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 failure

Info

Publication number: IL122246A
Authority: IL; Israel
Prior art keywords: angiotensin; receptor antagonist; combination; compound; spironolactone
Prior art date: 1995-06-07

Application number

IL12224696A

Other languages

English (en)

Hebrew (he)

Other versions

IL122246A0 (en

Original Assignee

Searle & Co

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1995-06-07

Filing date

1996-06-05

Publication date

2004-06-01

1996-06-05 Application filed by Searle & Co filed Critical Searle & Co

1996-06-05 Priority to IL16087196A priority Critical patent/IL160871A0/xx

1998-04-05 Publication of IL122246A0 publication Critical patent/IL122246A0/xx

2004-06-01 Publication of IL122246A publication Critical patent/IL122246A/en

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
SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 claims 4
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
229960004773 losartan Drugs 0.000 claims 2
KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 claims 2
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
238000002648 combination therapy Methods 0.000 abstract description 26
206010020772 Hypertension Diseases 0.000 abstract description 20
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 7
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 abstract description 6
208000024172 Cardiovascular disease Diseases 0.000 abstract description 4
206010016654 Fibrosis Diseases 0.000 abstract description 4
208000019425 cirrhosis of liver Diseases 0.000 abstract description 4
125000004076 pyridyl group Chemical group 0.000 abstract description 4
206010003445 Ascites Diseases 0.000 abstract description 3
230000007882 cirrhosis Effects 0.000 abstract description 3
208000035475 disorder Diseases 0.000 abstract description 3
125000001425 triazolyl group Chemical group 0.000 abstract description 2
KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 abstract 1
239000005557 antagonist Substances 0.000 description 44
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125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000001422 pyrrolinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
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125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
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239000004332 silver Substances 0.000 description 1
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239000008117 stearic acid Substances 0.000 description 1
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125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
229940124530 sulfonamide Drugs 0.000 description 1
150000003456 sulfonamides Chemical class 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
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208000011580 syndromic disease Diseases 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
239000003451 thiazide diuretic agent Substances 0.000 description 1
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230000001052 transient effect Effects 0.000 description 1
230000032258 transport Effects 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 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)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
Engineering & Computer Science (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Epidemiology (AREA)
Bioinformatics & Cheminformatics (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (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)

IL12224696A 1995-06-07 1996-06-05 Combination of spironolactone and angiotensin II antagonist for the treatment of heart failure IL122246A (en)

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 (2)
EP (1)	EP0831911B1 (2)
JP (1)	JPH11509838A (2)
KR (1)	KR19990022723A (2)
CN (1)	CN1192696A (2)
AT (1)	ATE216261T1 (2)
AU (1)	AU6158096A (2)
BR (1)	BR9608505A (2)
CA (1)	CA2224222A1 (2)
CZ (1)	CZ291268B6 (2)
DE (1)	DE69620756T2 (2)
DK (1)	DK0831911T3 (2)
ES (1)	ES2175098T3 (2)
IL (1)	IL122246A (2)
PT (1)	PT831911E (2)
WO (1)	WO1996040258A2 (2)

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1996
- 1996-06-05 WO PCT/US1996/009342 patent/WO1996040258A2/en not_active Ceased
- 1996-06-05 CZ CZ19973848A patent/CZ291268B6/cs not_active IP Right Cessation
- 1996-06-05 KR KR1019970709165A patent/KR19990022723A/ko not_active Ceased
- 1996-06-05 AT AT96919173T patent/ATE216261T1/de not_active IP Right Cessation
- 1996-06-05 BR BR9608505A patent/BR9608505A/pt not_active Application Discontinuation
- 1996-06-05 JP JP9501683A patent/JPH11509838A/ja not_active Abandoned
- 1996-06-05 ES ES96919173T patent/ES2175098T3/es not_active Expired - Lifetime
- 1996-06-05 CN CN96196086A patent/CN1192696A/zh active Pending
- 1996-06-05 CA CA002224222A patent/CA2224222A1/en not_active Abandoned
- 1996-06-05 EP EP96919173A patent/EP0831911B1/en not_active Expired - Lifetime
- 1996-06-05 DE DE69620756T patent/DE69620756T2/de not_active Expired - Fee Related
- 1996-06-05 IL IL12224696A patent/IL122246A/en not_active IP Right Cessation
- 1996-06-05 AU AU61580/96A patent/AU6158096A/en not_active Abandoned
- 1996-06-05 DK DK96919173T patent/DK0831911T3/da active
- 1996-06-05 PT PT96919173T patent/PT831911E/pt unknown
2002
- 2002-10-15 US US10/271,362 patent/US20040102423A1/en not_active Abandoned

Also Published As

Publication number	Publication date
DE69620756T2 (de)	2002-11-14
KR19990022723A (ko)	1999-03-25
EP0831911B1 (en)	2002-04-17
CN1192696A (zh)	1998-09-09
DK0831911T3 (da)	2002-07-22
BR9608505A (pt)	1999-07-06
WO1996040258A2 (en)	1996-12-19
PT831911E (pt)	2002-09-30
ATE216261T1 (de)	2002-05-15
IL122246A0 (en)	1998-04-05
EP0831911A2 (en)	1998-04-01
CZ384897A3 (cs)	1998-05-13
US20040102423A1 (en)	2004-05-27
WO1996040258A3 (en)	1997-01-23
DE69620756D1 (de)	2002-05-23
CA2224222A1 (en)	1996-12-19
ES2175098T3 (es)	2002-11-16
AU6158096A (en)	1996-12-30
CZ291268B6 (cs)	2003-01-15
JPH11509838A (ja)	1999-08-31

Legal Events

Date	Code	Title	Description
2004-11-10	FF	Patent granted
2007-03-08	MM9K	Patent not in force due to non-payment of renewal fees

Publication	Publication Date	Title
US6653306B1 (en)	2003-11-25	Epoxy-steroidal aldosterone antagonist and angiotensin II antagonist combination therapy
US20040102423A1 (en)	2004-05-27	Spironolactone and angiotensin II antagonist combination therapy for treatment of congestive heart failure
US20040067915A1 (en)	2004-04-08	Method to treat cardiofibrosis with a combination of an angiotensin II antagonist and spironolactone
US20040053903A1 (en)	2004-03-18	Method to treat cardiofibrosis with a combination therapy of an angiotensin II antagonist and an epoxy-steroidal aldosterone antagonist
RU2384346C2 (ru)	2010-03-20	Фармацевтические композиции, содержащие nep-ингибиторы, ингибиторы эндогенной эндотелинпродуцирующей системы и антагонисты at1-рецептора
ZA200201470B (en)	2003-09-23	Use of inhibitors of the renin-angiotensin system in the prevention of cardiovascular events.
ZA200601804B (en)	2007-05-30	Pharmaceutcal composition comprising a selective II imidazoline receptor agonist and an angiotensin II receptor blocker
AU2003202486B2 (en)	2005-06-16	Epoxy-steroidal aldosterone antagonist and angiotensin II antagonist combination therapy for the treatment of congestive heart failure
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