JPH11507627A - 充血性心不全症を処置するためのエポキシ−ステロイド系アルドステロン拮抗物質とアンギオテンシンｉｉ拮抗物質との組合せ治療 - Google Patents
充血性心不全症を処置するためのエポキシ−ステロイド系アルドステロン拮抗物質とアンギオテンシンｉｉ拮抗物質との組合せ治療Info
- Publication number
- JPH11507627A JPH11507627A JP9501678A JP50167897A JPH11507627A JP H11507627 A JPH11507627 A JP H11507627A JP 9501678 A JP9501678 A JP 9501678A JP 50167897 A JP50167897 A JP 50167897A JP H11507627 A JPH11507627 A JP H11507627A
- Authority
- JP
- Japan
- Prior art keywords
- epoxy
- group
- receptor antagonist
- angiotensin
- groups
- 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.)
- Ceased
Links
- 239000002333 angiotensin II receptor antagonist Substances 0.000 title claims abstract description 39
- 238000002648 combination therapy Methods 0.000 title claims abstract description 26
- 206010019280 Heart failures Diseases 0.000 title claims abstract description 23
- 206010007559 Cardiac failure congestive Diseases 0.000 title claims abstract description 20
- 229940123413 Angiotensin II antagonist Drugs 0.000 title description 7
- 229940083712 aldosterone antagonist Drugs 0.000 title description 3
- 239000002170 aldosterone antagonist Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 75
- 229940044551 receptor antagonist Drugs 0.000 claims abstract description 39
- 239000002464 receptor antagonist Substances 0.000 claims abstract description 39
- 102000003979 Mineralocorticoid Receptors Human genes 0.000 claims abstract description 35
- 108090000375 Mineralocorticoid Receptors Proteins 0.000 claims abstract description 35
- 229940126317 angiotensin II receptor antagonist Drugs 0.000 claims abstract description 29
- 206010020772 Hypertension Diseases 0.000 claims abstract description 20
- 238000011282 treatment Methods 0.000 claims abstract description 10
- 125000003700 epoxy group Chemical class 0.000 claims abstract description 9
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 8
- 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 5
- 125000001425 triazolyl group Chemical group 0.000 claims abstract description 4
- -1 imidazoly Chemical group 0.000 claims description 146
- 239000005557 antagonist Substances 0.000 claims description 46
- 125000000217 alkyl group Chemical group 0.000 claims description 45
- 229910052760 oxygen Inorganic materials 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 29
- 230000002378 acidificating effect Effects 0.000 claims description 28
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 27
- 239000001301 oxygen Substances 0.000 claims description 27
- 125000003118 aryl group Chemical group 0.000 claims description 26
- 229910052717 sulfur Inorganic materials 0.000 claims description 26
- 239000002253 acid Substances 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims description 22
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 20
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- 150000004678 hydrides Chemical class 0.000 claims description 17
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- 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
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- 108020003175 receptors Proteins 0.000 claims description 14
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 13
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 12
- 125000003368 amide group Chemical group 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
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- 229940079593 drug Drugs 0.000 claims description 10
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- 125000001544 thienyl group Chemical group 0.000 claims description 10
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- 125000005843 halogen group Chemical group 0.000 claims description 9
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- 125000001188 haloalkyl group Chemical group 0.000 claims description 8
- 125000004441 haloalkylsulfonyl group Chemical group 0.000 claims description 8
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 7
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical class [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
- 125000000304 alkynyl group Chemical group 0.000 claims description 7
- 125000002541 furyl group Chemical group 0.000 claims description 7
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
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- 125000001424 substituent group Chemical group 0.000 claims description 7
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 6
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- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000006413 ring segment Chemical group 0.000 claims description 6
- 150000003431 steroids Chemical class 0.000 claims description 6
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 5
- 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 5
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
- 229960004785 saralasin Drugs 0.000 claims description 5
- 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 5
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical group C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 4
- 239000012634 fragment Substances 0.000 claims description 4
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 claims description 3
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 claims description 3
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 3
- 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 claims description 3
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 3
- 125000004691 alkyl thio carbonyl group Chemical group 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- 125000003435 aroyl group Chemical group 0.000 claims description 3
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 3
- 125000005110 aryl thio group Chemical group 0.000 claims description 3
- 125000004104 aryloxy group Chemical group 0.000 claims description 3
- 125000002785 azepinyl group Chemical group 0.000 claims description 3
- 125000005605 benzo group Chemical group 0.000 claims description 3
- 125000002619 bicyclic group Chemical group 0.000 claims description 3
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 claims description 3
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 3
- 125000005647 linker group Chemical group 0.000 claims description 3
- 239000003595 mist Substances 0.000 claims description 3
- 125000002757 morpholinyl group Chemical group 0.000 claims description 3
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000002971 oxazolyl group Chemical group 0.000 claims description 3
- 125000003585 oxepinyl group Chemical group 0.000 claims description 3
- 125000004043 oxo group Chemical group O=* 0.000 claims description 3
- 230000036961 partial effect Effects 0.000 claims description 3
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 claims description 3
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 3
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000005493 quinolyl group Chemical group 0.000 claims description 3
- 125000006850 spacer group Chemical group 0.000 claims description 3
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 claims description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- 125000005140 aralkylsulfonyl group Chemical group 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 2
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 2
- 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 12
- 125000000457 gamma-lactone group Chemical group 0.000 claims 12
- 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 8
- 239000005973 Carvone Substances 0.000 claims 8
- 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 8
- 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 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 4
- 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 4
- RPRNBLHRKYAXSM-UHFFFAOYSA-N 2-ethyl-4-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methoxy]-5,6,7,8-tetrahydroquinoline;hydrochloride Chemical compound Cl.C=12CCCCC2=NC(CC)=CC=1OCC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 RPRNBLHRKYAXSM-UHFFFAOYSA-N 0.000 claims 4
- 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 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 4
- 239000002080 C09CA02 - Eprosartan Substances 0.000 claims 4
- 239000004072 C09CA03 - Valsartan Substances 0.000 claims 4
- 239000002947 C09CA04 - Irbesartan Substances 0.000 claims 4
- 239000002081 C09CA05 - Tasosartan Substances 0.000 claims 4
- 239000002053 C09CA06 - Candesartan Substances 0.000 claims 4
- 239000005537 C09CA07 - Telmisartan Substances 0.000 claims 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 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 4
- 229960000932 candesartan Drugs 0.000 claims 4
- 229960004349 candesartan cilexetil Drugs 0.000 claims 4
- 229960004563 eprosartan Drugs 0.000 claims 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 4
- 229960002198 irbesartan Drugs 0.000 claims 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 4
- 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 4
- 150000004702 methyl esters Chemical class 0.000 claims 4
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims 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 class [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 4
- 229960001379 saralasin acetate Drugs 0.000 claims 4
- 229960000651 tasosartan Drugs 0.000 claims 4
- 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 4
- 229960005187 telmisartan Drugs 0.000 claims 4
- 229960004699 valsartan Drugs 0.000 claims 4
- 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
- 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 3
- 108700028065 Sar(1)-Me-Tyr(4)- angiotensin II Proteins 0.000 claims 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 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
- 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 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 2
- 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 2
- FSJCYXPMWQPVOS-UHFFFAOYSA-N 2-ethyl-4-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methoxy]quinoline Chemical compound C=12C=CC=CC2=NC(CC)=CC=1OCC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 FSJCYXPMWQPVOS-UHFFFAOYSA-N 0.000 claims 2
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Classifications
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- 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
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- A—HUMAN NECESSITIES
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P9/12—Antihypertensives
Landscapes
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- Medicinal Chemistry (AREA)
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- 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)
- 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)
Applications Claiming Priority (3)
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| US48645695A | 1995-06-07 | 1995-06-07 | |
| US08/486,456 | 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 |
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| JPH11507627A true JPH11507627A (ja) | 1999-07-06 |
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| JP9501678A Ceased JPH11507627A (ja) | 1995-06-07 | 1996-06-05 | 充血性心不全症を処置するためのエポキシ−ステロイド系アルドステロン拮抗物質とアンギオテンシンｉｉ拮抗物質との組合せ治療 |
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| EP (1) | EP0831910B1 (enExample) |
| JP (1) | JPH11507627A (enExample) |
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| BR (1) | BR9609066A (enExample) |
| CA (1) | CA2224079A1 (enExample) |
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| IL (1) | IL122242A (enExample) |
| NO (1) | NO318184B1 (enExample) |
| NZ (1) | NZ310730A (enExample) |
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| WO (1) | WO1996040257A1 (enExample) |
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| CN1249682A (zh) * | 1997-01-10 | 2000-04-05 | 麦克公司 | 用于治疗有症状的心力哀竭的血管紧张素ⅱ拮抗剂 |
| 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 |
| IL145237A0 (en) * | 1999-03-05 | 2002-06-30 | Searle & Co | 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 |
| HUP0301390A3 (en) * | 2000-06-22 | 2005-04-28 | Novartis Ag | Oral pharmaceutical composition containing valsartan |
| WO2002009759A2 (en) * | 2000-07-27 | 2002-02-07 | Pharmacia Corporation | Aldosterone antagonist and cyclooxygenase-2 inhibitor combination therapy to prevent or treat inflammation-related cardiovascular disorders |
| AU7804501A (en) * | 2000-07-27 | 2002-02-13 | Pharmacia Corp | Epoxy-steroidal aldosterone antagonist and calcium channel blocker combination therapy for treatment of congestive heart failure |
| 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 |
| ATE339197T1 (de) * | 2002-03-15 | 2006-10-15 | Novartis Ag | 4-(4-methylpiperazin-1-ylmethyl)-n-(4-methyl-3- 4-pyrimindin-3-yl)pyrimidin-2-yl-amino)phenyl)- benzamide zur behandlung von ang-ii vermittelt krankheiten |
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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 |
| WO2005039637A2 (en) * | 2003-10-17 | 2005-05-06 | Novartis Ag | Combinations of an aldosterone receptor antagonist, a diuretic and an angiotensin blocker |
| EP1750862B1 (en) | 2004-06-04 | 2011-01-05 | 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 |
| JP2008520744A (ja) | 2004-11-19 | 2008-06-19 | ザ・レジェンツ・オブ・ザ・ユニバーシティ・オブ・カリフォルニア | 抗炎症性ピラゾロピリミジン |
| 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 |
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-
1996
- 1996-06-05 CZ CZ0385097A patent/CZ297975B6/cs not_active IP Right Cessation
- 1996-06-05 RO RO97-02272A patent/RO118046B1/ro unknown
- 1996-06-05 CN CNB961961554A patent/CN1142793C/zh not_active Expired - Fee Related
- 1996-06-05 PL PL96324001A patent/PL185150B1/pl not_active IP Right Cessation
- 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 CN CNA2004100027960A patent/CN1522701A/zh active Pending
- 1996-06-05 KR KR1019970709029A patent/KR100618466B1/ko not_active Expired - Fee Related
- 1996-06-05 AU AU61577/96A patent/AU725689B2/en not_active Ceased
- 1996-06-05 IL IL12224296A patent/IL122242A/en not_active IP Right Cessation
- 1996-06-05 ES ES96919170T patent/ES2167571T3/es not_active Expired - Lifetime
- 1996-06-05 WO PCT/US1996/009335 patent/WO1996040257A1/en not_active Ceased
- 1996-06-05 CA CA002224079A patent/CA2224079A1/en not_active Abandoned
- 1996-06-05 RU RU98100250/14A patent/RU2166330C2/ru not_active IP Right Cessation
- 1996-06-05 PT PT96919170T patent/PT831910E/pt unknown
- 1996-06-05 BR BR9609066A patent/BR9609066A/pt not_active Application Discontinuation
- 1996-06-05 AT AT96919170T patent/ATE209047T1/de not_active IP Right Cessation
- 1996-06-05 DK DK96919170T patent/DK0831910T3/da active
- 1996-06-05 DE DE69617235T patent/DE69617235T2/de not_active Expired - Fee Related
- 1996-06-05 NZ NZ310730A patent/NZ310730A/xx unknown
-
1997
- 1997-01-09 US US08/781,786 patent/US6653306B1/en not_active Expired - Fee Related
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2004
- 2004-11-23 NO NO19975741A patent/NO318184B1/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IL122242A (en) | 2001-07-24 |
| IL122242A0 (en) | 1998-04-05 |
| CN1522701A (zh) | 2004-08-25 |
| ATE209047T1 (de) | 2001-12-15 |
| KR19990022548A (ko) | 1999-03-25 |
| BR9609066A (pt) | 1999-01-26 |
| CN1142793C (zh) | 2004-03-24 |
| CN1192697A (zh) | 1998-09-09 |
| NZ310730A (en) | 2001-01-26 |
| KR100618466B1 (ko) | 2006-12-13 |
| NO975741L (no) | 1998-01-29 |
| ES2167571T3 (es) | 2002-05-16 |
| EP0831910B1 (en) | 2001-11-21 |
| US6653306B1 (en) | 2003-11-25 |
| CA2224079A1 (en) | 1996-12-19 |
| DE69617235D1 (de) | 2002-01-03 |
| PT831910E (pt) | 2002-05-31 |
| RU2166330C2 (ru) | 2001-05-10 |
| RO118046B1 (ro) | 2003-01-30 |
| DE69617235T2 (de) | 2002-07-25 |
| CZ297975B6 (cs) | 2007-05-09 |
| AU725689B2 (en) | 2000-10-19 |
| CZ385097A3 (cs) | 1998-06-17 |
| NO975741D0 (no) | 1997-12-05 |
| EP0831910A1 (en) | 1998-04-01 |
| WO1996040257A1 (en) | 1996-12-19 |
| PL185150B1 (pl) | 2003-03-31 |
| NO318184B1 (no) | 2005-02-14 |
| DK0831910T3 (da) | 2002-05-21 |
| AU6157796A (en) | 1996-12-30 |
| PL324001A1 (en) | 1998-04-27 |
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