AU725689B2 - Epoxy-steroidal aldosterone antagonist and angiotensin II antagonist combination therapy for treatment of congestive heart failure - Google Patents

Epoxy-steroidal aldosterone antagonist and angiotensin II antagonist combination therapy for treatment of congestive heart failure Download PDF

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Publication number: AU725689B2
Authority: AU; Australia
Prior art keywords: pub; angiotensin; epoxy; compound; antagonists
Prior art date: 1995-06-07
Legal status (The legal status 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 status listed.): Ceased

Application number

AU61577/96A

Other languages

English (en)

Other versions

AU6157796A (en

Inventor

John C. Alexander

Richard J. Gorczynski

Joseph R. Schuh

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

GD Searle LLC

Original Assignee

GD Searle LLC

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

2000-10-19

1996-06-05 Application filed by GD Searle LLC filed Critical GD Searle LLC

1996-12-30 Publication of AU6157796A publication Critical patent/AU6157796A/en

2000-10-19 Application granted granted Critical

2000-10-19 Publication of AU725689B2 publication Critical patent/AU725689B2/en

2016-06-05 Anticipated expiration legal-status Critical

Status Ceased legal-status Critical Current

Links

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238000002648 combination therapy Methods 0.000 title claims description 28
206010019280 Heart failures Diseases 0.000 title claims description 25
206010007559 Cardiac failure congestive Diseases 0.000 title claims description 20
229940123413 Angiotensin II antagonist Drugs 0.000 title description 131
239000002170 aldosterone antagonist Substances 0.000 title description 5
229940083712 aldosterone antagonist Drugs 0.000 title description 5
102000003979 Mineralocorticoid Receptors Human genes 0.000 claims abstract description 37
108090000375 Mineralocorticoid Receptors Proteins 0.000 claims abstract description 37
229940044551 receptor antagonist Drugs 0.000 claims abstract description 36
239000002464 receptor antagonist Substances 0.000 claims abstract description 36
229940126317 angiotensin II receptor antagonist Drugs 0.000 claims abstract description 21
150000001875 compounds Chemical class 0.000 claims description 205
-1 EMD-66397 Chemical compound 0.000 claims description 68
206010020772 Hypertension Diseases 0.000 claims description 22
239000004593 Epoxy Substances 0.000 claims description 17
150000003839 salts Chemical class 0.000 claims description 16
238000000034 method Methods 0.000 claims description 15
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical class [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 11
208000024172 Cardiovascular disease Diseases 0.000 claims description 10
208000035475 disorder Diseases 0.000 claims description 9
230000003637 steroidlike Effects 0.000 claims description 9
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AGWFKXDTYITCSP-NHGLSFBUSA-N (8s,9s,10r,13r,14s,17r)-17-(2-carboxyethyl)-10,13-dimethyl-2,3,6,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthrene-7-carboxylic acid Chemical compound C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)CCC(O)=O)[C@@H]4[C@@H]3C(C(O)=O)CC2=C1 AGWFKXDTYITCSP-NHGLSFBUSA-N 0.000 claims description 7
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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 4
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 4
239000002083 C09CA01 - Losartan Substances 0.000 claims description 4
239000002080 C09CA02 - Eprosartan Substances 0.000 claims description 4
239000004072 C09CA03 - Valsartan Substances 0.000 claims description 4
239000002947 C09CA04 - Irbesartan Substances 0.000 claims description 4
239000002081 C09CA05 - Tasosartan Substances 0.000 claims description 4
239000002053 C09CA06 - Candesartan Substances 0.000 claims description 4
239000005537 C09CA07 - Telmisartan Substances 0.000 claims description 4
206010016654 Fibrosis Diseases 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
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229960004349 candesartan cilexetil Drugs 0.000 claims description 4
208000019425 cirrhosis of liver Diseases 0.000 claims description 4
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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
229960000519 losartan potassium Drugs 0.000 claims description 4
150000004702 methyl esters Chemical class 0.000 claims description 4
OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 claims description 4
229960001379 saralasin acetate Drugs 0.000 claims description 4
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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 4
229960005187 telmisartan Drugs 0.000 claims description 4
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ACWBQPMHZXGDFX-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=NN1 ACWBQPMHZXGDFX-QFIPXVFZSA-N 0.000 claims description 4
ZBOYJODMIAUJHH-SANMLTNESA-N (2s)-1-[[2,6-dimethoxy-4-[(2-methyl-3-phenylphenyl)methoxy]phenyl]methyl]piperidine-2-carboxylic acid Chemical compound C=1C(OC)=C(CN2[C@@H](CCCC2)C(O)=O)C(OC)=CC=1OCC(C=1C)=CC=CC=1C1=CC=CC=C1 ZBOYJODMIAUJHH-SANMLTNESA-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
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 3
FLOKGHWIQFCIJW-UHFFFAOYSA-N 2-butyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylic acid Chemical compound CCCCC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 FLOKGHWIQFCIJW-UHFFFAOYSA-N 0.000 claims description 3
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206010054936 Cardiac cirrhosis Diseases 0.000 claims description 3
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 3
125000004494 ethyl ester group Chemical group 0.000 claims description 3
ZEUXAIYYDDCIRX-UHFFFAOYSA-N losartan carboxylic acid Chemical compound CCCCC1=NC(Cl)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C2=NNN=N2)C=C1 ZEUXAIYYDDCIRX-UHFFFAOYSA-N 0.000 claims description 3
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 3
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 3
229960004785 saralasin Drugs 0.000 claims description 3
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 2
HHFYOGBTLFTWQX-XWGVYQGASA-N (2s,4s)-4-(4-carboxyphenoxy)-1-[(2s)-2-[4-[(2-sulfobenzoyl)amino]imidazol-1-yl]octanoyl]pyrrolidine-2-carboxylic acid Chemical compound O([C@@H]1CN([C@@H](C1)C(O)=O)C(=O)[C@H](CCCCCC)N1C=C(NC(=O)C=2C(=CC=CC=2)S(O)(=O)=O)N=C1)C1=CC=C(C(O)=O)C=C1 HHFYOGBTLFTWQX-XWGVYQGASA-N 0.000 claims description 2
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 2
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 2
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 2
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
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 2
MGSBGAVGFLLRDU-UHFFFAOYSA-N 2-propyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]-5-[2-(2,2,2-trifluoroacetyl)pyrrol-1-yl]imidazole-4-carboxylic acid Chemical compound CCCC1=NC(N2C(=CC=C2)C(=O)C(F)(F)F)=C(C(O)=O)N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 MGSBGAVGFLLRDU-UHFFFAOYSA-N 0.000 claims description 2
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 2
RQGDXPDTZWGCQI-UHFFFAOYSA-N 5-(1,1,2,2,2-pentafluoroethyl)-2-propyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carboxylic acid Chemical compound CCCC1=NC(C(F)(F)C(F)(F)F)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C2=NNN=N2)C=C1 RQGDXPDTZWGCQI-UHFFFAOYSA-N 0.000 claims description 2
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 2
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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 2
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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 2
108700028065 Sar(1)-Me-Tyr(4)- angiotensin II Proteins 0.000 claims description 2
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 2
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 2
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 2
229950006241 saprisartan Drugs 0.000 claims description 2
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 2
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 2
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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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- 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

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Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical & Material Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Epidemiology (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Cardiology (AREA)
Organic Chemistry (AREA)
Heart & Thoracic Surgery (AREA)
Vascular Medicine (AREA)
Urology & Nephrology (AREA)
Hospice & Palliative Care (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Plural Heterocyclic Compounds (AREA)
Steroid Compounds (AREA)
Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Quinoline Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Pyrrole Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

AU61577/96A 1995-06-07 1996-06-05 Epoxy-steroidal aldosterone antagonist and angiotensin II antagonist combination therapy for treatment of congestive heart failure Ceased AU725689B2 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US48645695A	1995-06-07	1995-06-07
US08/486456		1995-06-07
PCT/US1996/009335 WO1996040257A1 (en)	1995-06-07	1996-06-05	Epoxy-steroidal aldosterone antagonist and angiotensin ii antagonist combination therapy for treatment of congestive heart failure

Related Child Applications (1)

Application Number	Title	Priority Date	Filing Date
AU53494/00A Division AU5349400A (en)	1995-06-07	2000-08-18	Epoxy-steroidal aldosterone antagonist and angiotensin II antagonist combination therapy for the treatment of congestive heart failure

Publications (2)

Publication Number	Publication Date
AU6157796A AU6157796A (en)	1996-12-30
AU725689B2 true AU725689B2 (en)	2000-10-19

Family

ID=23931955

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
AU61577/96A Ceased AU725689B2 (en)	1995-06-07	1996-06-05	Epoxy-steroidal aldosterone antagonist and angiotensin II antagonist combination therapy for treatment of congestive heart failure

Country Status (21)

Country	Link
US (1)	US6653306B1 (2)
EP (1)	EP0831910B1 (2)
JP (1)	JPH11507627A (2)
KR (1)	KR100618466B1 (2)
CN (2)	CN1522701A (2)
AT (1)	ATE209047T1 (2)
AU (1)	AU725689B2 (2)
BR (1)	BR9609066A (2)
CA (1)	CA2224079A1 (2)
CZ (1)	CZ297975B6 (2)
DE (1)	DE69617235T2 (2)
DK (1)	DK0831910T3 (2)
ES (1)	ES2167571T3 (2)
IL (1)	IL122242A (2)
NO (1)	NO318184B1 (2)
NZ (1)	NZ310730A (2)
PL (1)	PL185150B1 (2)
PT (1)	PT831910E (2)
RO (1)	RO118046B1 (2)
RU (1)	RU2166330C2 (2)
WO (1)	WO1996040257A1 (2)

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1996
- 1996-06-05 DK DK96919170T patent/DK0831910T3/da active
- 1996-06-05 AT AT96919170T patent/ATE209047T1/de not_active IP Right Cessation
- 1996-06-05 NZ NZ310730A patent/NZ310730A/xx unknown
- 1996-06-05 RO RO97-02272A patent/RO118046B1/ro unknown
- 1996-06-05 CZ CZ0385097A patent/CZ297975B6/cs not_active IP Right Cessation
- 1996-06-05 AU AU61577/96A patent/AU725689B2/en not_active Ceased
- 1996-06-05 BR BR9609066A patent/BR9609066A/pt not_active Application Discontinuation
- 1996-06-05 CA CA002224079A patent/CA2224079A1/en not_active Abandoned
- 1996-06-05 JP JP9501678A patent/JPH11507627A/ja not_active Ceased
- 1996-06-05 EP EP96919170A patent/EP0831910B1/en not_active Expired - Lifetime
- 1996-06-05 WO PCT/US1996/009335 patent/WO1996040257A1/en not_active Ceased
- 1996-06-05 RU RU98100250/14A patent/RU2166330C2/ru not_active IP Right Cessation
- 1996-06-05 CN CNA2004100027960A patent/CN1522701A/zh active Pending
- 1996-06-05 IL IL12224296A patent/IL122242A/en not_active IP Right Cessation
- 1996-06-05 DE DE69617235T patent/DE69617235T2/de not_active Expired - Fee Related
- 1996-06-05 KR KR1019970709029A patent/KR100618466B1/ko not_active Expired - Fee Related
- 1996-06-05 ES ES96919170T patent/ES2167571T3/es not_active Expired - Lifetime
- 1996-06-05 CN CNB961961554A patent/CN1142793C/zh not_active Expired - Fee Related
- 1996-06-05 PT PT96919170T patent/PT831910E/pt unknown
- 1996-06-05 PL PL96324001A patent/PL185150B1/pl not_active IP Right Cessation
1997
- 1997-01-09 US US08/781,786 patent/US6653306B1/en not_active Expired - Fee Related
2004
- 2004-11-23 NO NO19975741A patent/NO318184B1/no unknown

Also Published As

Publication number	Publication date
BR9609066A (pt)	1999-01-26
DE69617235T2 (de)	2002-07-25
ATE209047T1 (de)	2001-12-15
CN1142793C (zh)	2004-03-24
ES2167571T3 (es)	2002-05-16
US6653306B1 (en)	2003-11-25
CN1522701A (zh)	2004-08-25
IL122242A0 (en)	1998-04-05
DE69617235D1 (de)	2002-01-03
KR100618466B1 (ko)	2006-12-13
PL185150B1 (pl)	2003-03-31
JPH11507627A (ja)	1999-07-06
CA2224079A1 (en)	1996-12-19
NO975741L (no)	1998-01-29
NO318184B1 (no)	2005-02-14
WO1996040257A1 (en)	1996-12-19
EP0831910A1 (en)	1998-04-01
CN1192697A (zh)	1998-09-09
RU2166330C2 (ru)	2001-05-10
NZ310730A (en)	2001-01-26
PT831910E (pt)	2002-05-31
NO975741D0 (no)	1997-12-05
EP0831910B1 (en)	2001-11-21
CZ385097A3 (cs)	1998-06-17
KR19990022548A (ko)	1999-03-25
CZ297975B6 (cs)	2007-05-09
IL122242A (en)	2001-07-24
PL324001A1 (en)	1998-04-27
AU6157796A (en)	1996-12-30
RO118046B1 (ro)	2003-01-30
DK0831910T3 (da)	2002-05-21

Legal Events

Date	Code	Title	Description
2001-02-15	FGA	Letters patent sealed or granted (standard patent)

Publication	Publication Date	Title
AU725689B2 (en)	2000-10-19	Epoxy-steroidal aldosterone antagonist and angiotensin II antagonist combination therapy for treatment of congestive heart failure
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
ZA200201470B (en)	2003-09-23	Use of inhibitors of the renin-angiotensin system in the prevention of cardiovascular events.
RU2384346C2 (ru)	2010-03-20	Фармацевтические композиции, содержащие nep-ингибиторы, ингибиторы эндогенной эндотелинпродуцирующей системы и антагонисты at1-рецептора
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
US20100203132A1 (en)	2010-08-12	Pharmaceutical Compositions Comprising NEP-Inhibitors, Inhibitors of the Endogenous Endothelin Producing System and AT1 Receptor Antagonists
AU4264200A (en)	2000-09-07	Spironolactone and angiotensin II antagonist combination therapy for treatment of congestive heart failure
WO2007053406A1 (en)	2007-05-10	Combinations of antihypertensive and cholesterol lowering agents
HK1096293B (en)	2009-07-31	Pharmaceutical composition comprising a selective i1 imidazoline receptor agonist and an angiotensin ii receptor blocker