PH27052A - Biologically active molecules - Google Patents
Biologically active molecules Download PDFInfo
- Publication number
- PH27052A PH27052A PH34991A PH34991A PH27052A PH 27052 A PH27052 A PH 27052A PH 34991 A PH34991 A PH 34991A PH 34991 A PH34991 A PH 34991A PH 27052 A PH27052 A PH 27052A
- Authority
- PH
- Philippines
- Prior art keywords
- alkyl
- aryl
- chy
- substituted
- methyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims description 76
- -1 piperazinvl Chemical class 0.000 claims description 73
- 125000000217 alkyl group Chemical group 0.000 claims description 53
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 47
- 229910052739 hydrogen Inorganic materials 0.000 claims description 37
- 239000001257 hydrogen Substances 0.000 claims description 36
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 35
- 125000003118 aryl group Chemical group 0.000 claims description 33
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 31
- 239000002253 acid Substances 0.000 claims description 27
- 150000002431 hydrogen Chemical group 0.000 claims description 25
- 125000003545 alkoxy group Chemical group 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- 125000004414 alkyl thio group Chemical group 0.000 claims description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 13
- 239000001301 oxygen Substances 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 229910052717 sulfur Chemical group 0.000 claims description 12
- 239000011593 sulfur Chemical group 0.000 claims description 12
- 125000001475 halogen functional group Chemical group 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- PZQSQRCNMZGWFT-QXMHVHEDSA-N propan-2-yl (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC(C)C PZQSQRCNMZGWFT-QXMHVHEDSA-N 0.000 claims description 6
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 6
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 230000003185 calcium uptake Effects 0.000 claims description 5
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 5
- 125000001261 isocyanato group Chemical group *N=C=O 0.000 claims description 5
- 125000001810 isothiocyanato group Chemical group *N=C=S 0.000 claims description 5
- 229940124549 vasodilator Drugs 0.000 claims description 5
- 239000003071 vasodilator agent Substances 0.000 claims description 5
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 230000000903 blocking effect Effects 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 125000001188 haloalkyl group Chemical group 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 150000003973 alkyl amines Chemical class 0.000 claims description 2
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 6
- 201000010099 disease Diseases 0.000 claims 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 4
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims 2
- 240000002390 Pandanus odoratissimus Species 0.000 claims 1
- 235000005311 Pandanus odoratissimus Nutrition 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 150000002540 isothiocyanates Chemical class 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 125000004193 piperazinyl group Chemical group 0.000 claims 1
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 200
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 156
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 93
- 238000006243 chemical reaction Methods 0.000 description 80
- 150000002148 esters Chemical class 0.000 description 75
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 70
- 239000000243 solution Substances 0.000 description 67
- 239000000203 mixture Substances 0.000 description 59
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 58
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 51
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 48
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 45
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 44
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 43
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 43
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 41
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- 229910052786 argon Inorganic materials 0.000 description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
- 238000003756 stirring Methods 0.000 description 33
- 238000002844 melting Methods 0.000 description 32
- 230000008018 melting Effects 0.000 description 32
- 229960000443 hydrochloric acid Drugs 0.000 description 28
- 235000011167 hydrochloric acid Nutrition 0.000 description 28
- 239000000047 product Substances 0.000 description 27
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 26
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 25
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 25
- 238000004809 thin layer chromatography Methods 0.000 description 25
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- 239000007787 solid Substances 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
- 238000004458 analytical method Methods 0.000 description 23
- 239000013078 crystal Substances 0.000 description 23
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 21
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 20
- 235000019341 magnesium sulphate Nutrition 0.000 description 20
- 239000006260 foam Substances 0.000 description 19
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
- 229940086542 triethylamine Drugs 0.000 description 17
- 235000017557 sodium bicarbonate Nutrition 0.000 description 16
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 16
- 239000012074 organic phase Substances 0.000 description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 14
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 14
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 14
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 13
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 11
- 125000004494 ethyl ester group Chemical group 0.000 description 11
- 238000003818 flash chromatography Methods 0.000 description 11
- 229910000027 potassium carbonate Inorganic materials 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 10
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 10
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 10
- 238000002425 crystallisation Methods 0.000 description 10
- 230000008025 crystallization Effects 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 7
- IIVUJUOJERNGQX-UHFFFAOYSA-N pyrimidine-5-carboxylic acid Chemical compound OC(=O)C1=CN=CN=C1 IIVUJUOJERNGQX-UHFFFAOYSA-N 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 6
- AYMUACMNMRHMLH-UHFFFAOYSA-N 2-methoxy-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyrimidine-5-carboxylic acid Chemical compound OC(=O)C1=C(C)NC(OC)=NC1C1=CC=CC([N+]([O-])=O)=C1 AYMUACMNMRHMLH-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- AVGAIPMGSIOHFZ-UHFFFAOYSA-N dichloromethane;2-propan-2-yloxypropane Chemical compound ClCCl.CC(C)OC(C)C AVGAIPMGSIOHFZ-UHFFFAOYSA-N 0.000 description 6
- 125000005843 halogen group Chemical group 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 239000000377 silicon dioxide Substances 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- MDFRYRPNRLLJHT-UHFFFAOYSA-N methyl carbamimidate;sulfuric acid Chemical compound COC(N)=N.OS(O)(=O)=O MDFRYRPNRLLJHT-UHFFFAOYSA-N 0.000 description 5
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 5
- 239000001632 sodium acetate Substances 0.000 description 5
- 235000017281 sodium acetate Nutrition 0.000 description 5
- MSLUAJQVSKPJHS-UHFFFAOYSA-N 3-carbamoyl-6-methyl-4-(3-nitrophenyl)-2-oxo-1,4-dihydropyrimidine-5-carboxylic acid Chemical compound NC(=O)N1C(=O)NC(C)=C(C(O)=O)C1C1=CC=CC([N+]([O-])=O)=C1 MSLUAJQVSKPJHS-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 4
- 125000002619 bicyclic group Chemical group 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- 239000012452 mother liquor Substances 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- NXLNNXIXOYSCMB-UHFFFAOYSA-N (4-nitrophenyl) carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(OC(Cl)=O)C=C1 NXLNNXIXOYSCMB-UHFFFAOYSA-N 0.000 description 3
- AGZMCPABUCGMFU-UHFFFAOYSA-N 3-(dimethylcarbamoyl)-6-methyl-4-(3-nitrophenyl)-2-oxo-1,4-dihydropyrimidine-5-carboxylic acid Chemical compound OC(=O)C1=C(C)NC(=O)N(C(=O)N(C)C)C1C1=CC=CC([N+]([O-])=O)=C1 AGZMCPABUCGMFU-UHFFFAOYSA-N 0.000 description 3
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 239000002220 antihypertensive agent Substances 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- 150000003385 sodium Chemical class 0.000 description 3
- 238000001665 trituration Methods 0.000 description 3
- 239000003039 volatile agent Substances 0.000 description 3
- UAAIKSGKUWSAKU-UHFFFAOYSA-N 2-[(4-methoxyphenyl)methylsulfanyl]-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyrimidine-5-carboxylic acid Chemical compound C1=CC(OC)=CC=C1CSC1=NC(C=2C=C(C=CC=2)[N+]([O-])=O)C(C(O)=O)=C(C)N1 UAAIKSGKUWSAKU-UHFFFAOYSA-N 0.000 description 2
- FLFDXXPIDMBYET-UHFFFAOYSA-N 4-(2,1,3-benzoxadiazol-4-yl)-2-methoxy-6-methyl-1,4-dihydropyrimidine-5-carboxylic acid Chemical compound OC(=O)C1=C(C)NC(OC)=NC1C1=CC=CC2=NON=C12 FLFDXXPIDMBYET-UHFFFAOYSA-N 0.000 description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- JZGMBSXAOIURKR-UHFFFAOYSA-N 4-methyl-6-(3-nitrophenyl)pyrimidine-5-carboxylic acid Chemical compound CC1=C(C(=NC=N1)C1=CC(=CC=C1)[N+](=O)[O-])C(=O)O JZGMBSXAOIURKR-UHFFFAOYSA-N 0.000 description 2
- 239000005541 ACE inhibitor Substances 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 229930194542 Keto Natural products 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 description 2
- QGNMUFKTLKVUHM-UHFFFAOYSA-N [c-[(4-methoxyphenyl)methylsulfanyl]carbonimidoyl]azanium;chloride Chemical compound [Cl-].COC1=CC=C(CSC([NH3+])=N)C=C1 QGNMUFKTLKVUHM-UHFFFAOYSA-N 0.000 description 2
- 239000000464 adrenergic agent Substances 0.000 description 2
- 150000001447 alkali salts Chemical class 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 2
- 239000003416 antiarrhythmic agent Substances 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
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- A—HUMAN NECESSITIES
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US83976786A | 1986-03-14 | 1986-03-14 | |
| US91734986A | 1986-10-09 | 1986-10-09 | |
| US07/008,037 US4855301A (en) | 1986-10-09 | 1987-02-09 | 1,2,3,4-Tetrahydro-6-substituted-4-aryl(or heterocyclo)-3-((substituted amino)carbonyl)-2-thioxo (or oxo)-5-pyrimidinecarboxylic acids and esters |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PH27052A true PH27052A (en) | 1993-02-01 |
Family
ID=27358497
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PH34991A PH27052A (en) | 1986-03-14 | 1987-03-06 | Biologically active molecules |
Country Status (17)
| Country | Link |
|---|---|
| EP (1) | EP0237347B1 (da) |
| JP (1) | JPH0819113B2 (da) |
| KR (1) | KR900005014B1 (da) |
| CA (1) | CA1337655C (da) |
| DE (1) | DE3770661D1 (da) |
| DK (1) | DK169031B1 (da) |
| ES (1) | ES2039234T3 (da) |
| FI (1) | FI96683C (da) |
| GR (1) | GR3002715T3 (da) |
| HU (1) | HU206091B (da) |
| IE (1) | IE60114B1 (da) |
| IL (1) | IL81800A0 (da) |
| NO (1) | NO871044L (da) |
| PH (1) | PH27052A (da) |
| PL (1) | PL153727B1 (da) |
| PT (1) | PT84479B (da) |
| SU (1) | SU1713437A3 (da) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62267272A (ja) * | 1986-05-15 | 1987-11-19 | Sanwa Kagaku Kenkyusho Co Ltd | 新規なジヒドロピリミジン化合物及びその塩、これらの製法並びに該化合物を有効成分とする循環器系作用剤 |
| US4847379A (en) * | 1987-11-30 | 1989-07-11 | E. R. Squibb & Sons, Inc. | 3,6-dihydro-1,5(2H)-pyrimidinecarboxylic acid esters |
| CN1173132A (zh) | 1994-11-16 | 1998-02-11 | 辛纳普蒂克制药公司 | 二氢嘧啶类化合物及其用途 |
| US6268369B1 (en) | 1994-11-16 | 2001-07-31 | Synaptic Pharmaceutical Corporation | 5-(heterocyclic alkyl)-6-aryl-dihydropyrimidines |
| JP2000500470A (ja) * | 1995-11-16 | 2000-01-18 | シナプティック・ファーマスーティカル・コーポレーション | ジヒドロピリミジンおよびその使用 |
| US6228861B1 (en) | 1995-11-16 | 2001-05-08 | Synaptic Pharmaceutical Corporation | Dihydropyrimidines and uses thereof |
| US6172066B1 (en) | 1996-05-16 | 2001-01-09 | Synaptic Pharmaceutical Corporation | Dihydropyrimidines and uses thereof |
| US6245773B1 (en) | 1996-05-16 | 2001-06-12 | Synaptic Pharmaceutical Corporation | 5-(heterocyclic alkyl)-6-aryl-dihydropyrimidines |
| EP0986553A4 (en) * | 1997-02-04 | 2000-12-27 | Bristol Myers Squibb Co | DIHYDROPYRIMIDONE DERIVATIVES AS NPY ANTAGONISTS |
| US6680323B2 (en) | 1998-12-23 | 2004-01-20 | Synaptic Pharmaceutical Corporation | Dihydropyrimidines and uses thereof |
| US6274585B1 (en) | 1998-12-23 | 2001-08-14 | Synaptic Pharmaceutical Corporation | Dihydropyrimidines and uses thereof |
| EP1193259A4 (en) * | 1999-06-23 | 2003-01-29 | Ajinomoto Kk | dihydropyrimidine |
| US6720324B2 (en) | 2000-07-05 | 2004-04-13 | Synaptic Pharmaceutical Corporation | Selective melanin concentrating hormone-1 (MCH1) receptor antagonists and uses thereof |
| CA2498282C (en) * | 2002-09-12 | 2012-07-10 | Diakron Pharmaceuticals, Inc. | Calcium channel blockers |
| US7157461B2 (en) | 2003-07-23 | 2007-01-02 | Bristol-Myers Squibb Co. | Substituted dihydropyrimidine inhibitors of calcium channel function |
| US7166603B2 (en) | 2003-07-23 | 2007-01-23 | Bristol-Myers Squibb Co. | Dihydropyrimidone inhibitors of calcium channel function |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60214778A (ja) * | 1984-03-08 | 1985-10-28 | Suntory Ltd | Ν置換３，４−ジヒドロピリミジン誘導体ならびにその製造法および用途 |
| HUT42077A (en) * | 1985-06-03 | 1987-06-29 | Squibb & Sons Inc | Process for producing diesters of 2-tioxo- or 2-oxo-pyrimidine-1,5-dicarboxylic acid and 1-acyl-pyrimidine-5-carboxylic acids and esters |
| US4675321A (en) * | 1986-02-07 | 1987-06-23 | Merck & Co., Inc. | Substituted pyrimidines useful as calcium channel blockers |
| NZ219299A (en) * | 1986-03-14 | 1989-01-06 | Squibb & Sons Inc | Pyrimidine derivatives |
-
1987
- 1987-03-05 IL IL81800A patent/IL81800A0/xx not_active IP Right Cessation
- 1987-03-06 PH PH34991A patent/PH27052A/en unknown
- 1987-03-11 JP JP62057890A patent/JPH0819113B2/ja not_active Expired - Lifetime
- 1987-03-11 IE IE63387A patent/IE60114B1/en not_active IP Right Cessation
- 1987-03-12 FI FI871087A patent/FI96683C/fi not_active IP Right Cessation
- 1987-03-12 ES ES198787302130T patent/ES2039234T3/es not_active Expired - Lifetime
- 1987-03-12 EP EP87302130A patent/EP0237347B1/en not_active Expired - Lifetime
- 1987-03-12 DE DE8787302130T patent/DE3770661D1/de not_active Expired - Fee Related
- 1987-03-13 DK DK131887A patent/DK169031B1/da not_active IP Right Cessation
- 1987-03-13 SU SU874202205A patent/SU1713437A3/ru active
- 1987-03-13 HU HU871127A patent/HU206091B/hu not_active IP Right Cessation
- 1987-03-13 PT PT84479A patent/PT84479B/pt not_active IP Right Cessation
- 1987-03-13 KR KR1019870002239A patent/KR900005014B1/ko not_active IP Right Cessation
- 1987-03-13 NO NO871044A patent/NO871044L/no unknown
- 1987-03-13 PL PL1987264629A patent/PL153727B1/pl unknown
- 1987-03-16 CA CA000532125A patent/CA1337655C/en not_active Expired - Fee Related
-
1991
- 1991-09-12 GR GR91401319T patent/GR3002715T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PL264629A1 (en) | 1988-07-21 |
| KR900005014B1 (ko) | 1990-07-16 |
| PL153727B1 (en) | 1991-05-31 |
| JPS62265271A (ja) | 1987-11-18 |
| PT84479B (pt) | 1990-08-31 |
| IE870633L (en) | 1987-09-14 |
| IE60114B1 (en) | 1994-06-01 |
| EP0237347A3 (en) | 1988-11-02 |
| ES2039234T3 (es) | 1993-09-16 |
| FI96683B (fi) | 1996-04-30 |
| HU206091B (en) | 1992-08-28 |
| PT84479A (en) | 1987-04-01 |
| DK131887A (da) | 1987-09-15 |
| NO871044L (no) | 1987-09-15 |
| KR870008856A (ko) | 1987-10-21 |
| GR3002715T3 (en) | 1993-01-25 |
| HUT43832A (en) | 1987-12-28 |
| EP0237347B1 (en) | 1991-06-12 |
| FI871087A (fi) | 1987-09-15 |
| DE3770661D1 (de) | 1991-07-18 |
| DK131887D0 (da) | 1987-03-13 |
| IL81800A0 (en) | 1987-10-20 |
| FI96683C (fi) | 1996-08-12 |
| DK169031B1 (da) | 1994-08-01 |
| CA1337655C (en) | 1995-11-28 |
| JPH0819113B2 (ja) | 1996-02-28 |
| EP0237347A2 (en) | 1987-09-16 |
| FI871087A0 (fi) | 1987-03-12 |
| SU1713437A3 (ru) | 1992-02-15 |
| NO871044D0 (no) | 1987-03-13 |
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