JPH11509838A - 充血性心不全症を処置するためのスピロノラクトン化合物とアンギオテンシンｉｉ拮抗物質との組合わせ治療 - Google Patents
充血性心不全症を処置するためのスピロノラクトン化合物とアンギオテンシンｉｉ拮抗物質との組合わせ治療Info
- Publication number
- JPH11509838A JPH11509838A JP9501683A JP50168397A JPH11509838A JP H11509838 A JPH11509838 A JP H11509838A JP 9501683 A JP9501683 A JP 9501683A JP 50168397 A JP50168397 A JP 50168397A JP H11509838 A JPH11509838 A JP H11509838A
- Authority
- JP
- Japan
- Prior art keywords
- group
- receptor antagonist
- angiotensin
- groups
- alkyl
- 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.)
- Abandoned
Links
- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical class 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 34
- 239000002333 angiotensin II receptor antagonist Substances 0.000 title claims abstract description 33
- 238000002648 combination therapy Methods 0.000 title claims abstract description 30
- 206010019280 Heart failures Diseases 0.000 title claims abstract description 24
- 206010007559 Cardiac failure congestive Diseases 0.000 title claims abstract description 20
- 229940123413 Angiotensin II antagonist Drugs 0.000 title description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 80
- 229940044551 receptor antagonist Drugs 0.000 claims abstract description 48
- 239000002464 receptor antagonist Substances 0.000 claims abstract description 48
- 102000003979 Mineralocorticoid Receptors Human genes 0.000 claims abstract description 41
- 108090000375 Mineralocorticoid Receptors Proteins 0.000 claims abstract description 41
- 229960002256 spironolactone Drugs 0.000 claims abstract description 28
- 229940126317 angiotensin II receptor antagonist Drugs 0.000 claims abstract description 24
- 206010020772 Hypertension Diseases 0.000 claims abstract description 20
- 239000004593 Epoxy Substances 0.000 claims abstract description 9
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 8
- 238000011282 treatment Methods 0.000 claims abstract description 7
- 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 141
- 125000000217 alkyl group Chemical group 0.000 claims description 48
- 239000005557 antagonist Substances 0.000 claims description 44
- 238000000034 method Methods 0.000 claims description 32
- 229910052760 oxygen Inorganic materials 0.000 claims description 30
- 230000002378 acidificating effect Effects 0.000 claims description 28
- 239000001301 oxygen Substances 0.000 claims description 27
- 229910052717 sulfur Inorganic materials 0.000 claims description 27
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 26
- 125000003118 aryl group Chemical group 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 26
- 125000004432 carbon atom Chemical group C* 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 20
- 125000000623 heterocyclic group Chemical group 0.000 claims description 20
- 125000004434 sulfur atom Chemical group 0.000 claims description 20
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 17
- 125000005842 heteroatom Chemical group 0.000 claims description 17
- 150000004678 hydrides Chemical class 0.000 claims description 17
- 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 claims description 16
- 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 claims description 16
- 229960002478 aldosterone Drugs 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 125000004122 cyclic group Chemical group 0.000 claims description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
- 239000002934 diuretic Substances 0.000 claims description 14
- 229940079593 drug Drugs 0.000 claims description 14
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 13
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 13
- 239000011593 sulfur Substances 0.000 claims description 13
- 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 12
- 239000004072 C09CA03 - Valsartan Substances 0.000 claims description 12
- 239000002947 C09CA04 - Irbesartan Substances 0.000 claims description 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 description 12
- 125000003368 amide group Chemical group 0.000 claims description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
- 229960002198 irbesartan Drugs 0.000 claims description 12
- 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 12
- 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 12
- 229960004699 valsartan Drugs 0.000 claims description 12
- 125000001072 heteroaryl group Chemical group 0.000 claims description 11
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 10
- 125000001544 thienyl group Chemical group 0.000 claims description 10
- 108010083387 Saralasin Proteins 0.000 claims description 9
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 9
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 9
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- 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
- 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
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 229920006395 saturated elastomer Polymers 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 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 6
- 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 6
- 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 6
- 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 6
- 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 6
- 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 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 6
- 102000008873 Angiotensin II receptor Human genes 0.000 claims description 6
- 108050000824 Angiotensin II receptor Proteins 0.000 claims description 6
- 239000002080 C09CA02 - Eprosartan Substances 0.000 claims description 6
- 239000002081 C09CA05 - Tasosartan Substances 0.000 claims description 6
- 239000002053 C09CA06 - Candesartan Substances 0.000 claims description 6
- 239000005537 C09CA07 - Telmisartan Substances 0.000 claims description 6
- 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 6
- 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 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 6
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 6
- 229960000932 candesartan Drugs 0.000 claims description 6
- 229960004349 candesartan cilexetil Drugs 0.000 claims description 6
- 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 6
- 229950006523 cilexetil Drugs 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- VTDCYOLLYVAJSY-UHFFFAOYSA-N cyclohexyl propan-2-yl carbonate Chemical compound CC(C)OC(=O)OC1CCCCC1 VTDCYOLLYVAJSY-UHFFFAOYSA-N 0.000 claims description 6
- 230000001882 diuretic effect Effects 0.000 claims description 6
- 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 6
- 229960004563 eprosartan Drugs 0.000 claims description 6
- 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 6
- 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 6
- 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 description 6
- 125000006413 ring segment Chemical group 0.000 claims description 6
- 229960001379 saralasin acetate 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
- 229960005187 telmisartan Drugs 0.000 claims description 6
- XUHRVZXFBWDCFB-QRTDKPMLSA-N (3R)-4-[[(3S,6S,9S,12R,15S,18R,21R,24R,27R,28R)-12-(3-amino-3-oxopropyl)-6-[(2S)-butan-2-yl]-3-(2-carboxyethyl)-18-(hydroxymethyl)-28-methyl-9,15,21,24-tetrakis(2-methylpropyl)-2,5,8,11,14,17,20,23,26-nonaoxo-1-oxa-4,7,10,13,16,19,22,25-octazacyclooctacos-27-yl]amino]-3-[[(2R)-2-[[(3S)-3-hydroxydecanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoic acid Chemical compound CCCCCCC[C@H](O)CC(=O)N[C@H](CC(C)C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H]1[C@@H](C)OC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CO)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC1=O)[C@@H](C)CC XUHRVZXFBWDCFB-QRTDKPMLSA-N 0.000 claims description 5
- 108010088950 Tensins Proteins 0.000 claims description 5
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 5
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 5
- 125000000457 gamma-lactone group Chemical group 0.000 claims description 5
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims description 4
- 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 4
- 150000002148 esters Chemical class 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
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 230000036961 partial effect Effects 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 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 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
- 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
- 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
- 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 3
- 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 3
- 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 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
- AWZMTWHHQXOWQR-UHFFFAOYSA-N 2-ethyl-4-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methoxy]-5,6,7,8-tetrahydroquinoline Chemical compound C=12CCCCC2=NC(CC)=CC=1OCC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 AWZMTWHHQXOWQR-UHFFFAOYSA-N 0.000 claims description 3
- 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 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
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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
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- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
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- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (3)
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| US48608995A | 1995-06-07 | 1995-06-07 | |
| US08/486,089 | 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)
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| JPH11509838A true JPH11509838A (ja) | 1999-08-31 |
| JPH11509838A5 JPH11509838A5 (enExample) | 2005-05-12 |
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| JP9501683A Abandoned JPH11509838A (ja) | 1995-06-07 | 1996-06-05 | 充血性心不全症を処置するためのスピロノラクトン化合物とアンギオテンシンｉｉ拮抗物質との組合わせ治療 |
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| US (1) | US20040102423A1 (enExample) |
| EP (1) | EP0831911B1 (enExample) |
| JP (1) | JPH11509838A (enExample) |
| KR (1) | KR19990022723A (enExample) |
| CN (1) | CN1192696A (enExample) |
| AT (1) | ATE216261T1 (enExample) |
| AU (1) | AU6158096A (enExample) |
| BR (1) | BR9608505A (enExample) |
| CA (1) | CA2224222A1 (enExample) |
| CZ (1) | CZ291268B6 (enExample) |
| DE (1) | DE69620756T2 (enExample) |
| DK (1) | DK0831911T3 (enExample) |
| ES (1) | ES2175098T3 (enExample) |
| IL (1) | IL122246A (enExample) |
| PT (1) | PT831911E (enExample) |
| WO (1) | WO1996040258A2 (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007500677A (ja) * | 2003-07-31 | 2007-01-18 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | アンギオテンシンｉｉ受容体アンタゴニストの使用 |
| JP2008517072A (ja) * | 2004-10-20 | 2008-05-22 | ザ レジェンツ オブ ザ ユニバーシティー オブ カリフォルニア | 可溶性エポキシド加水分解酵素の改良された阻害剤 |
Families Citing this family (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6306826B1 (en) | 1997-06-04 | 2001-10-23 | The Regents Of The University Of California | Treatment of heart failure with growth hormone |
| US6211217B1 (en) | 1999-03-16 | 2001-04-03 | Novartis Ag | Method for reducing pericardial fibrosis and adhesion formation |
| EE05670B1 (et) | 1999-08-30 | 2013-08-15 | Aventis Pharma Deutschland Gmbh | Ramipriil kardiovaskulaarsete haigusjuhtude rahoidmiseks |
| AU2001234088B2 (en) * | 2000-02-18 | 2005-12-01 | Takeda Pharmaceutical Company Limited | Tnf-alpha inhibitors |
| 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 |
| EP1608319A4 (en) | 2003-04-03 | 2007-02-28 | Univ California | IMPROVED HEMMER FOR SOLUBLE EPOXY HYDROLASE |
| CA2559665A1 (en) | 2004-03-16 | 2005-09-29 | The Regents Of The University Of California | Reducing nephropathy with inhibitors of soluble epoxide hydrolase and epoxyeicosanoids |
| 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 |
| KR20130087054A (ko) | 2006-04-04 | 2013-08-05 | 더 리젠트스 오브 더 유니이버시티 오브 캘리포니아 | 키나제 길항물질 |
| WO2008021666A2 (en) * | 2006-08-18 | 2008-02-21 | Morton Grove Pharmaceuticals, Inc. | Stable liquid levetiracetam compositions and methods |
| WO2009046448A1 (en) * | 2007-10-04 | 2009-04-09 | Intellikine, Inc. | 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 |
| MX358640B (es) * | 2008-01-04 | 2018-08-29 | Intellikine Llc | Isoquinolin-1 (2h) -onas y tieno [2,3-d]pirimidin-4(3h) -onas substituidas, y metodos de uso de las mismas. |
| WO2009114874A2 (en) | 2008-03-14 | 2009-09-17 | Intellikine, Inc. | Benzothiazole kinase inhibitors and methods of use |
| JP5547099B2 (ja) * | 2008-03-14 | 2014-07-09 | インテリカイン， エルエルシー | キナーゼ阻害剤および使用方法 |
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| US3257390A (en) * | 1963-06-12 | 1966-06-21 | Merck & Co Inc | Ring a unsaturated 21-hydroxy-3-oxo-17alpha-pregnane-17-carboxylic acid lactone diuretic agents |
| DE2652761C2 (de) * | 1976-11-16 | 1985-11-21 | Schering AG, 1000 Berlin und 4709 Bergkamen | 15,16-Methylen-Spirolactone, Verfahren zu deren Herstellung und diese enthaltende Arzneimittel |
| DE3506100A1 (de) * | 1985-02-18 | 1986-08-21 | Schering AG, 1000 Berlin und 4709 Bergkamen | 1(alpha).7(alpha)-dithiosubstituierte spirolactone, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
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| WO1991015206A1 (en) * | 1990-04-05 | 1991-10-17 | E.I. Du Pont De Nemours And Company | Treatment of glaucoma and ocular hypertension with imidazole angiotensin-ii receptor antagonists |
| CA2053148A1 (en) * | 1990-10-16 | 1992-04-17 | Karnail Atwal | Dihydropyrimidine derivatives |
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| US5529992A (en) * | 1992-04-21 | 1996-06-25 | Curators Of The University Of Missouri | Method for inhibiting myocardial fibrosis by administering an aldosterone antagonist which suppresses aldoster one receptors |
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| WO1994009778A1 (en) * | 1992-10-26 | 1994-05-11 | Merck & Co., Inc. | Combinations of angiotensin-ii receptor antagonists and diuretics |
| CA2125251C (en) * | 1993-06-07 | 2005-04-26 | Yoshiyuki Inada | A pharmaceutical composition for angiotensin ii-mediated diseases |
-
1996
- 1996-06-05 ES ES96919173T patent/ES2175098T3/es not_active Expired - Lifetime
- 1996-06-05 CN CN96196086A patent/CN1192696A/zh active Pending
- 1996-06-05 JP JP9501683A patent/JPH11509838A/ja not_active Abandoned
- 1996-06-05 KR KR1019970709165A patent/KR19990022723A/ko not_active Ceased
- 1996-06-05 PT PT96919173T patent/PT831911E/pt unknown
- 1996-06-05 AT AT96919173T patent/ATE216261T1/de not_active IP Right Cessation
- 1996-06-05 DK DK96919173T patent/DK0831911T3/da active
- 1996-06-05 DE DE69620756T patent/DE69620756T2/de not_active Expired - Fee Related
- 1996-06-05 WO PCT/US1996/009342 patent/WO1996040258A2/en not_active Ceased
- 1996-06-05 CA CA002224222A patent/CA2224222A1/en not_active Abandoned
- 1996-06-05 BR BR9608505A patent/BR9608505A/pt not_active Application Discontinuation
- 1996-06-05 CZ CZ19973848A patent/CZ291268B6/cs not_active IP Right Cessation
- 1996-06-05 IL IL12224696A patent/IL122246A/en not_active IP Right Cessation
- 1996-06-05 EP EP96919173A patent/EP0831911B1/en not_active Expired - Lifetime
- 1996-06-05 AU AU61580/96A patent/AU6158096A/en not_active Abandoned
-
2002
- 2002-10-15 US US10/271,362 patent/US20040102423A1/en not_active Abandoned
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007500677A (ja) * | 2003-07-31 | 2007-01-18 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | アンギオテンシンｉｉ受容体アンタゴニストの使用 |
| JP2008517072A (ja) * | 2004-10-20 | 2008-05-22 | ザ レジェンツ オブ ザ ユニバーシティー オブ カリフォルニア | 可溶性エポキシド加水分解酵素の改良された阻害剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| PT831911E (pt) | 2002-09-30 |
| IL122246A (en) | 2004-06-01 |
| KR19990022723A (ko) | 1999-03-25 |
| US20040102423A1 (en) | 2004-05-27 |
| CZ384897A3 (cs) | 1998-05-13 |
| DE69620756T2 (de) | 2002-11-14 |
| EP0831911A2 (en) | 1998-04-01 |
| WO1996040258A2 (en) | 1996-12-19 |
| CA2224222A1 (en) | 1996-12-19 |
| ATE216261T1 (de) | 2002-05-15 |
| IL122246A0 (en) | 1998-04-05 |
| AU6158096A (en) | 1996-12-30 |
| DE69620756D1 (de) | 2002-05-23 |
| CZ291268B6 (cs) | 2003-01-15 |
| ES2175098T3 (es) | 2002-11-16 |
| DK0831911T3 (da) | 2002-07-22 |
| BR9608505A (pt) | 1999-07-06 |
| EP0831911B1 (en) | 2002-04-17 |
| CN1192696A (zh) | 1998-09-09 |
| WO1996040258A3 (en) | 1997-01-23 |
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