DE69617235T2 - Epoxysteroide aldosteronantagonist und angiotensin ii rezeptor antagonist kombinationstherapie zur behandlung von congestivem herzversagen - Google Patents
Epoxysteroide aldosteronantagonist und angiotensin ii rezeptor antagonist kombinationstherapie zur behandlung von congestivem herzversagenInfo
- Publication number
- DE69617235T2 DE69617235T2 DE69617235T DE69617235T DE69617235T2 DE 69617235 T2 DE69617235 T2 DE 69617235T2 DE 69617235 T DE69617235 T DE 69617235T DE 69617235 T DE69617235 T DE 69617235T DE 69617235 T2 DE69617235 T2 DE 69617235T2
- Authority
- DE
- Germany
- Prior art keywords
- angiotensin
- epoxy
- receptor antagonist
- combination
- oxo
- Prior art date
- 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.)
- Expired - Fee Related
Links
- 239000002333 angiotensin II receptor antagonist Substances 0.000 title claims abstract description 173
- 229940126317 angiotensin II receptor antagonist Drugs 0.000 title claims abstract description 18
- 238000002648 combination therapy Methods 0.000 title description 26
- 206010019280 Heart failures Diseases 0.000 title description 23
- 206010007559 Cardiac failure congestive Diseases 0.000 title description 17
- 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 24
- 239000002464 receptor antagonist Substances 0.000 claims abstract description 24
- -1 3,5-dibutyl-1H- 1,2,4-triazol-1-yl Chemical group 0.000 claims description 61
- 150000001875 compounds Chemical class 0.000 claims description 56
- 150000003839 salts Chemical class 0.000 claims description 15
- 239000004593 Epoxy Substances 0.000 claims description 12
- 230000003637 steroidlike Effects 0.000 claims description 8
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical class [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 4
- 108010083387 Saralasin Proteins 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 2
- 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 2
- 229960004785 saralasin Drugs 0.000 claims description 2
- 125000000457 gamma-lactone group Chemical group 0.000 claims 6
- GHOSNRCGJFBJIB-UHFFFAOYSA-N Candesartan cilexetil Chemical compound C=12N(CC=3C=CC(=CC=3)C=3C(=CC=CC=3)C3=NNN=N3)C(OCC)=NC2=CC=CC=1C(=O)OC(C)OC(=O)OC1CCCCC1 GHOSNRCGJFBJIB-UHFFFAOYSA-N 0.000 claims 4
- 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 4
- 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 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 2
- 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 2
- 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 2
- 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 2
- 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 2
- 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 2
- 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 2
- 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 2
- 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 2
- 239000002083 C09CA01 - Losartan Substances 0.000 claims 2
- 239000002080 C09CA02 - Eprosartan Substances 0.000 claims 2
- 239000004072 C09CA03 - Valsartan Substances 0.000 claims 2
- 239000002947 C09CA04 - Irbesartan Substances 0.000 claims 2
- 239000002081 C09CA05 - Tasosartan Substances 0.000 claims 2
- 239000002053 C09CA06 - Candesartan Substances 0.000 claims 2
- 239000005537 C09CA07 - Telmisartan Substances 0.000 claims 2
- 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 2
- 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 2
- 229960000932 candesartan Drugs 0.000 claims 2
- 229960004349 candesartan cilexetil Drugs 0.000 claims 2
- 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 2
- 229960004563 eprosartan Drugs 0.000 claims 2
- 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 2
- 229960002198 irbesartan Drugs 0.000 claims 2
- 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 2
- 229960000519 losartan potassium Drugs 0.000 claims 2
- 150000004702 methyl esters Chemical class 0.000 claims 2
- 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 2
- 229960001379 saralasin acetate Drugs 0.000 claims 2
- 229960000651 tasosartan Drugs 0.000 claims 2
- 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 2
- 229960005187 telmisartan Drugs 0.000 claims 2
- 229960004699 valsartan Drugs 0.000 claims 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 2
- 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 1
- 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 1
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- 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 1
- 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 1
- OLQFKFSAJNUOPT-UHFFFAOYSA-N 2-[4-[[2-butyl-6-(cyclohexylcarbamoylamino)benzimidazol-1-yl]methyl]phenyl]benzoic acid Chemical compound C1=C2N(CC=3C=CC(=CC=3)C=3C(=CC=CC=3)C(O)=O)C(CCCC)=NC2=CC=C1NC(=O)NC1CCCCC1 OLQFKFSAJNUOPT-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 108010076395 CGP 38560 Proteins 0.000 claims 1
- 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 1
- 108010078036 KRI 1177 Proteins 0.000 claims 1
- 239000005478 Saprisartan Substances 0.000 claims 1
- 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 1
- 108700028065 Sar(1)-Me-Tyr(4)- angiotensin II Proteins 0.000 claims 1
- 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 1
- 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 1
- 125000004494 ethyl ester group Chemical group 0.000 claims 1
- 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 1
- 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 1
- 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 1
- 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 1
- 229950006241 saprisartan Drugs 0.000 claims 1
- 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 1
- 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 1
- 229950004433 zolasartan Drugs 0.000 claims 1
- 238000011282 treatment Methods 0.000 abstract description 10
- 229940123413 Angiotensin II antagonist Drugs 0.000 description 155
- 239000005557 antagonist Substances 0.000 description 36
- PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 0.000 description 28
- 229960002478 aldosterone Drugs 0.000 description 28
- PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 description 27
- 125000004432 carbon atom Chemical group C* 0.000 description 21
- 230000002378 acidificating effect Effects 0.000 description 20
- 206010020772 Hypertension Diseases 0.000 description 19
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II 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](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 19
- 229950006323 angiotensin ii Drugs 0.000 description 19
- 235000002639 sodium chloride Nutrition 0.000 description 19
- 102000005862 Angiotensin II Human genes 0.000 description 18
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Classifications
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- 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
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- 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
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (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)
- Pyrrole Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Quinoline Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US48645695A | 1995-06-07 | 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 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69617235D1 DE69617235D1 (de) | 2002-01-03 |
| DE69617235T2 true DE69617235T2 (de) | 2002-07-25 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69617235T Expired - Fee Related DE69617235T2 (de) | 1995-06-07 | 1996-06-05 | Epoxysteroide aldosteronantagonist und angiotensin ii rezeptor antagonist kombinationstherapie zur behandlung von congestivem herzversagen |
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| CA2277018C (en) * | 1997-01-10 | 2006-10-03 | Merck & Co., Inc. | Use of angiotensin ii antagonists to treat symptomatic heart failure |
| US6201002B1 (en) | 1997-01-10 | 2001-03-13 | Merck & Co., Inc. | Method for reducing mortality with an angiotensin II antagonist |
| US6306826B1 (en) | 1997-06-04 | 2001-10-23 | The Regents Of The University Of California | Treatment of heart failure with growth hormone |
| HK1042252B (en) * | 1999-03-05 | 2004-04-23 | G.D. Searle Llc | Combination therapy of angiotensin converting enzyme inhibitor and epoxy-steroidal aldosterone antagonist for treatment of cardiovascular disease |
| US6211217B1 (en) | 1999-03-16 | 2001-04-03 | Novartis Ag | Method for reducing pericardial fibrosis and adhesion formation |
| US20030083342A1 (en) * | 2002-08-27 | 2003-05-01 | Steele Ronald Edward | Combination of organic compounds |
| JP2004501099A (ja) * | 2000-05-11 | 2004-01-15 | フアルマシア コーポレイション | アルドステロン頂点位相時の放出のためのアルドステロンアンタゴニスト組成物 |
| WO2001097805A2 (en) * | 2000-06-22 | 2001-12-27 | Novartis Ag | Solid valsartan pharmaceutical compositions |
| DE60127410T2 (de) * | 2000-07-27 | 2007-12-13 | Pharmacia Corp. | Kombinationstherapie mit epoxy-steroidalen aldosteronantagonisten und kalziumkanalblocker zur behandlung von kongestivem herzversagen |
| ES2269442T3 (es) * | 2000-07-27 | 2007-04-01 | Pharmacia Corporation | Terapia de combinacion de antagonista de aldosterona e inhibidor de ciclooxigenasa-2 para prevenir o tratar trastornos cardiovasculares relacionados con la inflamacion. |
| JP5082033B2 (ja) | 2001-12-21 | 2012-11-28 | エグゼリクシス パテント カンパニー エルエルシー | Ｌｘｒのモジュレーター |
| US7482366B2 (en) | 2001-12-21 | 2009-01-27 | X-Ceptor Therapeutics, Inc. | Modulators of LXR |
| AU2003233946A1 (en) * | 2002-03-15 | 2003-09-29 | Novartis Ag | 4-(4-methylpiperazin-1-ylmethyl)-n-(4-methyl-3(4-pyridin-3-yl)pyrimidin-2-yl-amino)phenyl)-benzamide for treating ang ii-mediated diseases |
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| CL2004000545A1 (es) * | 2003-03-18 | 2005-01-28 | Pharmacia Corp Sa Organizada B | Uso de un antagonista de los receptores de aldosterona y un antagonista de receptores de endotelina para el tratamiento o profilaxis de una condicion patologica relacionada con hipertension, disfuncion renal, insulinopatia y enfermedades cardiovascul |
| US20050153885A1 (en) * | 2003-10-08 | 2005-07-14 | Yun Anthony J. | Treatment of conditions through modulation of the autonomic nervous system |
| US20070123498A1 (en) * | 2003-10-17 | 2007-05-31 | Shetty Suraj S | Combination of organic compounds |
| US8226977B2 (en) | 2004-06-04 | 2012-07-24 | Teva Pharmaceutical Industries Ltd. | Pharmaceutical composition containing irbesartan |
| US8569277B2 (en) | 2004-08-11 | 2013-10-29 | Palo Alto Investors | Methods of treating a subject for a condition |
| WO2006068760A2 (en) | 2004-11-19 | 2006-06-29 | The Regents Of The University Of California | Anti-inflammatory pyrazolopyrimidines |
| CN101024643A (zh) * | 2006-02-20 | 2007-08-29 | 上海艾力斯医药科技有限公司 | 咪唑－5－羧酸类衍生物、制备方法及其应用 |
| US20080032960A1 (en) | 2006-04-04 | 2008-02-07 | Regents Of The University Of California | PI3 kinase antagonists |
| US20110160232A1 (en) | 2007-10-04 | 2011-06-30 | Pingda Ren | Certain chemical entities and therapeutic uses thereof |
| US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
| MX2010007418A (es) * | 2008-01-04 | 2010-11-12 | Intellikine Inc | Ciertas entidades quimicas, composiciones y metodos. |
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-
1996
- 1996-06-05 BR BR9609066A patent/BR9609066A/pt not_active Application Discontinuation
- 1996-06-05 AU AU61577/96A patent/AU725689B2/en not_active Ceased
- 1996-06-05 RO RO97-02272A patent/RO118046B1/ro unknown
- 1996-06-05 WO PCT/US1996/009335 patent/WO1996040257A1/en not_active Ceased
- 1996-06-05 CN CNB961961554A patent/CN1142793C/zh not_active Expired - Fee Related
- 1996-06-05 CN CNA2004100027960A patent/CN1522701A/zh active Pending
- 1996-06-05 KR KR1019970709029A patent/KR100618466B1/ko not_active Expired - Fee Related
- 1996-06-05 NZ NZ310730A patent/NZ310730A/xx unknown
- 1996-06-05 CZ CZ0385097A patent/CZ297975B6/cs not_active IP Right Cessation
- 1996-06-05 IL IL12224296A patent/IL122242A/en not_active IP Right Cessation
- 1996-06-05 CA CA002224079A patent/CA2224079A1/en not_active Abandoned
- 1996-06-05 ES ES96919170T patent/ES2167571T3/es not_active Expired - Lifetime
- 1996-06-05 PT PT96919170T patent/PT831910E/pt unknown
- 1996-06-05 JP JP9501678A patent/JPH11507627A/ja not_active Ceased
- 1996-06-05 PL PL96324001A patent/PL185150B1/pl not_active IP Right Cessation
- 1996-06-05 DK DK96919170T patent/DK0831910T3/da active
- 1996-06-05 EP EP96919170A patent/EP0831910B1/en not_active Expired - Lifetime
- 1996-06-05 AT AT96919170T patent/ATE209047T1/de not_active IP Right Cessation
- 1996-06-05 DE DE69617235T patent/DE69617235T2/de not_active Expired - Fee Related
- 1996-06-05 RU RU98100250/14A patent/RU2166330C2/ru 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 |
|---|---|
| CA2224079A1 (en) | 1996-12-19 |
| RU2166330C2 (ru) | 2001-05-10 |
| ATE209047T1 (de) | 2001-12-15 |
| CN1522701A (zh) | 2004-08-25 |
| RO118046B1 (ro) | 2003-01-30 |
| PL185150B1 (pl) | 2003-03-31 |
| DK0831910T3 (da) | 2002-05-21 |
| PT831910E (pt) | 2002-05-31 |
| NO975741L (no) | 1998-01-29 |
| US6653306B1 (en) | 2003-11-25 |
| KR100618466B1 (ko) | 2006-12-13 |
| JPH11507627A (ja) | 1999-07-06 |
| BR9609066A (pt) | 1999-01-26 |
| WO1996040257A1 (en) | 1996-12-19 |
| IL122242A (en) | 2001-07-24 |
| IL122242A0 (en) | 1998-04-05 |
| KR19990022548A (ko) | 1999-03-25 |
| PL324001A1 (en) | 1998-04-27 |
| EP0831910A1 (en) | 1998-04-01 |
| NO318184B1 (no) | 2005-02-14 |
| AU725689B2 (en) | 2000-10-19 |
| CN1192697A (zh) | 1998-09-09 |
| DE69617235D1 (de) | 2002-01-03 |
| CZ297975B6 (cs) | 2007-05-09 |
| EP0831910B1 (en) | 2001-11-21 |
| CN1142793C (zh) | 2004-03-24 |
| AU6157796A (en) | 1996-12-30 |
| NZ310730A (en) | 2001-01-26 |
| CZ385097A3 (cs) | 1998-06-17 |
| NO975741D0 (no) | 1997-12-05 |
| ES2167571T3 (es) | 2002-05-16 |
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