KR19990022723A - 울혈성심부전의 치료를 위한 스피로노락톤 및 앤지오텐신 ii 길 항제 복합요법 - Google Patents
울혈성심부전의 치료를 위한 스피로노락톤 및 앤지오텐신 ii 길 항제 복합요법 Download PDFInfo
- Publication number
- KR19990022723A KR19990022723A KR1019970709165A KR19970709165A KR19990022723A KR 19990022723 A KR19990022723 A KR 19990022723A KR 1019970709165 A KR1019970709165 A KR 1019970709165A KR 19970709165 A KR19970709165 A KR 19970709165A KR 19990022723 A KR19990022723 A KR 19990022723A
- Authority
- KR
- South Korea
- Prior art keywords
- angiotensin
- receptor antagonist
- formula
- moiety
- 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.)
- Ceased
Links
- 239000002333 angiotensin II receptor antagonist Substances 0.000 title claims abstract description 192
- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 title claims abstract description 47
- 229960002256 spironolactone Drugs 0.000 title claims abstract description 39
- 206010019280 Heart failures Diseases 0.000 title claims abstract description 23
- 206010007559 Cardiac failure congestive Diseases 0.000 title claims abstract description 19
- 238000011282 treatment Methods 0.000 title claims abstract description 10
- 238000002648 combination therapy Methods 0.000 title abstract description 28
- 229940123413 Angiotensin II antagonist Drugs 0.000 title description 155
- -1 3,5-dibutyl-1H-1,2,4-triazol-1-yl Chemical group 0.000 claims abstract description 163
- 150000001875 compounds Chemical class 0.000 claims abstract description 66
- 102000003979 Mineralocorticoid Receptors Human genes 0.000 claims abstract description 43
- 108090000375 Mineralocorticoid Receptors Proteins 0.000 claims abstract description 43
- 229940044551 receptor antagonist Drugs 0.000 claims abstract description 40
- 239000002464 receptor antagonist Substances 0.000 claims abstract description 40
- 229940126317 angiotensin II receptor antagonist Drugs 0.000 claims abstract description 31
- 206010020772 Hypertension Diseases 0.000 claims abstract description 25
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 8
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 7
- 125000001425 triazolyl group Chemical group 0.000 claims abstract description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 33
- 230000002378 acidificating effect Effects 0.000 claims description 28
- 125000003118 aryl group Chemical group 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 27
- 229910052717 sulfur Inorganic materials 0.000 claims description 25
- 229910052760 oxygen Inorganic materials 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 23
- 125000000623 heterocyclic group Chemical group 0.000 claims description 21
- 239000001301 oxygen Substances 0.000 claims description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 20
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 20
- 125000004432 carbon atom Chemical group C* 0.000 claims description 20
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
- 239000002934 diuretic Substances 0.000 claims description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 18
- 125000005842 heteroatom Chemical group 0.000 claims description 18
- 125000004434 sulfur atom Chemical group 0.000 claims description 17
- 125000001145 hydrido group Chemical group *[H] 0.000 claims description 15
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 14
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 14
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 13
- 229910052799 carbon Inorganic materials 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
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 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
- 125000002924 primary amino group Chemical group [H]N([H])* 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
- 239000002253 acid Substances 0.000 claims description 11
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims description 11
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 11
- 239000004593 Epoxy Substances 0.000 claims description 10
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 10
- 125000006413 ring segment Chemical group 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- 125000001188 haloalkyl group Chemical group 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- 230000001882 diuretic effect Effects 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 125000001544 thienyl group Chemical group 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
- 125000002618 bicyclic heterocycle 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
- 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 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
- LASWNZRBIPFGHP-UHFFFAOYSA-N 2,7-diethyl-5-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]pyrazolo[1,5-b][1,2,4]triazole Chemical compound N12N=C(CC)N=C2C(CC)=CN1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=NN1 LASWNZRBIPFGHP-UHFFFAOYSA-N 0.000 claims description 6
- DNVWFUABLSEXTM-UHFFFAOYSA-N 2-[[1-(1-carboxyheptyl)imidazol-4-yl]carbamoyl]-6-hydroxybenzoic acid Chemical compound CCCCCCC(C(O)=O)N1C=NC(NC(=O)C=2C(=C(O)C=CC=2)C(O)=O)=C1 DNVWFUABLSEXTM-UHFFFAOYSA-N 0.000 claims description 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
- 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 description 6
- 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 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
- 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 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
- 239000002083 C09CA01 - Losartan Substances 0.000 claims description 6
- 239000002080 C09CA02 - Eprosartan Substances 0.000 claims description 6
- 239000004072 C09CA03 - Valsartan Substances 0.000 claims description 6
- 239000002947 C09CA04 - Irbesartan 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
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 6
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 6
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 6
- 125000005135 aryl 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
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000004122 cyclic group Chemical group 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
- 125000000457 gamma-lactone group Chemical group 0.000 claims description 6
- 125000004440 haloalkylsulfinyl group Chemical group 0.000 claims description 6
- 125000004441 haloalkylsulfonyl group Chemical group 0.000 claims description 6
- 229960002198 irbesartan Drugs 0.000 claims description 6
- 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 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
- 229960000519 losartan potassium Drugs 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 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 6
- 229920006395 saturated elastomer Polymers 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
- 229960004699 valsartan Drugs 0.000 claims description 6
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 4
- 125000005110 aryl thio group Chemical group 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 4
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- WJXAVNPIJIPGMN-PNGYUKAISA-N (2s)-2-[[(2s)-1-[(2s)-2-[[(2s,3s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-5-(diaminomethylideneamino)-2-[[2-(methylamino)acetyl]amino]pentanoyl]amino]-3-methylbutanoyl]amino]-3-(4-methoxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]py Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)CNC)C(C)C)C1=CC=C(OC)C=C1 WJXAVNPIJIPGMN-PNGYUKAISA-N 0.000 claims description 3
- 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
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 claims description 3
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 claims description 3
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 3
- 125000004506 1,2,5-oxadiazolyl group Chemical group 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
- AIGVXGCHRIOQNR-UHFFFAOYSA-N 2-butyl-5-chloro-3-[[1-[2-(2h-tetrazol-5-yl)phenyl]indol-4-yl]methyl]imidazole-4-carboxylic acid Chemical compound CCCCC1=NC(Cl)=C(C(O)=O)N1CC1=CC=CC2=C1C=CN2C1=CC=CC=C1C1=NNN=N1 AIGVXGCHRIOQNR-UHFFFAOYSA-N 0.000 claims description 3
- 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 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
- LDILUHSYQQLZRC-UHFFFAOYSA-N 5-[[[4-[2-hydroxy-3-(propan-2-ylamino)propoxy]-1h-indole-2-carbonyl]amino]methyl]-2-propyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carboxylic acid Chemical compound CCCC1=NC(CNC(=O)C=2NC3=CC=CC(OCC(O)CNC(C)C)=C3C=2)=C(C(O)=O)N1CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 LDILUHSYQQLZRC-UHFFFAOYSA-N 0.000 claims description 3
- OFYWYKMCRWMPPQ-UHFFFAOYSA-N 5-ethyl-2-propyl-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carboxylic acid Chemical compound CCCC1=NC(CC)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C2=NNN=N2)C=C1 OFYWYKMCRWMPPQ-UHFFFAOYSA-N 0.000 claims description 3
- 108010076395 CGP 38560 Proteins 0.000 claims description 3
- LINHZVMHXABQLB-ZDUSSCGKSA-N Isoboldine Chemical compound CN1CCC2=CC(OC)=C(O)C3=C2[C@@H]1CC1=C3C=C(OC)C(O)=C1 LINHZVMHXABQLB-ZDUSSCGKSA-N 0.000 claims description 3
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Classifications
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- 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
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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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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)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
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- Public Health (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Steroid Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
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| US48608995A | 1995-06-07 | 1995-06-07 | |
| US8/486089 | 1995-06-07 |
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| KR19990022723A true KR19990022723A (ko) | 1999-03-25 |
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| PT (1) | PT831911E (enExample) |
| WO (1) | WO1996040258A2 (enExample) |
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| 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 |
| MXPA02001694A (es) | 1999-08-30 | 2002-08-06 | Aventis Pharma Gmbh | Uso de inhibidores del sistema renina-angiotensina en la prevencion de eventos cardiovasculares. |
| CA2400124C (en) * | 2000-02-18 | 2010-12-14 | Kazuaki Ikeya | Tnf-.alpha. inhibitors |
| 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 |
| DE10335027A1 (de) * | 2003-07-31 | 2005-02-17 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verwendung von Angiotensin II Rezeptor Antagonisten |
| CA2520763A1 (en) | 2003-04-03 | 2004-10-21 | The Regents Of The University Of California | Improved inhibitors for the soluble epoxide 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 |
| US7662910B2 (en) | 2004-10-20 | 2010-02-16 | The Regents Of The University Of California | Inhibitors for the soluble epoxide hydrolase |
| WO2006068760A2 (en) * | 2004-11-19 | 2006-06-29 | The Regents Of The University Of California | Anti-inflammatory pyrazolopyrimidines |
| CA2909277A1 (en) | 2006-04-04 | 2007-10-11 | Kevan M. Shokat | Kinase antagonists |
| EP2051696A2 (en) * | 2006-08-18 | 2009-04-29 | 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 |
| DK2240451T3 (da) | 2008-01-04 | 2017-11-20 | Intellikine Llc | Isoquinolinonderivater substitueret med en purin, der er anvendelig som pi3k-inhibitorer |
| US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
| WO2009114874A2 (en) | 2008-03-14 | 2009-09-17 | Intellikine, Inc. | Benzothiazole kinase inhibitors and methods of use |
| EP2252293B1 (en) * | 2008-03-14 | 2018-06-27 | Intellikine, LLC | Kinase inhibitors and methods of use |
| US20110224223A1 (en) | 2008-07-08 | 2011-09-15 | The Regents Of The University Of California, A California Corporation | MTOR Modulators and Uses Thereof |
| US9096611B2 (en) | 2008-07-08 | 2015-08-04 | Intellikine Llc | Kinase inhibitors and methods of use |
| WO2010036380A1 (en) | 2008-09-26 | 2010-04-01 | Intellikine, Inc. | Heterocyclic kinase inhibitors |
| US8697709B2 (en) | 2008-10-16 | 2014-04-15 | The Regents Of The University Of California | Fused ring heteroaryl kinase inhibitors |
| US8476431B2 (en) | 2008-11-03 | 2013-07-02 | Itellikine LLC | Benzoxazole kinase inhibitors and methods of use |
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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 |
| WO1991011999A1 (en) * | 1990-02-13 | 1991-08-22 | Merck & Co., Inc. | Angiotensin ii antagonists incorporating a substituted benzyl element |
| 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 |
| US5049565A (en) * | 1990-12-07 | 1991-09-17 | Merck & Co., Inc. | Microbial transformation process for preparing anti-hypertensive products |
| EP0586513A1 (en) * | 1991-05-10 | 1994-03-16 | Merck & Co. Inc. | Acidic aralkyl triazole derivatives active as angiotensin ii antagonists |
| 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 |
| US5264447A (en) * | 1992-09-01 | 1993-11-23 | Merck & Co., Inc. | Angiotensin II antagonist |
| 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 DE DE69620756T patent/DE69620756T2/de not_active Expired - Fee Related
- 1996-06-05 AT AT96919173T patent/ATE216261T1/de not_active IP Right Cessation
- 1996-06-05 ES ES96919173T patent/ES2175098T3/es not_active Expired - Lifetime
- 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 PT PT96919173T patent/PT831911E/pt unknown
- 1996-06-05 WO PCT/US1996/009342 patent/WO1996040258A2/en not_active Ceased
- 1996-06-05 DK DK96919173T patent/DK0831911T3/da active
- 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 EP EP96919173A patent/EP0831911B1/en not_active Expired - Lifetime
- 1996-06-05 CN CN96196086A patent/CN1192696A/zh active Pending
- 1996-06-05 KR KR1019970709165A patent/KR19990022723A/ko not_active Ceased
- 1996-06-05 JP JP9501683A patent/JPH11509838A/ja not_active Abandoned
- 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
Also Published As
| Publication number | Publication date |
|---|---|
| BR9608505A (pt) | 1999-07-06 |
| EP0831911A2 (en) | 1998-04-01 |
| EP0831911B1 (en) | 2002-04-17 |
| CZ384897A3 (cs) | 1998-05-13 |
| IL122246A (en) | 2004-06-01 |
| CZ291268B6 (cs) | 2003-01-15 |
| PT831911E (pt) | 2002-09-30 |
| DE69620756T2 (de) | 2002-11-14 |
| CN1192696A (zh) | 1998-09-09 |
| DK0831911T3 (da) | 2002-07-22 |
| WO1996040258A3 (en) | 1997-01-23 |
| DE69620756D1 (de) | 2002-05-23 |
| US20040102423A1 (en) | 2004-05-27 |
| ES2175098T3 (es) | 2002-11-16 |
| WO1996040258A2 (en) | 1996-12-19 |
| ATE216261T1 (de) | 2002-05-15 |
| CA2224222A1 (en) | 1996-12-19 |
| AU6158096A (en) | 1996-12-30 |
| JPH11509838A (ja) | 1999-08-31 |
| IL122246A0 (en) | 1998-04-05 |
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