IL122246A - Combination of spironolactone and angiotensin II antagonist for the treatment of heart failure - Google Patents
Combination of spironolactone and angiotensin II antagonist for the treatment of heart failureInfo
- Publication number
- IL122246A IL122246A IL12224696A IL12224696A IL122246A IL 122246 A IL122246 A IL 122246A IL 12224696 A IL12224696 A IL 12224696A IL 12224696 A IL12224696 A IL 12224696A IL 122246 A IL122246 A IL 122246A
- Authority
- IL
- Israel
- Prior art keywords
- angiotensin
- receptor antagonist
- combination
- compound
- spironolactone
- Prior art date
Links
- 239000002333 angiotensin II receptor antagonist Substances 0.000 title claims abstract description 163
- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 title claims abstract description 43
- 229960002256 spironolactone Drugs 0.000 title claims abstract description 39
- 206010019280 Heart failures Diseases 0.000 title abstract description 22
- 206010007559 Cardiac failure congestive Diseases 0.000 title abstract description 17
- 229940123413 Angiotensin II antagonist Drugs 0.000 title description 133
- 150000001875 compounds Chemical class 0.000 claims abstract description 195
- -1 3,5-dibutyl-1H-1,2,4-triazol-1-yl Chemical group 0.000 claims abstract description 83
- 229940126317 angiotensin II receptor antagonist Drugs 0.000 claims abstract description 29
- 102000003979 Mineralocorticoid Receptors Human genes 0.000 claims abstract description 27
- 108090000375 Mineralocorticoid Receptors Proteins 0.000 claims abstract description 27
- 229940044551 receptor antagonist Drugs 0.000 claims abstract description 23
- 239000002464 receptor antagonist Substances 0.000 claims abstract description 23
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 7
- 239000002934 diuretic Substances 0.000 claims description 14
- RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 claims description 14
- 239000002552 dosage form Substances 0.000 claims description 10
- 230000001882 diuretic effect Effects 0.000 claims description 9
- IDAWWPOAHPVPMY-UHFFFAOYSA-N elisartan Chemical compound CCCCC1=NC(Cl)=C(C(=O)OC(C)OC(=O)OCC)N1CC1=CC=C(C=2C(=CC=CC=2)C2=NNN=N2)C=C1 IDAWWPOAHPVPMY-UHFFFAOYSA-N 0.000 claims description 9
- OLJAPHMBAMBVKL-UHFFFAOYSA-N 5-methyl-7-propyl-8-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]-3h-[1,2,4]triazolo[1,5-c]pyrimidin-2-one Chemical compound CCCC=1N=C(C)N2NC(=O)N=C2C=1CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 OLJAPHMBAMBVKL-UHFFFAOYSA-N 0.000 claims description 8
- 108010083387 Saralasin Proteins 0.000 claims description 8
- 239000004072 C09CA03 - Valsartan Substances 0.000 claims description 7
- 239000005537 C09CA07 - Telmisartan Substances 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 229960005187 telmisartan Drugs 0.000 claims description 7
- 229960004699 valsartan Drugs 0.000 claims description 7
- 239000002081 C09CA05 - Tasosartan Substances 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- 239000005478 Saprisartan Substances 0.000 claims description 6
- DUEWVPTZCSAMNB-UHFFFAOYSA-N Saprisartan Chemical compound NC(=O)C=1N(CC=2C=C3C(Br)=C(OC3=CC=2)C=2C(=CC=CC=2)NS(=O)(=O)C(F)(F)F)C(CC)=NC=1C1CC1 DUEWVPTZCSAMNB-UHFFFAOYSA-N 0.000 claims description 6
- 229950006241 saprisartan Drugs 0.000 claims description 6
- 229960000651 tasosartan Drugs 0.000 claims description 6
- ADXGNEYLLLSOAR-UHFFFAOYSA-N tasosartan Chemical compound C12=NC(C)=NC(C)=C2CCC(=O)N1CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 ADXGNEYLLLSOAR-UHFFFAOYSA-N 0.000 claims description 6
- 239000005479 Ripisartan Substances 0.000 claims description 5
- 229950000980 elisartan Drugs 0.000 claims description 5
- 229950004910 ripisartan Drugs 0.000 claims description 5
- ZPFRAPVRYLGYEC-UHFFFAOYSA-N 1-(4-hydroxyphenyl)-3-(2,4,6-trimethoxyphenyl)propan-1-one Chemical compound COC1=CC(OC)=CC(OC)=C1CCC(=O)C1=CC=C(O)C=C1 ZPFRAPVRYLGYEC-UHFFFAOYSA-N 0.000 claims description 4
- LASWNZRBIPFGHP-UHFFFAOYSA-N 2,7-diethyl-5-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]pyrazolo[1,5-b][1,2,4]triazole Chemical compound N12N=C(CC)N=C2C(CC)=CN1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 LASWNZRBIPFGHP-UHFFFAOYSA-N 0.000 claims description 4
- DNVWFUABLSEXTM-UHFFFAOYSA-N 2-[[1-(1-carboxyheptyl)imidazol-4-yl]carbamoyl]-6-hydroxybenzoic acid Chemical compound CCCCCCC(C(O)=O)N1C=NC(NC(=O)C=2C(=C(O)C=CC=2)C(O)=O)=C1 DNVWFUABLSEXTM-UHFFFAOYSA-N 0.000 claims description 4
- ZHWGRXBJGUEATA-UHFFFAOYSA-N 2-[[4-[[2-butyl-6-[methylcarbamoyl(pentyl)amino]benzimidazol-1-yl]methyl]phenyl]carbamoyl]-3,6-dichlorobenzoic acid Chemical compound C12=CC(N(C(=O)NC)CCCCC)=CC=C2N=C(CCCC)N1CC(C=C1)=CC=C1NC(=O)C1=C(Cl)C=CC(Cl)=C1C(O)=O ZHWGRXBJGUEATA-UHFFFAOYSA-N 0.000 claims description 4
- ZGAFRHMPMVKTNA-UHFFFAOYSA-N 2-[[4-butyl-2-methyl-6-oxo-5-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]pyrimidin-1-yl]methyl]benzoic acid Chemical compound O=C1C(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2NN=NN=2)=C(CCCC)N=C(C)N1CC1=CC=CC=C1C(O)=O ZGAFRHMPMVKTNA-UHFFFAOYSA-N 0.000 claims description 4
- AHZXSVWCNDLJER-UHFFFAOYSA-N 4-[butyl-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]amino]pyrimidine-5-carboxylic acid Chemical compound N=1C=NC=C(C(O)=O)C=1N(CCCC)CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 AHZXSVWCNDLJER-UHFFFAOYSA-N 0.000 claims description 4
- UIYUUEDFAMZISF-FTBISJDPSA-N 6-chloro-1,1-dioxo-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide;(2s)-3-methyl-2-[pentanoyl-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]amino]butanoic acid Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O.C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NNN=N1 UIYUUEDFAMZISF-FTBISJDPSA-N 0.000 claims description 4
- 239000002083 C09CA01 - Losartan Substances 0.000 claims description 4
- 239000002080 C09CA02 - Eprosartan Substances 0.000 claims description 4
- 239000002947 C09CA04 - Irbesartan Substances 0.000 claims description 4
- 239000002053 C09CA06 - Candesartan Substances 0.000 claims description 4
- ZUMPSVPHCDJCMD-UHFFFAOYSA-N abitesartan Chemical compound C1CCCC1(C(O)=O)CN(C(=O)CCCC)CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 ZUMPSVPHCDJCMD-UHFFFAOYSA-N 0.000 claims description 4
- YBZYNINTWCLDQA-UHKVWXOHSA-N acetic acid;(2s)-2-[[(2s)-1-[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-5-(diaminomethylideneamino)-2-[[2-(methylamino)acetyl]amino]pentanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]-3-(1h-imidazol-5-yl)prop Chemical compound O.CC(O)=O.C([C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)CNC)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)C1=CC=C(O)C=C1 YBZYNINTWCLDQA-UHKVWXOHSA-N 0.000 claims description 4
- 229960000932 candesartan Drugs 0.000 claims description 4
- GNRPOJRPMDCDDL-UHFFFAOYSA-N chembl1668123 Chemical compound CCCCC1=NC=2CN3C(CC4)CCC4N3C(=O)C=2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 GNRPOJRPMDCDDL-UHFFFAOYSA-N 0.000 claims description 4
- 229960004563 eprosartan Drugs 0.000 claims description 4
- OROAFUQRIXKEMV-LDADJPATSA-N eprosartan Chemical compound C=1C=C(C(O)=O)C=CC=1CN1C(CCCC)=NC=C1\C=C(C(O)=O)/CC1=CC=CS1 OROAFUQRIXKEMV-LDADJPATSA-N 0.000 claims description 4
- 229960002198 irbesartan Drugs 0.000 claims description 4
- YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 claims description 4
- PFGWGEPQIUAZME-NXSMLHPHSA-N saralasin Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)CNC)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)C1=CC=C(O)C=C1 PFGWGEPQIUAZME-NXSMLHPHSA-N 0.000 claims description 4
- 229960004785 saralasin Drugs 0.000 claims description 4
- 229960001379 saralasin acetate Drugs 0.000 claims description 4
- WJXAVNPIJIPGMN-PNGYUKAISA-N (2s)-2-[[(2s)-1-[(2s)-2-[[(2s,3s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-5-(diaminomethylideneamino)-2-[[2-(methylamino)acetyl]amino]pentanoyl]amino]-3-methylbutanoyl]amino]-3-(4-methoxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]py Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)CNC)C(C)C)C1=CC=C(OC)C=C1 WJXAVNPIJIPGMN-PNGYUKAISA-N 0.000 claims description 3
- GGKXIITZBSPCQP-IZIWAXSGSA-N (2s,4s,5s)-5-[[(2s)-2-[[(2s)-2-benzyl-3-tert-butylsulfonylpropanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-n-butyl-6-cyclohexyl-4-hydroxy-2-propan-2-ylhexanamide Chemical compound C([C@@H]([C@@H](O)C[C@H](C(=O)NCCCC)C(C)C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC=1C=CC=CC=1)CS(=O)(=O)C(C)(C)C)C1CCCCC1 GGKXIITZBSPCQP-IZIWAXSGSA-N 0.000 claims description 3
- IZQCLVVNYNAYBS-UHFFFAOYSA-N (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-cyclopropyl-3-[4-[2-(2h-tetrazol-5-yl)phenyl]phenoxy]quinoline-4-carboxylate Chemical compound O1C(=O)OC(COC(=O)C=2C3=CC=CC=C3N=C(C=2OC=2C=CC(=CC=2)C=2C(=CC=CC=2)C2=NNN=N2)C2CC2)=C1C IZQCLVVNYNAYBS-UHFFFAOYSA-N 0.000 claims description 3
- KLVDUSUYBDMJKR-SANMLTNESA-N (6s)-1-[(4-amino-3-methylphenyl)methyl]-5-(2,2-diphenylacetyl)-6,7-dihydro-4h-imidazo[4,5-c]pyridine-6-carboxylic acid Chemical compound C1=C(N)C(C)=CC(CN2C=3C[C@H](N(CC=3N=C2)C(=O)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C(O)=O)=C1 KLVDUSUYBDMJKR-SANMLTNESA-N 0.000 claims description 3
- UKEZYWUWLICNPR-UHFFFAOYSA-N 2,6-dibutyl-5-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]-1h-pyrimidin-4-one Chemical compound N1C(CCCC)=NC(=O)C(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C2=NNN=N2)=C1CCCC UKEZYWUWLICNPR-UHFFFAOYSA-N 0.000 claims description 3
- DLMNZGAILMQDHA-UHFFFAOYSA-N 2-[propyl-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]amino]pyridine-3-carboxylic acid Chemical compound N=1C=CC=C(C(O)=O)C=1N(CCC)CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 DLMNZGAILMQDHA-UHFFFAOYSA-N 0.000 claims description 3
- YILJWHUIUCRKEU-UHFFFAOYSA-N 2-butyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]imidazo[4,5-b]pyridine Chemical compound CCCCC1=NC2=CC=CN=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 YILJWHUIUCRKEU-UHFFFAOYSA-N 0.000 claims description 3
- AIGVXGCHRIOQNR-UHFFFAOYSA-N 2-butyl-5-chloro-3-[[1-[2-(2h-tetrazol-5-yl)phenyl]indol-4-yl]methyl]imidazole-4-carboxylic acid Chemical compound CCCCC1=NC(Cl)=C(C(O)=O)N1CC1=CC=CC2=C1C=CN2C1=CC=CC=C1C1=NNN=N1 AIGVXGCHRIOQNR-UHFFFAOYSA-N 0.000 claims description 3
- DYYWUYUUDYPWON-UHFFFAOYSA-N 2-ethyl-5,7-dimethyl-3-[[9-(2h-tetrazol-5-ylmethyl)-9h-fluoren-2-yl]methyl]imidazo[4,5-b]pyridine Chemical compound CCC1=NC2=C(C)C=C(C)N=C2N1CC(C=1)=CC=C(C2=CC=CC=C22)C=1C2CC=1N=NNN=1 DYYWUYUUDYPWON-UHFFFAOYSA-N 0.000 claims description 3
- NAGGAAHTUXEGFG-UHFFFAOYSA-N 5,7-diethyl-1-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]-3,4-dihydro-1,6-naphthyridin-2-one;hydrochloride Chemical compound Cl.O=C1CCC=2C(CC)=NC(CC)=CC=2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 NAGGAAHTUXEGFG-UHFFFAOYSA-N 0.000 claims description 3
- LDILUHSYQQLZRC-UHFFFAOYSA-N 5-[[[4-[2-hydroxy-3-(propan-2-ylamino)propoxy]-1h-indole-2-carbonyl]amino]methyl]-2-propyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carboxylic acid Chemical compound CCCC1=NC(CNC(=O)C=2NC3=CC=CC(OCC(O)CNC(C)C)=C3C=2)=C(C(O)=O)N1CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 LDILUHSYQQLZRC-UHFFFAOYSA-N 0.000 claims description 3
- 108010076395 CGP 38560 Proteins 0.000 claims description 3
- LINHZVMHXABQLB-ZDUSSCGKSA-N Isoboldine Chemical compound CN1CCC2=CC(OC)=C(O)C3=C2[C@@H]1CC1=C3C=C(OC)C(O)=C1 LINHZVMHXABQLB-ZDUSSCGKSA-N 0.000 claims description 3
- 108700028065 Sar(1)-Me-Tyr(4)- angiotensin II Proteins 0.000 claims description 3
- CCYTUJPXAFHZHC-UHFFFAOYSA-L disodium;4-[[2-butyl-5-(carboxylatomethyl)-4-chloroimidazol-1-yl]methyl]benzoate Chemical compound [Na+].[Na+].CCCCC1=NC(Cl)=C(CC([O-])=O)N1CC1=CC=C(C([O-])=O)C=C1 CCYTUJPXAFHZHC-UHFFFAOYSA-L 0.000 claims description 3
- JBEUFWOCGLXNCS-XSFVSMFZSA-N ethyl (2e)-2-[4-ethyl-4-methyl-6-oxo-1-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]piperidin-2-ylidene]acetate Chemical compound CCOC(=O)\C=C1/CC(C)(CC)CC(=O)N1CC1=CC=C(C=2C(=CC=CC=2)C2=NNN=N2)C=C1 JBEUFWOCGLXNCS-XSFVSMFZSA-N 0.000 claims description 3
- AWIVWBRKOUQKEI-UHFFFAOYSA-N methyl 3-[[4-[2-(butoxycarbonylsulfamoyl)phenyl]-2-chlorophenyl]methyl]-5-ethyl-2-propylimidazole-4-carboxylate Chemical compound CCCCOC(=O)NS(=O)(=O)C1=CC=CC=C1C(C=C1Cl)=CC=C1CN1C(C(=O)OC)=C(CC)N=C1CCC AWIVWBRKOUQKEI-UHFFFAOYSA-N 0.000 claims description 3
- ADJDSKWTIYUCDV-UHFFFAOYSA-M potassium;2-butyl-5-methylsulfanyl-3-[[4-[2-(propylcarbamoylsulfamoyl)phenyl]phenyl]methyl]imidazole-4-carboxylate Chemical compound [K+].CCCCC1=NC(SC)=C(C([O-])=O)N1CC1=CC=C(C=2C(=CC=CC=2)S(=O)(=O)NC(=O)NCCC)C=C1 ADJDSKWTIYUCDV-UHFFFAOYSA-M 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- OSDQJFVHDVAJSD-UHFFFAOYSA-M sodium;2-[2-butyl-3-[[4-[(2-carboxybenzoyl)amino]phenyl]methyl]-5-chloroimidazol-4-yl]propanoate Chemical compound [Na+].CCCCC1=NC(Cl)=C(C(C)C([O-])=O)N1CC(C=C1)=CC=C1NC(=O)C1=CC=CC=C1C(O)=O OSDQJFVHDVAJSD-UHFFFAOYSA-M 0.000 claims description 3
- FIKYECRHLXONOX-UHFFFAOYSA-N zolasartan Chemical compound CCCCC1=NC(Cl)=C(C(O)=O)N1CC1=CC=C(OC(=C2Br)C=3C(=CC=CC=3)C3=NNN=N3)C2=C1 FIKYECRHLXONOX-UHFFFAOYSA-N 0.000 claims description 3
- 229950004433 zolasartan Drugs 0.000 claims description 3
- LQRYGEQNLPCYDT-FPYGCLRLSA-N 2-[4-[[2-[(e)-but-1-enyl]-4-chloro-5-(hydroxymethyl)imidazol-1-yl]methyl]phenyl]benzoic acid Chemical compound CC\C=C\C1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C(O)=O)C=C1 LQRYGEQNLPCYDT-FPYGCLRLSA-N 0.000 claims description 2
- UUPNFNCKGJOLQE-UHFFFAOYSA-N 2-[4-[[2-butyl-4-chloro-5-(hydroxymethyl)imidazol-1-yl]methyl]phenyl]benzoic acid Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C(O)=O)C=C1 UUPNFNCKGJOLQE-UHFFFAOYSA-N 0.000 claims description 2
- OFYWYKMCRWMPPQ-UHFFFAOYSA-N 5-ethyl-2-propyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carboxylic acid Chemical compound CCCC1=NC(CC)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C2=NNN=N2)C=C1 OFYWYKMCRWMPPQ-UHFFFAOYSA-N 0.000 claims description 2
- 108010078036 KRI 1177 Proteins 0.000 claims description 2
- UQUFRFSCUYVXBM-UHFFFAOYSA-N methyl 2-hydroxy-3-[[3-(1h-imidazol-5-yl)-2-[[2-(naphthalen-1-ylmethyl)-4-oxo-4-(2-phenylethylamino)butanoyl]amino]propanoyl]amino]-5-methylhexanoate Chemical compound C=1C=CC=CC=1CCNC(=O)CC(CC=1C2=CC=CC=C2C=CC=1)C(=O)NC(C(=O)NC(CC(C)C)C(O)C(=O)OC)CC1=CN=CN1 UQUFRFSCUYVXBM-UHFFFAOYSA-N 0.000 claims description 2
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- SGZAIDDFHDDFJU-UHFFFAOYSA-N candesartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SGZAIDDFHDDFJU-UHFFFAOYSA-N 0.000 claims 2
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- YONOBYIBNBCDSJ-UHFFFAOYSA-N forasartan Chemical group N1=C(CCCC)N=C(CCCC)N1CC1=CC=C(C=2C(=CC=CC=2)C2=NNN=N2)N=C1 YONOBYIBNBCDSJ-UHFFFAOYSA-N 0.000 claims 1
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- 125000003884 phenylalkyl group Chemical group 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
- A61K31/585—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin containing lactone rings, e.g. oxandrolone, bufalin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Steroid Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Peptides Or Proteins (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IL16087196A IL160871A0 (en) | 1995-06-07 | 1996-06-05 | A combination of spirolactone and angiostensin ii receptor agonist |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US48608995A | 1995-06-07 | 1995-06-07 | |
| PCT/US1996/009342 WO1996040258A2 (en) | 1995-06-07 | 1996-06-05 | Spironolactone and angiotensin ii antagonist combination therapy for treatment of congestive heart failure |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL122246A0 IL122246A0 (en) | 1998-04-05 |
| IL122246A true IL122246A (en) | 2004-06-01 |
Family
ID=23930539
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL12224696A IL122246A (en) | 1995-06-07 | 1996-06-05 | Combination of spironolactone and angiotensin II antagonist for the treatment of heart failure |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US20040102423A1 (https=) |
| EP (1) | EP0831911B1 (https=) |
| JP (1) | JPH11509838A (https=) |
| KR (1) | KR19990022723A (https=) |
| CN (1) | CN1192696A (https=) |
| AT (1) | ATE216261T1 (https=) |
| AU (1) | AU6158096A (https=) |
| BR (1) | BR9608505A (https=) |
| CA (1) | CA2224222A1 (https=) |
| CZ (1) | CZ291268B6 (https=) |
| DE (1) | DE69620756T2 (https=) |
| DK (1) | DK0831911T3 (https=) |
| ES (1) | ES2175098T3 (https=) |
| IL (1) | IL122246A (https=) |
| PT (1) | PT831911E (https=) |
| WO (1) | WO1996040258A2 (https=) |
Families Citing this family (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6306826B1 (en) | 1997-06-04 | 2001-10-23 | The Regents Of The University Of California | Treatment of heart failure with growth hormone |
| US6211217B1 (en) | 1999-03-16 | 2001-04-03 | Novartis Ag | Method for reducing pericardial fibrosis and adhesion formation |
| DK1216038T3 (da) | 1999-08-30 | 2005-12-27 | Sanofi Aventis Deutschland | Anvendelse af inhibitorer af reninangiotensinsystemet ved forebyggelsen af cardiovaskulære hændelser |
| WO2001060362A1 (fr) * | 2000-02-18 | 2001-08-23 | Takeda Chemical Industries, Ltd. | INHIBITEURS DE TNF-$g(a) |
| US7482366B2 (en) | 2001-12-21 | 2009-01-27 | X-Ceptor Therapeutics, Inc. | Modulators of LXR |
| EP1465869B1 (en) | 2001-12-21 | 2013-05-15 | Exelixis Patent Company LLC | Modulators of lxr |
| DE10335027A1 (de) * | 2003-07-31 | 2005-02-17 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verwendung von Angiotensin II Rezeptor Antagonisten |
| WO2005089380A2 (en) | 2004-03-16 | 2005-09-29 | The Regents Of The University Of California | Reducing nephropathy with inhibitors of soluble epoxide hydrolase and epoxyeicosanoids |
| US20050026844A1 (en) | 2003-04-03 | 2005-02-03 | Regents Of The University Of California | Inhibitors for the soluble epoxide hydrolase |
| JP2008517072A (ja) * | 2004-10-20 | 2008-05-22 | ザ レジェンツ オブ ザ ユニバーシティー オブ カリフォルニア | 可溶性エポキシド加水分解酵素の改良された阻害剤 |
| EP1831225A2 (en) * | 2004-11-19 | 2007-09-12 | The Regents of the University of California | Anti-inflammatory pyrazolopyrimidines |
| WO2007114926A2 (en) | 2006-04-04 | 2007-10-11 | The Regents Of The University Of California | Kinase antagonists |
| EP2051696A2 (en) * | 2006-08-18 | 2009-04-29 | Morton Grove Pharmaceuticals, Inc. | Stable liquid levetiracetam compositions and methods |
| GB2467670B (en) * | 2007-10-04 | 2012-08-01 | Intellikine Inc | Chemical entities and therapeutic uses thereof |
| MX2010007419A (es) * | 2008-01-04 | 2010-11-12 | Intellikine Inc | Ciertas entidades quimicas, composiciones y metodos. |
| US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
| US8993580B2 (en) | 2008-03-14 | 2015-03-31 | Intellikine Llc | Benzothiazole kinase inhibitors and methods of use |
| EP2252293B1 (en) * | 2008-03-14 | 2018-06-27 | Intellikine, LLC | Kinase inhibitors and methods of use |
| US20110224223A1 (en) * | 2008-07-08 | 2011-09-15 | The Regents Of The University Of California, A California Corporation | MTOR Modulators and Uses Thereof |
| BRPI0915231A2 (pt) * | 2008-07-08 | 2018-06-12 | Intellikine Inc | compostos inibidores de quinase e métodos de uso |
| CA2738429C (en) | 2008-09-26 | 2016-10-25 | Intellikine, Inc. | Heterocyclic kinase inhibitors |
| EP2358720B1 (en) | 2008-10-16 | 2016-03-02 | The Regents of The University of California | Fused ring heteroaryl kinase inhibitors |
| US8476431B2 (en) | 2008-11-03 | 2013-07-02 | Itellikine LLC | Benzoxazole kinase inhibitors and methods of use |
| CN102369205B (zh) | 2009-01-30 | 2014-10-29 | 武田药品工业株式会社 | 稠环化合物和其用途 |
| JP5789252B2 (ja) | 2009-05-07 | 2015-10-07 | インテリカイン， エルエルシー | 複素環式化合物およびその使用 |
| WO2011047384A2 (en) | 2009-10-16 | 2011-04-21 | The Regents Of The University Of California | Methods of inhibiting ire1 |
| CA2799579A1 (en) | 2010-05-21 | 2011-11-24 | Intellikine, Inc. | Chemical compounds, compositions and methods for kinase modulation |
| JP2013545749A (ja) | 2010-11-10 | 2013-12-26 | インフィニティー ファーマシューティカルズ， インコーポレイテッド | 複素環化合物及びその使用 |
| ES2637113T3 (es) | 2011-01-10 | 2017-10-10 | Infinity Pharmaceuticals, Inc. | Procedimientos para preparar isoquinolinonas y formas sólidas de isoquinolinonas |
| CN107899012A (zh) | 2011-01-11 | 2018-04-13 | 戴麦里克斯生物科学有限公司 | 联合疗法 |
| US9295673B2 (en) | 2011-02-23 | 2016-03-29 | Intellikine Llc | Combination of mTOR inhibitors and P13-kinase inhibitors, and uses thereof |
| CN102816126A (zh) * | 2011-06-07 | 2012-12-12 | 中国药科大学 | 具有心血管活性的胺磺酰芳基取代的三氮唑类衍生物、其制备方法及用途 |
| AR088218A1 (es) | 2011-07-19 | 2014-05-21 | Infinity Pharmaceuticals Inc | Compuestos heterociclicos utiles como inhibidores de pi3k |
| HK1198443A1 (en) | 2011-07-19 | 2015-04-24 | 无限药品股份有限公司 | Heterocyclic compounds and uses thereof |
| MX2014002542A (es) | 2011-08-29 | 2014-07-09 | Infinity Pharmaceuticals Inc | Compuestos heterociclicos y usos de los mismos. |
| CA2846496C (en) | 2011-09-02 | 2020-07-14 | The Regents Of The University Of California | Substituted pyrazolo[3,4-d]pyrimidines and uses thereof |
| US8940742B2 (en) | 2012-04-10 | 2015-01-27 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| US8828998B2 (en) | 2012-06-25 | 2014-09-09 | Infinity Pharmaceuticals, Inc. | Treatment of lupus, fibrotic conditions, and inflammatory myopathies and other disorders using PI3 kinase inhibitors |
| JP2015532287A (ja) | 2012-09-26 | 2015-11-09 | ザ・リージエンツ・オブ・ザ・ユニバーシテイー・オブ・カリフオルニア | Ｉｒｅ１の調節 |
| AU2013337717B2 (en) | 2012-11-01 | 2018-10-25 | Infinity Pharmaceuticals, Inc. | Treatment of cancers using PI3 kinase isoform modulators |
| US9481667B2 (en) | 2013-03-15 | 2016-11-01 | Infinity Pharmaceuticals, Inc. | Salts and solid forms of isoquinolinones and composition comprising and methods of using the same |
| US9751888B2 (en) | 2013-10-04 | 2017-09-05 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| PT3052485T (pt) | 2013-10-04 | 2021-10-22 | Infinity Pharmaceuticals Inc | Compostos heterocíclicos e suas utilizações |
| MX382033B (es) | 2014-03-19 | 2025-03-13 | Infinity Pharmaceuticals Inc | Compuestos heterocíclicos para utilizarlos en el tratamiento de trastornos mediados por pi3k-gamma. |
| WO2015160975A2 (en) | 2014-04-16 | 2015-10-22 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| WO2016054491A1 (en) | 2014-10-03 | 2016-04-07 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| WO2016141182A1 (en) | 2015-03-03 | 2016-09-09 | Yee Richard W | Compositions and methods for treating ocular diseases |
| WO2017048702A1 (en) | 2015-09-14 | 2017-03-23 | Infinity Pharmaceuticals, Inc. | Solid forms of isoquinolinone derivatives, process of making, compositions comprising, and methods of using the same |
| WO2017161116A1 (en) | 2016-03-17 | 2017-09-21 | Infinity Pharmaceuticals, Inc. | Isotopologues of isoquinolinone and quinazolinone compounds and uses thereof as pi3k kinase inhibitors |
| WO2017214269A1 (en) | 2016-06-08 | 2017-12-14 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| SG11201811237WA (en) | 2016-06-24 | 2019-01-30 | Infinity Pharmaceuticals Inc | Combination therapies |
| ES2984389T3 (es) | 2016-06-29 | 2024-10-29 | Univ Montreal | Heterociclos de biarilmetilo |
| CA3121202A1 (en) | 2018-11-30 | 2020-06-04 | Nuvation Bio Inc. | Pyrrole and pyrazole compounds and methods of use thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3257390A (en) * | 1963-06-12 | 1966-06-21 | Merck & Co Inc | Ring a unsaturated 21-hydroxy-3-oxo-17alpha-pregnane-17-carboxylic acid lactone diuretic agents |
| DE2652761C2 (de) * | 1976-11-16 | 1985-11-21 | Schering AG, 1000 Berlin und 4709 Bergkamen | 15,16-Methylen-Spirolactone, Verfahren zu deren Herstellung und diese enthaltende Arzneimittel |
| DE3506100A1 (de) * | 1985-02-18 | 1986-08-21 | Schering AG, 1000 Berlin und 4709 Bergkamen | 1(alpha).7(alpha)-dithiosubstituierte spirolactone, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
| JPH05504969A (ja) * | 1990-02-13 | 1993-07-29 | メルク・エンド・カムパニー・インコーポレーテツド | 置換ベンジル要素を含有するアンギオテンシン２アンタゴニスト類 |
| WO1991015206A1 (en) * | 1990-04-05 | 1991-10-17 | E.I. Du Pont De Nemours And Company | Treatment of glaucoma and ocular hypertension with imidazole angiotensin-ii receptor antagonists |
| CA2053148A1 (en) * | 1990-10-16 | 1992-04-17 | Karnail Atwal | Dihydropyrimidine derivatives |
| US5049565A (en) * | 1990-12-07 | 1991-09-17 | Merck & Co., Inc. | Microbial transformation process for preparing anti-hypertensive products |
| CA2109524A1 (en) * | 1991-05-10 | 1992-11-11 | Prasun K. Chakravarty | Acidic aralkyl triazole derivatives active as angiotensin ii antagonists |
| US5529992A (en) * | 1992-04-21 | 1996-06-25 | Curators Of The University Of Missouri | Method for inhibiting myocardial fibrosis by administering an aldosterone antagonist which suppresses aldoster one receptors |
| US5264447A (en) * | 1992-09-01 | 1993-11-23 | Merck & Co., Inc. | Angiotensin II antagonist |
| AU5449194A (en) * | 1992-10-26 | 1994-05-24 | Merck & Co., Inc. | Combinations of angiotensin-ii receptor antagonists and diuretics |
| CA2125251C (en) * | 1993-06-07 | 2005-04-26 | Yoshiyuki Inada | A pharmaceutical composition for angiotensin ii-mediated diseases |
-
1996
- 1996-06-05 KR KR1019970709165A patent/KR19990022723A/ko not_active Ceased
- 1996-06-05 EP EP96919173A patent/EP0831911B1/en not_active Expired - Lifetime
- 1996-06-05 CN CN96196086A patent/CN1192696A/zh active Pending
- 1996-06-05 IL IL12224696A patent/IL122246A/en not_active IP Right Cessation
- 1996-06-05 DE DE69620756T patent/DE69620756T2/de not_active Expired - Fee Related
- 1996-06-05 AT AT96919173T patent/ATE216261T1/de not_active IP Right Cessation
- 1996-06-05 JP JP9501683A patent/JPH11509838A/ja not_active Abandoned
- 1996-06-05 WO PCT/US1996/009342 patent/WO1996040258A2/en not_active Ceased
- 1996-06-05 PT PT96919173T patent/PT831911E/pt unknown
- 1996-06-05 ES ES96919173T patent/ES2175098T3/es not_active Expired - Lifetime
- 1996-06-05 CA CA002224222A patent/CA2224222A1/en not_active Abandoned
- 1996-06-05 BR BR9608505A patent/BR9608505A/pt not_active Application Discontinuation
- 1996-06-05 AU AU61580/96A patent/AU6158096A/en not_active Abandoned
- 1996-06-05 DK DK96919173T patent/DK0831911T3/da active
- 1996-06-05 CZ CZ19973848A patent/CZ291268B6/cs not_active IP Right Cessation
-
2002
- 2002-10-15 US US10/271,362 patent/US20040102423A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| KR19990022723A (ko) | 1999-03-25 |
| CZ291268B6 (cs) | 2003-01-15 |
| AU6158096A (en) | 1996-12-30 |
| ES2175098T3 (es) | 2002-11-16 |
| US20040102423A1 (en) | 2004-05-27 |
| WO1996040258A3 (en) | 1997-01-23 |
| EP0831911B1 (en) | 2002-04-17 |
| CA2224222A1 (en) | 1996-12-19 |
| JPH11509838A (ja) | 1999-08-31 |
| DK0831911T3 (da) | 2002-07-22 |
| IL122246A0 (en) | 1998-04-05 |
| DE69620756T2 (de) | 2002-11-14 |
| CZ384897A3 (cs) | 1998-05-13 |
| PT831911E (pt) | 2002-09-30 |
| BR9608505A (pt) | 1999-07-06 |
| WO1996040258A2 (en) | 1996-12-19 |
| EP0831911A2 (en) | 1998-04-01 |
| CN1192696A (zh) | 1998-09-09 |
| DE69620756D1 (de) | 2002-05-23 |
| ATE216261T1 (de) | 2002-05-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| MM9K | Patent not in force due to non-payment of renewal fees |