilling af 1,4-dihydropyridinderivater |
| JPS55301A (en) * | 1978-02-14 | 1980-01-05 | Yamanouchi Pharmaceut Co Ltd | 1,4-dihydropyridine-3,5-dicarboxylic ester derivative and its preparation |
| DE2815578C2 (de) * | 1978-04-11 | 1986-01-16 | Bayer Ag, 5090 Leverkusen | Neue pharmazeutische Verwendung von Nimodipin |
| IT1097538B (it) * | 1978-07-17 | 1985-08-31 | Medea Res Srl | Processo per la preparazione del 2,6-dimetil-4-3(3-nitrofenil)-3-metossicarbonil-1,4-didropiridin-5-carbossilati di 2(n-benzil-n-metilammino) |
| DE2949464A1 (de) * | 1978-12-18 | 1980-06-26 | Sandoz Ag | Benzoxadiazole und benzothiadiazole, ihre herstellung und verwendung |
| JPS5762257A (en) * | 1980-10-03 | 1982-04-15 | Yoshitomi Pharmaceut Ind Ltd | 1,4-dihydropyridine-3,5-dicarboxylic acid ester or its salt |
| JPS57200386A (en) * | 1981-06-04 | 1982-12-08 | Yoshitomi Pharmaceut Ind Ltd | Novel 1,4-dihydropyridine-3,5-dicarboxylic ester derivative and its salts |
| WO1983003249A1 (en) * | 1982-03-17 | 1983-09-29 | Yoshitomi Pharmaceutical | 1,4-dihydropyridine-3,5-dicarboxylate derivatives |
| ATE50987T1 (de) * | 1982-05-10 | 1990-03-15 | Takeda Chemical Industries Ltd | Dihydropyridinderivate, deren herstellung und verwendung. |
| ATE52030T1 (de) * | 1984-01-13 | 1990-05-15 | Yamanouchi Pharma Co Ltd | Arzneimittel fuer die behandlung und verhuetung von leberschaedigungen. |
| AT388375B (de) * | 1984-04-11 | 1989-06-12 | Bristol Myers Co | Verfahren zur herstellung von neuen dihydropyridincarbonsaeureamiden und -estern |
| JPS6289662A (ja) * | 1985-06-14 | 1987-04-24 | Sankyo Co Ltd | １，４−ジヒドロピリジン誘導体 |
| DE3531498A1 (de) * | 1985-09-04 | 1987-03-05 | Bayer Ag | Dihydropyridin-2-hydroxyamine, verfahren zur herstellung und ihre verwendung in arzneimitteln |
| DE3621104A1 (de) * | 1986-06-24 | 1988-01-07 | Heumann Pharma Gmbh & Co | 1,4-dihydropyridinderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| US4772596A (en) * | 1986-10-09 | 1988-09-20 | Sankyo Company Limited | Dihydropyridine derivatives, their preparation and their use |
| SI8810082A8 (en) * | 1988-01-18 | 1995-12-31 | Lek Tovarna Farmacevtskih | Process for preparing new inclusion complex of nicardipine or its hydrochloride with beta-cyclodextrine |
| NL9001752A (nl) * | 1990-08-02 | 1992-03-02 | Cedona Pharm Bv | Nieuwe 1,4-dihydropyridinederivaten. |
| WO1998049144A1 (fr) * | 1997-04-25 | 1998-11-05 | Ajinomoto Co., Inc. | Nouveau derive de dihydropyridine |
| ES2332168B1 (es) * | 2008-04-30 | 2010-10-27 | Consejo Superior De Investigaciones Cientificas (Csic) (75%) | Forma pseudopolimorfica de hidrocloruro de nicardipina, procedimiento para su preparacion y formulacion que la contiene. |
-
1974
- 1974-02-11 GB GB604574A patent/GB1455502A/en not_active Expired
- 1974-02-14 CA CA192,552A patent/CA1023746A/en not_active Expired
- 1974-02-15 CH CH212174A patent/CH605755A5/xx not_active IP Right Cessation
- 1974-02-15 DE DE2407115A patent/DE2407115C3/de not_active Expired
- 1974-02-15 FI FI446/74A patent/FI58772C/fi active
- 1974-02-19 NO NO740543A patent/NO143846C/no unknown
- 1974-02-19 NL NLAANVRAGE7402277,A patent/NL176559C/xx active Protection Beyond IP Right Term
- 1974-02-19 DK DK87774AA patent/DK142869B/da not_active IP Right Cessation
-
1993
- 1993-03-25 NL NL930023C patent/NL930023I2/nl unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CH605755A5 (enrdf_load_stackoverflow) | 1978-10-13 |
| CA1023746A (en) | 1978-01-03 |
| NL930023I2 (nl) | 1997-08-01 |
| NO740543L (no) | 1974-08-21 |
| NL930023I1 (nl) | 1993-05-17 |
| NO143846B (no) | 1981-01-12 |
| NL176559C (nl) | 1985-05-01 |
| DE2407115A1 (de) | 1974-10-10 |
| NL7402277A (enrdf_load_stackoverflow) | 1974-08-22 |
| DE2407115C3 (de) | 1980-05-08 |
| NL176559B (nl) | 1984-12-03 |
| DE2407115B2 (de) | 1979-08-09 |
| NO143846C (no) | 1981-04-29 |
| GB1455502A (en) | 1976-11-10 |
| DK142869C (enrdf_load_stackoverflow) | 1981-09-28 |
| AU6565574A (en) | 1975-08-21 |
| DK142869B (da) | 1981-02-16 |
| FI58772B (fi) | 1980-12-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| FI58772C (fi) | Foerfarande foer framstaellning av hjaernblodaodror utvidgande 2,6-dimetyl-4-substituerad-fenyl-1,4-dihydropyridin-3-karboxylsyra-aminoalkylestrar | |
| US3985758A (en) | 1,4-Dihydropyridine derivatives | |
| US4656181A (en) | Esters of 1,4-dihydropyridines, processes for the preparation of the new esters, and medicaments containing the same | |
| US4322346A (en) | 5H-2,3-Benzodiazepine derivatives | |
| KR860001921B1 (ko) | 1,4-디하이드로피리딘의 제조방법 | |
| US3708489A (en) | Azido-aryl 1,4-dihydropyridines and their production | |
| GB2158065A (en) | Dihydropyridines | |
| EP0097821B1 (en) | Dihydropyridines with an antagonistic activity to calcium, process for their preparation, and pharmaceutical compositions containing them | |
| EP0068171B1 (en) | Dihydropyridine compounds | |
| US3823152A (en) | 3-substituted-2-piperidinethiones and homologues thereof | |
| US3974275A (en) | 1,4-Dihydropyridine carboxylic acid esters useful as coronary vessel dilators and anti-hypertensives | |
| US3968117A (en) | 1,4-Dihydropyridines | |
| JPS62175462A (ja) | 置換１，４−ジヒドロピリジン−３−カルボン酸ピペラジド類 | |
| US4004014A (en) | 2-Amino-6-dialkylaminodihydropyridines, their production, pharmaceutical compositions and methods of use thereof | |
| US4166855A (en) | 1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid ester, and its use as a peripheral vasodilator | |
| NO139130B (no) | Fremgangsmaate til fremstilling av 2-alkylamino-dihydropyridiner | |
| US4364952A (en) | Certain 1,4-dihydro-2,6-dimethyl-3,5-pyridine-dicarboxylates, composition containing same and method of use | |
| KR900004923B1 (ko) | 1,4-디히드로피리딘 유도체의 제조방법 | |
| JP2640245B2 (ja) | １，４−ジヒドロピリジン誘導体 | |
| US4038399A (en) | 1,4-dihydropyridine carboxylic acid esters useful as coronary vessel dilators and anti-hypertensives | |
| US4742068A (en) | Dihydropyridine compounds having 1,4,4-trisubstitution useful as antihypertensive agents | |
| EP0264232A1 (en) | 2-Azetidinone derivatives | |
| US4963554A (en) | 6,7-dimethoxy-1,2-dihydro-2-arylquinazoline-3-oxides | |
| US2663710A (en) | Series of nitrofuran compounds comprising 5-nitro-2-furyl 2-dialkyl-aminoalkyl ketone semicarbazone salts | |
| JPS5916876A (ja) | カルシウムに拮抗する塩基性エステル、その製造法およびそれを有効成分とする医薬 |