FI70573C - Analogifoerfarande foer framstaellning av terapeutiskt aktiv 2,6-dimetyl-4-(2,3-diklorfenyl)-1,4-dihydro- pyridin-3,5-dikarboxylsyra-3-metylester-5-etylester - Google Patents
Analogifoerfarande foer framstaellning av terapeutiskt aktiv 2,6-dimetyl-4-(2,3-diklorfenyl)-1,4-dihydro- pyridin-3,5-dikarboxylsyra-3-metylester-5-etylester Download PDFInfo
- Publication number
- FI70573C FI70573C FI792058A FI792058A FI70573C FI 70573 C FI70573 C FI 70573C FI 792058 A FI792058 A FI 792058A FI 792058 A FI792058 A FI 792058A FI 70573 C FI70573 C FI 70573C
- Authority
- FI
- Finland
- Prior art keywords
- sub
- formula
- compound
- formulation
- dimethyl
- Prior art date
Links
- -1 2,3-DICHLOROPHENYL Chemical class 0.000 title abstract description 14
- 230000001225 therapeutic effect Effects 0.000 title description 5
- 230000004913 activation Effects 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 54
- 238000000034 method Methods 0.000 claims abstract description 21
- 238000002360 preparation method Methods 0.000 claims abstract description 15
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 7
- 239000000203 mixture Substances 0.000 claims description 23
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 20
- 238000009472 formulation Methods 0.000 claims description 17
- RZTAMFZIAATZDJ-UHFFFAOYSA-N felodipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-UHFFFAOYSA-N 0.000 claims description 14
- 229910021529 ammonia Inorganic materials 0.000 claims description 9
- 230000003287 optical effect Effects 0.000 claims description 9
- 238000000638 solvent extraction Methods 0.000 claims description 2
- 230000003276 anti-hypertensive effect Effects 0.000 abstract description 6
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract description 3
- 125000001309 chloro group Chemical group Cl* 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 230000000694 effects Effects 0.000 description 16
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 14
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000000126 substance Substances 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 238000002425 crystallisation Methods 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- LHAOQTPGTBGTIG-UHFFFAOYSA-N 4-(2,3-dichlorophenyl)-5-methoxycarbonyl-2,6-dimethyl-1,4-dihydropyridine-3-carboxylic acid Chemical compound COC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC(Cl)=C1Cl LHAOQTPGTBGTIG-UHFFFAOYSA-N 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 230000008025 crystallization Effects 0.000 description 7
- 230000002093 peripheral effect Effects 0.000 description 7
- 230000002107 myocardial effect Effects 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 239000013543 active substance Substances 0.000 description 5
- 230000036772 blood pressure Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical compound COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 description 4
- 208000037849 arterial hypertension Diseases 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 210000003205 muscle Anatomy 0.000 description 4
- 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 4
- 239000003208 petroleum Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 206010020772 Hypertension Diseases 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- RRKTZKIUPZVBMF-IBTVXLQLSA-N brucine Chemical compound O([C@@H]1[C@H]([C@H]2C3)[C@@H]4N(C(C1)=O)C=1C=C(C(=CC=11)OC)OC)CC=C2CN2[C@@H]3[C@]41CC2 RRKTZKIUPZVBMF-IBTVXLQLSA-N 0.000 description 3
- YPMPTULBFPFSEQ-PLNGDYQASA-N ethyl (z)-3-aminobut-2-enoate Chemical compound CCOC(=O)\C=C(\C)N YPMPTULBFPFSEQ-PLNGDYQASA-N 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 229960001597 nifedipine Drugs 0.000 description 3
- 210000002460 smooth muscle Anatomy 0.000 description 3
- 230000024883 vasodilation Effects 0.000 description 3
- LLMLNAVBOAMOEE-UHFFFAOYSA-N 2,3-dichlorobenzaldehyde Chemical compound ClC1=CC=CC(C=O)=C1Cl LLMLNAVBOAMOEE-UHFFFAOYSA-N 0.000 description 2
- GCUMHOAQJSSYSV-UHFFFAOYSA-N 4-(2,3-dichlorophenyl)-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(Cl)=C1Cl GCUMHOAQJSSYSV-UHFFFAOYSA-N 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical class ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 206010033799 Paralysis Diseases 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000002249 anxiolytic agent Substances 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- RRKTZKIUPZVBMF-UHFFFAOYSA-N brucine Natural products C1=2C=C(OC)C(OC)=CC=2N(C(C2)=O)C3C(C4C5)C2OCC=C4CN2C5C31CC2 RRKTZKIUPZVBMF-UHFFFAOYSA-N 0.000 description 2
- 210000000748 cardiovascular system Anatomy 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 2
- 230000001631 hypertensive effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 210000002464 muscle smooth vascular Anatomy 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 210000003240 portal vein Anatomy 0.000 description 2
- 230000002040 relaxant effect Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- AAWZDTNXLSGCEK-LNVDRNJUSA-N (3r,5r)-1,3,4,5-tetrahydroxycyclohexane-1-carboxylic acid Chemical compound O[C@@H]1CC(O)(C(O)=O)C[C@@H](O)C1O AAWZDTNXLSGCEK-LNVDRNJUSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- GDQLHKHFHWLXES-UHFFFAOYSA-N 1,5-dichlorocyclohexa-2,4-diene-1-carbaldehyde Chemical compound ClC1=CC=CC(Cl)(C=O)C1 GDQLHKHFHWLXES-UHFFFAOYSA-N 0.000 description 1
- LNSCNEJNLACZPA-UHFFFAOYSA-N 2,3-dihydroxy-2,3-bis(2-methylphenyl)butanedioic acid Chemical compound CC1=CC=CC=C1C(O)(C(O)=O)C(O)(C(O)=O)C1=CC=CC=C1C LNSCNEJNLACZPA-UHFFFAOYSA-N 0.000 description 1
- PNWUMZKKOVXVIK-UHFFFAOYSA-N 3-o-ethyl 5-o-(2-methoxyethyl) 4-(2-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCCOC)C1C1=CC=CC=C1Cl PNWUMZKKOVXVIK-UHFFFAOYSA-N 0.000 description 1
- UFBVEBSZOZXYBE-UHFFFAOYSA-N 4-(2-chlorophenyl)-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=C1Cl UFBVEBSZOZXYBE-UHFFFAOYSA-N 0.000 description 1
- LAJSHCJZMXWQAG-UHFFFAOYSA-N COC(=O)CC(=O)C=CC1(CC(=CC=C1)Cl)Cl Chemical compound COC(=O)CC(=O)C=CC1(CC(=CC=C1)Cl)Cl LAJSHCJZMXWQAG-UHFFFAOYSA-N 0.000 description 1
- LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- AAWZDTNXLSGCEK-UHFFFAOYSA-N Cordycepinsaeure Natural products OC1CC(O)(C(O)=O)CC(O)C1O AAWZDTNXLSGCEK-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 206010021118 Hypotonia Diseases 0.000 description 1
- 206010049816 Muscle tightness Diseases 0.000 description 1
- 206010069140 Myocardial depression Diseases 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- RYXPMWYHEBGTRV-UHFFFAOYSA-N Omeprazole sodium Chemical compound [Na+].N=1C2=CC(OC)=CC=C2[N-]C=1S(=O)CC1=NC=C(C)C(OC)=C1C RYXPMWYHEBGTRV-UHFFFAOYSA-N 0.000 description 1
- 241000036848 Porzana carolina Species 0.000 description 1
- AAWZDTNXLSGCEK-ZHQZDSKASA-N Quinic acid Natural products O[C@H]1CC(O)(C(O)=O)C[C@H](O)C1O AAWZDTNXLSGCEK-ZHQZDSKASA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 241000084978 Rena Species 0.000 description 1
- UZHDGDDPOPDJGM-UHFFFAOYSA-N Stigmatellin A Natural products COC1=CC(OC)=C2C(=O)C(C)=C(CCC(C)C(OC)C(C)C(C=CC=CC(C)=CC)OC)OC2=C1O UZHDGDDPOPDJGM-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- ABRVLXLNVJHDRQ-UHFFFAOYSA-N [2-pyridin-3-yl-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound FC(C1=CC(=CC(=N1)C=1C=NC=CC=1)CN)(F)F ABRVLXLNVJHDRQ-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 210000000702 aorta abdominal Anatomy 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000000571 coke Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000037020 contractile activity Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 125000004188 dichlorophenyl group Chemical group 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 239000003085 diluting agent Substances 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
- 230000004064 dysfunction Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000010247 heart contraction Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- BUMNIEQNRVFXLA-UHFFFAOYSA-N methyl 5-(2,3-dichlorophenyl)-3-oxopent-4-enoate Chemical compound COC(=O)CC(=O)C=CC1=CC=CC(Cl)=C1Cl BUMNIEQNRVFXLA-UHFFFAOYSA-N 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 230000036640 muscle relaxation Effects 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 210000002346 musculoskeletal system Anatomy 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000050 smooth muscle relaxant Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- ZXUCBXRTRRIBSO-UHFFFAOYSA-L tetrabutylazanium;sulfate Chemical compound [O-]S([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC.CCCC[N+](CCCC)(CCCC)CCCC ZXUCBXRTRRIBSO-UHFFFAOYSA-L 0.000 description 1
- 238000002627 tracheal intubation Methods 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- 238000010792 warming 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
- 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
- A61P9/12—Antihypertensives
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Heart & Thoracic Surgery (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Steroid Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE7807404A SE429652B (sv) | 1978-06-30 | 1978-06-30 | 2.6-dimetyl-4-(2.3-diklorfenyl)-1.4-dihydropyridin-3.5-dikarboxylsyra-3-metylester-5-etylester |
| SE7807404 | 1978-06-30 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI792058A7 FI792058A7 (fi) | 1979-12-31 |
| FI70573B FI70573B (fi) | 1986-06-06 |
| FI70573C true FI70573C (fi) | 1986-09-24 |
Family
ID=20335348
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI792058A FI70573C (fi) | 1978-06-30 | 1979-06-29 | Analogifoerfarande foer framstaellning av terapeutiskt aktiv 2,6-dimetyl-4-(2,3-diklorfenyl)-1,4-dihydro- pyridin-3,5-dikarboxylsyra-3-metylester-5-etylester |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US4264611A (enExample) |
| EP (1) | EP0007293B1 (enExample) |
| JP (1) | JPS559083A (enExample) |
| AT (1) | ATE1237T1 (enExample) |
| AU (1) | AU529116B2 (enExample) |
| BG (1) | BG61420B2 (enExample) |
| CA (1) | CA1117530A (enExample) |
| CS (1) | CS241021B2 (enExample) |
| CY (1) | CY1299A (enExample) |
| DD (1) | DD144667A5 (enExample) |
| DE (1) | DE2963150D1 (enExample) |
| DK (1) | DK148978C (enExample) |
| FI (1) | FI70573C (enExample) |
| HK (1) | HK60585A (enExample) |
| HU (1) | HU178568B (enExample) |
| IE (1) | IE48650B1 (enExample) |
| LU (2) | LU88666I2 (enExample) |
| NL (2) | NL930054I2 (enExample) |
| NO (3) | NO151965C (enExample) |
| NZ (1) | NZ190809A (enExample) |
| SE (1) | SE429652B (enExample) |
| SG (1) | SG26085G (enExample) |
| SU (2) | SU856380A3 (enExample) |
| ZA (1) | ZA792804B (enExample) |
Families Citing this family (61)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2935451A1 (de) * | 1979-09-01 | 1981-03-19 | Bayer Ag, 5090 Leverkusen | Optisch aktive 1,4-dihydropyridine, verfahren zu ihrer herstellung und ihre verwendung als arneimittel |
| SE7910521L (sv) * | 1979-12-20 | 1981-06-21 | Haessle Ab | Nya 2-metyl-6-substituerade-4-(2,3-disubstituerad fenyl)-1,4-dihydropyridin-3,5-diestrar med hypotesiva egenskaper, samt forfarande for deras framstellning, och farmaceutiska beredningar innehallande desamma |
| IL68604A0 (en) * | 1982-05-21 | 1983-09-30 | Haessle Ab | Processes for preparing therapeutically active dihydropyridines and intermediates for the processes |
| US4656181A (en) * | 1982-11-24 | 1987-04-07 | Cermol S.A. | Esters of 1,4-dihydropyridines, processes for the preparation of the new esters, and medicaments containing the same |
| DE3307422A1 (de) * | 1983-03-03 | 1984-09-06 | Bayer Ag, 5090 Leverkusen | Fluessigzubereitungen von dihydropyridinen, ein verfahren zu ihrer herstellung, sowie ihre verwendung bei der bekaempfung von erkrankungen |
| AU561213B2 (en) * | 1983-06-02 | 1987-04-30 | Teijin Limited | 1, 4-dihydropyridine derivative |
| DE3339236A1 (de) * | 1983-10-28 | 1985-05-09 | Bayer Ag | Arzneimittelzubereitung |
| DE4342196A1 (de) * | 1993-12-10 | 1995-06-14 | Bayer Ag | Neue 4-Phenyl-substituierte 1,4-Dihydropyridine |
| IE57810B1 (en) * | 1984-03-27 | 1993-04-21 | Delagrange Lab | 1,4-dihydropyridine derivatives,their preparation and their use |
| FI852359A7 (fi) * | 1984-06-27 | 1985-12-28 | F Hoffmann La Roche & Co | Dihydropyridiinijohdannaisia. |
| US4757071A (en) * | 1984-12-14 | 1988-07-12 | Nisshin Flour Milling Co., Ltd. | 1,4-dihydropyridine derivatives, and pharmaceutical compositions containing same, useful for treating cardiovascular diseases |
| DE3447169A1 (de) * | 1984-12-22 | 1986-07-03 | Bayer Ag, 5090 Leverkusen | Optisch aktive nitrodihydropyridine, verfahren zur herstellung und ihre verwendung in arzneimitteln |
| DE3447170A1 (de) * | 1984-12-22 | 1986-07-03 | Bayer Ag, 5090 Leverkusen | Mischung unterschiedlicher dihydropyridine, verfahren zu ihrer herstellung sowie ihre verwendung in arzneimitteln |
| NZ220022A (en) * | 1986-04-22 | 1990-04-26 | Byk Gulden Lomberg Chem Fab | 1,4-dihydropyridine derivatives and pharmaceutical compositions |
| US4920225A (en) * | 1986-12-22 | 1990-04-24 | Laboratoires Syntex S.A. | Resolution of 1,4-dihydropyridine derivatives |
| JPS63255071A (ja) * | 1987-04-14 | 1988-10-21 | 株式会社 岡田吾作郎商店 | 磁石内蔵健康棒 |
| AT391269B (de) * | 1988-12-30 | 1990-09-10 | Burghart Kurt | Pharmazeutische zubereitung |
| US5310917A (en) * | 1991-09-13 | 1994-05-10 | Merck & Co., Inc. | Process for the preparation of 4-substituted-1,4-dihydropydrines |
| US5834496A (en) * | 1991-12-02 | 1998-11-10 | Sepracor, Inc. | Methods for treating hypertension using optically pure S(-) felodipine |
| WO1993010781A1 (en) * | 1991-12-02 | 1993-06-10 | Sepracor, Inc. | Methods and compositions for treating hypertension, angina, and other disorders using optically pure s(-) felodipine |
| EP0657432B1 (de) * | 1993-12-10 | 2003-03-12 | Bayer Ag | Phenyl-substituierte 1,4-Dihydropyridine mit cerebraler Aktivität |
| DE4430639A1 (de) * | 1994-08-29 | 1996-03-07 | Bayer Ag | Verwendung von 5-substituierten Pyridin- und Hexahydrochinolin-3-carbonsäurederivaten |
| TW483763B (en) * | 1994-09-02 | 2002-04-21 | Astra Ab | Pharmaceutical composition comprising of ramipril and dihydropyridine compound |
| US5977369A (en) * | 1995-12-28 | 1999-11-02 | Napp Technologies, Inc. | Process to prepare dihydropyridine and derivatives thereof |
| SE9600086D0 (sv) * | 1996-01-10 | 1996-01-10 | Astra Ab | New manufacturing process |
| IT1283793B1 (it) * | 1996-08-23 | 1998-04-30 | Lusochimica Spa | Processo per la preparazione di diidropiridine |
| WO2000005209A1 (fr) * | 1998-07-23 | 2000-02-03 | Lin, Tong-Ho | GUAIACOXYPROPANOLAMINES A ACTIVITE α/β-ADRENOLYTIQUE |
| US6555139B2 (en) | 1999-06-28 | 2003-04-29 | Wockhardt Europe Limited | Preparation of micron-size pharmaceutical particles by microfluidization |
| US6569456B2 (en) | 2000-01-13 | 2003-05-27 | Osmotica Corp. | Osmotic device containing diltiazem and an ACE inhibitor or diuretic |
| BR0109991A (pt) * | 2000-04-11 | 2003-05-27 | Sankyo Co | Composição farmacêutica |
| US6653481B2 (en) * | 2000-12-29 | 2003-11-25 | Synthon Bv | Process for making amlodipine |
| EP2316468A1 (en) | 2002-02-22 | 2011-05-04 | Shire LLC | Delivery system and methods for protecting and administering dextroamphetamine |
| EA200500234A1 (ru) | 2002-08-19 | 2005-08-25 | Пфайзер Продактс Инк. | Комбинированная терапия гиперпролиферативных болезней |
| SG141430A1 (en) * | 2003-05-30 | 2008-04-28 | Ranbaxy Lab Ltd | Substituted pyrrole derivatives and their use as hmg-co inhibitors |
| US20050037063A1 (en) * | 2003-07-21 | 2005-02-17 | Bolton Anthony E. | Combined therapies |
| CA2574958A1 (en) * | 2004-07-26 | 2006-02-09 | Cotherix, Inc. | Treatment of pulmonary hypertension by inhaled iloprost with a microparticle formulation |
| 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 |
| WO2007050783A2 (en) | 2005-10-26 | 2007-05-03 | Asahi Kasei Pharma Corporation | Fasudil in combination therapies for the treatment of pulmonary arterial hypertension |
| BRPI0618379A2 (pt) * | 2005-11-08 | 2011-08-30 | Ranbaxy Lab Ltd | processo para preparação do hemi-sal de cálcio do ácido (3r,5r) -7-[2-(4-fluorofenil)-5-isopropil-3-fenil-4-[(4-hidroxime tilfenilamino) carbonil]-pirrol-1-il] -3, 5-diidroxi heptanóico |
| US7888376B2 (en) | 2005-11-23 | 2011-02-15 | Bristol-Myers Squibb Company | Heterocyclic CETP inhibitors |
| TW200806648A (en) * | 2005-11-29 | 2008-02-01 | Sankyo Co | Acid addition salts of dihydropyridine derivatives |
| TW200736245A (en) * | 2005-11-29 | 2007-10-01 | Sankyo Co | Acid addition salts of optically active dihydropyridine derivatives |
| US7919506B2 (en) | 2006-03-10 | 2011-04-05 | Pfizer Inc. | Dibenzyl amine compounds and derivatives |
| AR059838A1 (es) * | 2006-03-14 | 2008-04-30 | Ranbaxy Lab Ltd | Formulaciones para dosis estabilizantes de estatina |
| AU2007274724B2 (en) * | 2006-07-14 | 2012-07-26 | Ranbaxy Laboratories Limited | Polymorphic forms of an HMG-CoA reductase inhibitor and uses thereof |
| 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 |
| US8748648B2 (en) | 2007-09-06 | 2014-06-10 | Nektar Therapeutics | Oligomer-calcium channel blocker conjugates |
| CA2705097A1 (en) * | 2007-11-07 | 2009-05-14 | Janssen Pharmaceutica N.V. | Combination therapy comprising angiotensin converting enzyme inhibitors and vasopressin receptor antagonists |
| 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 |
| WO2012123966A1 (en) | 2011-03-04 | 2012-09-20 | Arch Pharmalabs Limited | Process for the preparation of 4 -substituted -1, 4-dihydropyridines |
| CN102827068A (zh) * | 2011-06-17 | 2012-12-19 | 张锐豪 | 一种4-(2, 3-二氯苯基)-2, 6-二甲基-1, 4-二氢-5-甲氧基羰基-3-吡啶羧酸的制备方法 |
| KR101708538B1 (ko) | 2011-08-26 | 2017-02-20 | 욱크하르트 리미티드 | 심혈관 질환의 치료 방법 |
| CN105143203A (zh) | 2013-04-17 | 2015-12-09 | 辉瑞大药厂 | 用于治疗心血管疾病的n-哌啶-3-基苯甲酰胺衍生物 |
| CN104177286A (zh) * | 2014-08-11 | 2014-12-03 | 广东东阳光药业有限公司 | 一种地平类药物的制备方法 |
| WO2016055901A1 (en) | 2014-10-08 | 2016-04-14 | Pfizer Inc. | Substituted amide compounds |
| KR101824982B1 (ko) | 2015-10-07 | 2018-02-02 | 엘지전자 주식회사 | 차량 및 그 제어방법 |
| CN107952483B (zh) * | 2017-12-18 | 2020-07-28 | 万华化学集团股份有限公司 | 一种催化剂，使用该催化剂的反应器，以及一种制备β-苯乙醇的方法 |
| CN108840819B (zh) * | 2018-04-02 | 2021-07-30 | 常州瑞明药业有限公司 | 一种非洛地平的制备方法 |
| CN112955965B (zh) | 2018-06-14 | 2024-04-09 | 阿斯利康(英国)有限公司 | 使用二氢吡啶类钙通道阻断剂医药组合物降低血压的方法 |
| WO2020150473A2 (en) | 2019-01-18 | 2020-07-23 | Dogma Therapeutics, Inc. | Pcsk9 inhibitors and methods of use thereof |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3441648A (en) * | 1967-02-07 | 1969-04-29 | Smithkline Corp | Compositions and methods for lowering blood pressure with 1,4-dihydropyridines |
| DE1670824C3 (de) * | 1967-03-20 | 1978-08-03 | Bayer Ag, 5090 Leverkusen | 1,4-Dihydropyridin-33-dicarbonsäurealkylester |
| DE2117572C3 (de) * | 1971-04-10 | 1980-03-20 | Bayer Ag, 5090 Leverkusen | Unsymmetrische 1,4-Dihydropyridin ^-dicarbonsäureester, Verfahren zu ihrer Herstellung sowie ihre Verwendung als Arzneimittel |
| DE2117573C3 (de) * | 1971-04-10 | 1978-07-27 | Bayer Ag, 5090 Leverkusen | Verfahren zur Herstellung von unsymmetrischen l,4-Dihydropyridin-3,5dicarbonsäureestern, sowie ihre Verwendung als Arzneimittel |
| DE2117571C3 (de) * | 1971-04-10 | 1979-10-11 | Bayer Ag, 5090 Leverkusen | Unsymmetrische 1,4-Dihydropyridin-33-dicarbonsäureester, 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 |
| GB1552911A (en) * | 1975-07-02 | 1979-09-19 | Fujisawa Pharmaceutical Co | 1,4 dihydropyridine derivatives and the preparation thereof |
-
1978
- 1978-06-30 SE SE7807404A patent/SE429652B/sv unknown
-
1979
- 1979-06-06 ZA ZA792804A patent/ZA792804B/xx unknown
- 1979-06-12 LU LU88666C patent/LU88666I2/fr unknown
- 1979-06-12 DE DE7979850057T patent/DE2963150D1/de not_active Expired
- 1979-06-12 EP EP79850057A patent/EP0007293B1/en not_active Expired
- 1979-06-12 CY CY1299A patent/CY1299A/xx unknown
- 1979-06-12 AT AT79850057T patent/ATE1237T1/de active
- 1979-06-19 US US06/050,083 patent/US4264611A/en not_active Expired - Lifetime
- 1979-06-22 NO NO792112A patent/NO151965C/no unknown
- 1979-06-22 AU AU48316/79A patent/AU529116B2/en not_active Expired
- 1979-06-25 NZ NZ190809A patent/NZ190809A/xx unknown
- 1979-06-28 CA CA000330762A patent/CA1117530A/en not_active Expired
- 1979-06-28 DD DD79213967A patent/DD144667A5/de unknown
- 1979-06-29 DK DK275079A patent/DK148978C/da active
- 1979-06-29 SU SU792781817A patent/SU856380A3/ru active
- 1979-06-29 CS CS794585A patent/CS241021B2/cs unknown
- 1979-06-29 FI FI792058A patent/FI70573C/fi not_active IP Right Cessation
- 1979-06-29 HU HU79HE788A patent/HU178568B/hu unknown
- 1979-06-30 JP JP8206279A patent/JPS559083A/ja active Granted
- 1979-08-08 IE IE1217/79A patent/IE48650B1/en not_active IP Right Cessation
-
1980
- 1980-05-15 SU SU802921246A patent/SU915799A3/ru active
-
1985
- 1985-04-06 SG SG260/85A patent/SG26085G/en unknown
- 1985-08-15 HK HK605/85A patent/HK60585A/en not_active IP Right Cessation
-
1993
- 1993-06-10 NL NL930054C patent/NL930054I2/nl unknown
- 1993-06-16 LU LU88306C patent/LU88306I2/fr unknown
-
1994
- 1994-02-25 BG BG098595A patent/BG61420B2/bg unknown
- 1994-06-29 NL NL940012C patent/NL940012I1/nl unknown
- 1994-12-21 NO NO1994026C patent/NO1994026I1/no unknown
-
1996
- 1996-06-24 NO NO1996006C patent/NO1996006I1/no unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| FI70573B (fi) | Analogifoerfarande foer framstaellning av terapeutiskt aktiv 2,6-dimetyl-4-2,3-diklorfenyl-1,4-dihydro- pyridin-3,5-dikarboxsylsyra-3-metylester-5-etylester | |
| FI90543C (fi) | Menetelmä lääkeaineina käyttökelpoisten dihydropyridiinin johdannaisten valmistamiseksi | |
| FR2615191A1 (fr) | Nouveaux benzo(b)pyrannes et pyrannopyridines, leur preparation et leur utilisation comme medicaments | |
| FI86425B (fi) | Foerfarande foer framstaellning av terapeutiskt aktiva 6-benzoxazinyl- och 6-benzotiazinyl-2,3,4,5- tetrahydropyridazin-3-oner. | |
| US4472411A (en) | 1,4-Dihydropyridine derivatives and use as vasodilators | |
| JPS63297365A (ja) | ジヒドロピリジン類 | |
| FR2562892A1 (fr) | Nouveaux dihydropyridinyldicarboxylates amides et esters, utilisation de ces composes comme medicament, compositions pharmaceutiques comprenant de tels composes et procede pour la preparation de tels composes | |
| EP0300865A1 (fr) | Dérivés de N-aminobutyl N-phényl arylamides, leur préparation et leur application en thérapeutique | |
| EP0446141A1 (fr) | Nouveaux dérivés d'imidazo [1,2-C] quinazoline leur procédé de préparation et les compositions pharmaceutiques les renfermant | |
| US4576934A (en) | Antihypertensive dihydropyridine-5-phosphonic acid cyclic esters | |
| US4782069A (en) | 1,4-Dihydropiridines and their use as antithrombotic drugs | |
| AU628995B2 (en) | Novel thienopyran derivatives, a process for their preparation and their use | |
| SK48094A3 (en) | Condensated chinolyl-dihydropyridines, method of their production, treatments containing these matters, method of production and using of these compounds | |
| EP0136198A1 (fr) | Dérivés de triazolo pyrimidine, leur procédé de préparation et leur application thérapeutique en tant que toni-cardiaques | |
| KR900005956B1 (ko) | 1,4-디하이드로피리딘-3,5-디카르복실산의 비대칭 에스테르 유도체의 제조방법 | |
| FR2596051A1 (fr) | Nouveaux derives de la purine, leur preparation et leur utilisation comme medicaments | |
| SK158692A3 (en) | 2-amino-5-cyano-1,4-dihydropyridines, method of their preparation and their use in medicines | |
| SU1731049A3 (ru) | Способ получени симметричного эфира 4-замещенной 1,4-дигидропиридин-3,5-дикарбоновой кислоты или его физиологически приемлемых солей | |
| Taylor et al. | 2-(2-Aryl-2-oxoethylidene)-1, 2, 3, 4-tetrahydropyridines. Novel isomers of 1, 4-dihydropyridine calcium channel blockers | |
| JPS62174050A (ja) | ３−アミノカルボニル−１，４−ジヒドロピリジン−５−カルボン酸誘導体、その製法および医薬組成物 | |
| US4280998A (en) | 1,4-Dihydropyridazine-3-carboxylic acid derivatives, a process for their preparation and their use as antihypertensives | |
| CH679859A5 (enExample) | ||
| CA1205471A (en) | Dihydropyridines | |
| RU2155751C2 (ru) | Производные 1,4-дигидропиридина, смесь их изомеров или отдельные изомеры, фармацевтическая композиция на их основе и 2-хлор-3-цианобензальдегид | |
| FI85491B (fi) | Foerfarande foer framstaellning av nya terapeutiskt anvaendbara fosfonsyraderivat. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MA | Patent expired | ||
| SPCG | Supplementary protection certificate granted |
Spc suppl protection certif: L82 Extension date: 20030121 |
|
| ND | Supplementary protection certificate (spc) granted | ||
| ND | Supplementary protection certificate (spc) granted | ||
| SPCG | Supplementary protection certificate granted |
Spc suppl protection certif: L98 Extension date: 20040629 |
|
| MA | Patent expired |
Owner name: AKTIEBOLAGET HAESSLE |