FI101377B - Menetelmä N-alkyloitujen 1,4-dihydropyridiiniyhdisteiden valmistamisek si - Google Patents
Menetelmä N-alkyloitujen 1,4-dihydropyridiiniyhdisteiden valmistamisek si Download PDFInfo
- Publication number
- FI101377B FI101377B FI911700A FI911700A FI101377B FI 101377 B FI101377 B FI 101377B FI 911700 A FI911700 A FI 911700A FI 911700 A FI911700 A FI 911700A FI 101377 B FI101377 B FI 101377B
- Authority
- FI
- Finland
- Prior art keywords
- methyl
- formula
- general formula
- dihydropyridine
- ester
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 27
- 230000008569 process Effects 0.000 title claims abstract description 16
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical class C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 title claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
- 150000001875 compounds Chemical class 0.000 claims description 28
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- -1 benzylidene compound Chemical class 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 150000002148 esters Chemical class 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 150000001298 alcohols Chemical class 0.000 claims description 5
- 239000007858 starting material Substances 0.000 claims description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- OIORMXXUKIGDHC-UHFFFAOYSA-N diethyl 1-cyclopropyl-2,6-dimethyl-4-[4-(trifluoromethyl)phenyl]-4h-pyridine-3,5-dicarboxylate Chemical compound CC1=C(C(=O)OCC)C(C=2C=CC(=CC=2)C(F)(F)F)C(C(=O)OCC)=C(C)N1C1CC1 OIORMXXUKIGDHC-UHFFFAOYSA-N 0.000 claims description 4
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 4
- 239000012442 inert solvent Substances 0.000 claims description 4
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 claims description 3
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 229910021529 ammonia Inorganic materials 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 239000012467 final product Substances 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 claims 2
- 239000002841 Lewis acid Substances 0.000 claims 1
- UNQWSIBNMPYECZ-UHFFFAOYSA-N dimethyl 1,2-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C=1CNC=C(C=1)C(=O)OC UNQWSIBNMPYECZ-UHFFFAOYSA-N 0.000 claims 1
- 150000007517 lewis acids Chemical class 0.000 claims 1
- 230000000302 ischemic effect Effects 0.000 abstract description 7
- 230000001154 acute effect Effects 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 4
- 230000004089 microcirculation Effects 0.000 abstract description 4
- SYHPGXUWPYJXOO-UHFFFAOYSA-N 1,4-dihydropyridine-2,3-dicarboxylic acid Chemical class OC(=O)C1=C(C(O)=O)NC=CC1 SYHPGXUWPYJXOO-UHFFFAOYSA-N 0.000 abstract description 3
- 239000013543 active substance Substances 0.000 abstract description 2
- 230000002490 cerebral effect Effects 0.000 abstract description 2
- 230000002792 vascular Effects 0.000 abstract description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 2
- 230000001684 chronic effect Effects 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
- 239000002547 new drug Substances 0.000 abstract 1
- 230000002093 peripheral effect Effects 0.000 abstract 1
- 210000003743 erythrocyte Anatomy 0.000 description 15
- 238000012360 testing method Methods 0.000 description 11
- 230000036772 blood pressure Effects 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 239000011575 calcium Substances 0.000 description 9
- 229910052791 calcium Inorganic materials 0.000 description 9
- 230000017531 blood circulation Effects 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 230000037396 body weight Effects 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- AVFYPHPSIBAAME-UHFFFAOYSA-N dimethyl 1,2,6-trimethyl-4-[4-(trifluoromethyl)phenyl]-4h-pyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)N(C)C(C)=C(C(=O)OC)C1C1=CC=C(C(F)(F)F)C=C1 AVFYPHPSIBAAME-UHFFFAOYSA-N 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 208000023589 ischemic disease Diseases 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000002587 anti-hemolytic effect Effects 0.000 description 3
- 230000003276 anti-hypertensive effect Effects 0.000 description 3
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 3
- 230000010221 calcium permeability Effects 0.000 description 3
- 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 238000010253 intravenous injection Methods 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 239000011148 porous material Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- BEOBZEOPTQQELP-UHFFFAOYSA-N 4-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=C(C=O)C=C1 BEOBZEOPTQQELP-UHFFFAOYSA-N 0.000 description 2
- 108091006112 ATPases Proteins 0.000 description 2
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 108010054147 Hemoglobins Proteins 0.000 description 2
- 102000001554 Hemoglobins Human genes 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 241000700157 Rattus norvegicus Species 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 230000004087 circulation Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- GYWPWUWXZRKZQL-UHFFFAOYSA-N dimethyl 4-(4-bromophenyl)-1,2,6-trimethyl-4h-pyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)N(C)C(C)=C(C(=O)OC)C1C1=CC=C(Br)C=C1 GYWPWUWXZRKZQL-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 2
- PBMIETCUUSQZCG-UHFFFAOYSA-N n'-cyclohexylmethanediimine Chemical compound N=C=NC1CCCCC1 PBMIETCUUSQZCG-UHFFFAOYSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 238000000638 solvent extraction Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 239000010936 titanium Substances 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
- 210000003462 vein Anatomy 0.000 description 2
- UKVYVZLTGQVOPX-IHWYPQMZSA-N (z)-3-aminobut-2-enoic acid Chemical class C\C(N)=C\C(O)=O UKVYVZLTGQVOPX-IHWYPQMZSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 1
- JDXQWYKOKYUQDN-UHFFFAOYSA-N 3-hydroxypyrrolidine-2,5-dione Chemical class OC1CC(=O)NC1=O JDXQWYKOKYUQDN-UHFFFAOYSA-N 0.000 description 1
- MBHWPWGNLACPPI-UHFFFAOYSA-N 4-(4-fluorophenyl)-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=C(F)C=C1 MBHWPWGNLACPPI-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- 206010022562 Intermittent claudication Diseases 0.000 description 1
- 238000005684 Liebig rearrangement reaction Methods 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 101100463797 Rattus norvegicus Pgrmc1 gene Proteins 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229910003074 TiCl4 Inorganic materials 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- GCPWJFKTWGFEHH-UHFFFAOYSA-N acetoacetamide Chemical compound CC(=O)CC(N)=O GCPWJFKTWGFEHH-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000002253 anti-ischaemic effect Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000001201 calcium accumulation Effects 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001722 carbon compounds Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 150000008050 dialkyl sulfates Chemical class 0.000 description 1
- HZCKGIURZKOEOL-UHFFFAOYSA-N diethyl 1,2,6-trimethyl-4-[4-(trifluoromethyl)phenyl]-4h-pyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)N(C)C(C)=C(C(=O)OCC)C1C1=CC=C(C(F)(F)F)C=C1 HZCKGIURZKOEOL-UHFFFAOYSA-N 0.000 description 1
- JRBHSUIZKASZRG-UHFFFAOYSA-N diethyl 4-(4-fluorophenyl)-1,2,6-trimethyl-4h-pyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)N(C)C(C)=C(C(=O)OCC)C1C1=CC=C(F)C=C1 JRBHSUIZKASZRG-UHFFFAOYSA-N 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000001206 effect on leukocytes Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- FARYTWBWLZAXNK-WAYWQWQTSA-N ethyl (z)-3-(methylamino)but-2-enoate Chemical compound CCOC(=O)\C=C(\C)NC FARYTWBWLZAXNK-WAYWQWQTSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 108010036302 hemoglobin AS Proteins 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 150000007928 imidazolide derivatives Chemical class 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 229910001502 inorganic halide Inorganic materials 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 208000021156 intermittent vascular claudication Diseases 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 230000003836 peripheral circulation Effects 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- AAHLDRPWGQIXIE-SREVYHEPSA-N propyl (z)-3-(methylamino)but-2-enoate Chemical compound CCCOC(=O)\C=C(\C)NC AAHLDRPWGQIXIE-SREVYHEPSA-N 0.000 description 1
- HNFCWFPZYSJCMI-UHFFFAOYSA-N propyl 3-(4-bromophenyl)prop-2-enoate Chemical compound CCCOC(=O)C=CC1=CC=C(Br)C=C1 HNFCWFPZYSJCMI-UHFFFAOYSA-N 0.000 description 1
- PWZUUYSISTUNDW-VAFBSOEGSA-N quinestrol Chemical compound C([C@@H]1[C@@H](C2=CC=3)CC[C@]4([C@H]1CC[C@@]4(O)C#C)C)CC2=CC=3OC1CCCC1 PWZUUYSISTUNDW-VAFBSOEGSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 150000003459 sulfonic acid esters Chemical class 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- CMJCEVKJYRZMIA-UHFFFAOYSA-M thallium(i) iodide Chemical compound [Tl]I CMJCEVKJYRZMIA-UHFFFAOYSA-M 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Epidemiology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Lubricants (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4011695A DE4011695A1 (de) | 1990-04-11 | 1990-04-11 | Verwendung von n-alkylierten 1,4-dihydropyridindicarbonsaeureestern als arzneimittel, neue verbindungen und verfahren zu ihrer herstellung |
| DE4011695 | 1990-04-11 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI911700A0 FI911700A0 (fi) | 1991-04-09 |
| FI911700A7 FI911700A7 (fi) | 1991-10-12 |
| FI101377B1 FI101377B1 (fi) | 1998-06-15 |
| FI101377B true FI101377B (fi) | 1998-06-15 |
Family
ID=6404197
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI911700A FI101377B (fi) | 1990-04-11 | 1991-04-09 | Menetelmä N-alkyloitujen 1,4-dihydropyridiiniyhdisteiden valmistamisek si |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US5234935A (cg-RX-API-DMAC10.html) |
| EP (1) | EP0451654B1 (cg-RX-API-DMAC10.html) |
| JP (1) | JP3012352B2 (cg-RX-API-DMAC10.html) |
| KR (1) | KR0180741B1 (cg-RX-API-DMAC10.html) |
| AT (1) | ATE111079T1 (cg-RX-API-DMAC10.html) |
| AU (1) | AU642992B2 (cg-RX-API-DMAC10.html) |
| CA (1) | CA2040062A1 (cg-RX-API-DMAC10.html) |
| DE (2) | DE4011695A1 (cg-RX-API-DMAC10.html) |
| DK (1) | DK0451654T3 (cg-RX-API-DMAC10.html) |
| ES (1) | ES2063998T3 (cg-RX-API-DMAC10.html) |
| FI (1) | FI101377B (cg-RX-API-DMAC10.html) |
| HU (2) | HUT59905A (cg-RX-API-DMAC10.html) |
| IE (1) | IE64452B1 (cg-RX-API-DMAC10.html) |
| IL (1) | IL97796A (cg-RX-API-DMAC10.html) |
| NZ (1) | NZ237722A (cg-RX-API-DMAC10.html) |
| PT (1) | PT97300B (cg-RX-API-DMAC10.html) |
| TW (1) | TW197423B (cg-RX-API-DMAC10.html) |
| ZA (1) | ZA912652B (cg-RX-API-DMAC10.html) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4342196A1 (de) * | 1993-12-10 | 1995-06-14 | Bayer Ag | Neue 4-Phenyl-substituierte 1,4-Dihydropyridine |
| DE4125271A1 (de) * | 1991-07-31 | 1993-02-11 | Bayer Ag | Neue n-alkylierte 1,4-dihydropyridindicarbonsaeureester |
| WO1993006082A1 (en) * | 1991-09-13 | 1993-04-01 | Merck & Co., Inc. | Process for the preparation of 4-substituted-1,4-dihydropyridines |
| US5310917A (en) * | 1991-09-13 | 1994-05-10 | Merck & Co., Inc. | Process for the preparation of 4-substituted-1,4-dihydropydrines |
| DE4133257A1 (de) * | 1991-10-08 | 1993-04-15 | Bayer Ag | N-methyl-nimodipin, verfahren zu seiner herstellung und seine verwendung als zerebraltherapeutikum |
| DE4200714A1 (de) * | 1992-01-14 | 1993-07-15 | Bayer Ag | Spezieller 1,4-dihydropyridin-3,5-dicarbonsaeureester, verfahren zu seiner herstellung und seine pharmazeutische verwendung |
| DE4223867A1 (de) * | 1992-07-20 | 1994-01-27 | Bayer Ag | Spezieller 1,4-Dihydropyridin-3,5-dicarbonsäureester, Verfahren zu seiner Herstellung und seine pharmazeutische Verwendung |
| DE4313691A1 (de) * | 1993-04-27 | 1994-11-03 | Bayer Ag | 2,6-Disubstituierte 4-Chinolyl-dihydropyridine |
| DE4313692A1 (de) * | 1993-04-27 | 1994-11-03 | Bayer Ag | 3-Chinolyl substituierte Dihydropyridine, Verfahren zu ihrer Herstellung und ihre Verwendung in Arzneimitteln |
| DE4313697A1 (de) * | 1993-04-27 | 1994-11-03 | Bayer Ag | Chinolyl-dihydropyridinester, Verfahren zu ihrer Herstellung und ihre Verwendung in Arzneimitteln |
| DE4328884A1 (de) * | 1993-08-27 | 1995-03-02 | Bayer Ag | Verwendung von N-alkylierten 1,4-Dihydropyridincarbonsäureestern als Arzneimittel |
| EP0657432B1 (de) * | 1993-12-10 | 2003-03-12 | Bayer Ag | Phenyl-substituierte 1,4-Dihydropyridine mit cerebraler Aktivität |
| EE03192B1 (et) * | 1993-12-10 | 1999-06-15 | Bayer Aktiengesellschaft | Isopropüül-(2-metoksüetüül)-4-(2-kloro-3-tsüanofenüül)-1,4-dihüdro-2,6-dimetüülpüri diin-3,5-dikarboksülaat, selle enantiomeerid ja vaheühend, meetodid nimetatud ühendite valmistamiseks ja kasutamine |
| DE4430094A1 (de) | 1994-08-25 | 1996-02-29 | Bayer Ag | Verwendung von 3,5-Dicarbonsäureester-1,4-Dihydropyridinen als Arzneimittel |
| DE19638570A1 (de) * | 1996-09-20 | 1998-03-26 | Bayer Ag | Wirkstoffhaltige thermoplastische Polyurethane |
| AU2002361992A1 (en) * | 2001-12-20 | 2003-07-09 | Bayer Aktiengesellschaft | 1,4-dihydro-1,4-diphenylpyridine derivatives |
| US8420790B2 (en) | 2009-10-30 | 2013-04-16 | Reliable Biopharmaceutical Corporation | Efficient and scalable process for the manufacture of Fondaparinux sodium |
| CA2854252C (en) * | 2011-11-24 | 2016-11-29 | Lipidart Kutato Fejleszto Es Tanacsado Kft. | 1,4-dihydropyridine derivatives with hsp modulating activity |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1813436C3 (de) * | 1968-12-07 | 1979-01-11 | Bayer Ag, 5090 Leverkusen | N-Substituierte 2,6-Dimethyl-l,4dihydropyridine |
| US3883543A (en) * | 1969-05-10 | 1975-05-13 | Bayer Ag | N-alkyl-1,4-dihydropyridines |
| DE1923990C3 (de) * | 1969-05-10 | 1978-11-23 | Bayer Ag | Verfahren zur Herstellung von N-substituierten M-Dihydropyridin-S.S-dicarbonsäureestern |
| DE1963188A1 (de) * | 1969-12-17 | 1971-06-24 | Bayer Ag | Neue Cyanphenyl-1,4-dihydropyridinderivate |
| CH550189A (de) * | 1971-01-08 | 1974-06-14 | Ciba Geigy Ag | Verfahren zur herstellung von neuen dibenzo (b,f) thiepincarbonsaeuren. |
| DE2210667A1 (de) * | 1972-03-06 | 1973-09-20 | Bayer Ag | Kondensiert aromatisch substituierte 1,4-dihydropyridine, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel |
| DE2210672C3 (de) * | 1972-03-06 | 1980-03-20 | Bayer Ag, 5090 Leverkusen | N-substituierte unsymmetrische 1 ^-Dihydropyridin-S^-dicarbonsäureester, Verfahren zu ihrer Herstellung sowie ihre Verwendung als Arzneimittel |
| DE2228377A1 (de) * | 1972-06-10 | 1974-01-03 | Bayer Ag | Dihydropyridin-carbonsaeureamide, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel |
| CH569043A5 (cg-RX-API-DMAC10.html) * | 1973-01-23 | 1975-11-14 | Ciba Geigy Ag | |
| US3956341A (en) * | 1974-02-21 | 1976-05-11 | Smithkline Corporation | 1,3,5-Tricarbo-1,4-dihydropyridines |
| SU798099A1 (ru) * | 1978-03-06 | 1981-01-23 | Ордена Трудового Красного Знамениинститут Органического Синтезаан Латвийской Ccp | 1-Бензил-2,6-диметил-4-о-или-M-НиТРОфЕНил-3,5-диэТОКСиКАРбОНил- 1,4-дигидРОпиРидиНы, пРО Вл ющиЕКОРОНАРОдилАТиРующую АКТиВНОСТь |
| EP0176956B1 (de) * | 1984-09-28 | 1994-06-15 | Byk Gulden Lomberg Chemische Fabrik GmbH | Neue Diarylverbindungen |
| US4975440A (en) * | 1984-09-28 | 1990-12-04 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Optically-active 1,4-dihydropyridine |
| US4780538A (en) * | 1986-02-12 | 1988-10-25 | Merck & Co., Inc. | Process for 1,4-dihydropyridine compounds using a titanamine catalyst |
| GB8616047D0 (en) * | 1986-07-01 | 1986-08-06 | Sandoz Ltd | A 1 4-dihydropyridine derivatives |
| GR1002248B (en) * | 1988-03-08 | 1996-04-23 | Egyt Gyogyszervegyeszeti Gyar | 1,4-dihydropyridine derivatives preparation method |
-
1990
- 1990-04-11 DE DE4011695A patent/DE4011695A1/de not_active Withdrawn
-
1991
- 1991-03-30 ES ES91105115T patent/ES2063998T3/es not_active Expired - Lifetime
- 1991-03-30 AT AT91105115T patent/ATE111079T1/de active
- 1991-03-30 DK DK91105115.9T patent/DK0451654T3/da active
- 1991-03-30 EP EP91105115A patent/EP0451654B1/de not_active Expired - Lifetime
- 1991-03-30 DE DE59102788T patent/DE59102788D1/de not_active Expired - Fee Related
- 1991-04-04 US US07/680,454 patent/US5234935A/en not_active Expired - Fee Related
- 1991-04-08 JP JP3101762A patent/JP3012352B2/ja not_active Expired - Lifetime
- 1991-04-08 CA CA002040062A patent/CA2040062A1/en not_active Abandoned
- 1991-04-08 NZ NZ237722A patent/NZ237722A/en unknown
- 1991-04-08 IL IL9779691A patent/IL97796A/en not_active IP Right Cessation
- 1991-04-09 AU AU74253/91A patent/AU642992B2/en not_active Ceased
- 1991-04-09 FI FI911700A patent/FI101377B/fi active
- 1991-04-09 PT PT97300A patent/PT97300B/pt not_active IP Right Cessation
- 1991-04-10 TW TW080102712A patent/TW197423B/zh active
- 1991-04-10 ZA ZA912652A patent/ZA912652B/xx unknown
- 1991-04-10 IE IE120091A patent/IE64452B1/en not_active IP Right Cessation
- 1991-04-10 KR KR1019910005710A patent/KR0180741B1/ko not_active Expired - Fee Related
- 1991-04-11 HU HU911184A patent/HUT59905A/hu unknown
-
1993
- 1993-05-21 US US08/065,503 patent/US5432185A/en not_active Expired - Fee Related
-
1995
- 1995-06-22 HU HU95P/P00334P patent/HU211313A9/hu unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ES2063998T3 (es) | 1995-01-16 |
| AU642992B2 (en) | 1993-11-04 |
| DE59102788D1 (de) | 1994-10-13 |
| US5432185A (en) | 1995-07-11 |
| FI101377B1 (fi) | 1998-06-15 |
| TW197423B (cg-RX-API-DMAC10.html) | 1993-01-01 |
| PT97300B (pt) | 1998-10-30 |
| JPH04234847A (ja) | 1992-08-24 |
| KR910018025A (ko) | 1991-11-30 |
| EP0451654A3 (en) | 1992-07-08 |
| EP0451654A2 (de) | 1991-10-16 |
| PT97300A (pt) | 1992-01-31 |
| ZA912652B (en) | 1992-01-29 |
| CA2040062A1 (en) | 1991-10-12 |
| US5234935A (en) | 1993-08-10 |
| IL97796A (en) | 1995-03-15 |
| KR0180741B1 (ko) | 1999-03-20 |
| HUT59905A (en) | 1992-07-28 |
| IE64452B1 (en) | 1995-08-09 |
| HU211313A9 (en) | 1995-11-28 |
| HU911184D0 (en) | 1991-10-28 |
| AU7425391A (en) | 1991-10-17 |
| EP0451654B1 (de) | 1994-09-07 |
| FI911700A0 (fi) | 1991-04-09 |
| JP3012352B2 (ja) | 2000-02-21 |
| DE4011695A1 (de) | 1991-10-17 |
| ATE111079T1 (de) | 1994-09-15 |
| FI911700A7 (fi) | 1991-10-12 |
| NZ237722A (en) | 1995-10-26 |
| DK0451654T3 (da) | 1995-02-13 |
| IE911200A1 (en) | 1991-10-23 |
| IL97796A0 (en) | 1992-06-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5237332B2 (ja) | ジヒドロピリミジン類 | |
| KR0180741B1 (ko) | 약제로서 n-알킬화 1,4-디히드로피리딘디카르복실산 에스테르의 용도, 신규 화합물 및 그의 제조 방법 | |
| FI91634C (fi) | Menetelmä terapeuttisesti käyttökelpoisten 1,4-dihydropyridiinijohdannaisten valmistamiseksi | |
| OA12648A (en) | Novel crystalline polymorphic forms of lercanidipine hydrochloride and process for their preparation. | |
| HU192406B (en) | Process for preparing 1,4-dihydro-pyridine derivatives and pharmaceutical compositions containing such compounds | |
| HU204786B (en) | Process for producing new dihydropyridine amide derivatives and pharmaceutical compositions comprising such compounds | |
| IL102032A (en) | 2-amino-5-cyano-1,4-dihydropyridines their preparation and pharmaceutical compositions containing them | |
| AU616057B2 (en) | Use of basic nitro-phenyl-dihydropyridine amides as medicaments, new compounds and processes for their preparation via new intermediates | |
| US5262429A (en) | Aryl-quinolyl-substituted 1,4-dihydropyridine-dicarboxylic acid compounds which have useful pharmaceutical utility | |
| JPS6289662A (ja) | １，４−ジヒドロピリジン誘導体 | |
| US5342847A (en) | Specific 1,4-dihydropyridine-3,5-dicarboxylic acid ester and its pharmaceutical use | |
| HUT52055A (en) | Process for producing basic 4-aryl-dihydropyridin-amides and pharmaceutical compositions containing them | |
| FI85491B (fi) | Foerfarande foer framstaellning av nya terapeutiskt anvaendbara fosfonsyraderivat. | |
| JPS6112663A (ja) | 光学的に活性な１，４‐ジヒドロピリジン類の製造方法 | |
| CN1105102C (zh) | 氨基丁烯酸酯化合物及其制备方法 | |
| SK158095A3 (en) | Application of 1,2-bridged 1,4-dihydropyridines, 1,2-bridged 1,4-dihydropyridines, manufacturing process thereof and pharmaceutical compositions containing them | |
| JPH07215965A (ja) | インドールスルホンアミド−置換ジヒドロピリジン類 | |
| HU197304B (en) | Process for producing fluor-containing 1,4-dihydro-pyridines and pharmaceutical compositions containing them | |
| FI63022B (fi) | Foerfarande foer framstaellning av vasodilatoriska 1,4-dihydropyridinderivat | |
| NZ250085A (en) | Use of dihydropyridinedicarboxylic acid esters as pharmaceuticals | |
| JPH0253774A (ja) | １，４―ジヒドロピリジン―スレオニン誘導体 | |
| JPH0527624B2 (cg-RX-API-DMAC10.html) | ||
| JPH072774A (ja) | ジヒドロピリジン誘導体、その製造法、該誘導体を含有する医薬組成物および高血圧症の治療薬の製造を目的とする該誘導体の使用方法 | |
| JPS63264459A (ja) | 新規な１，４−ジヒドロピリジン誘導体及びその製造法 | |
| EP0370821A2 (en) | 1,4-dihydropyridine derivatives |