LT4854B - Bifenilsulfonamidai kaip dvigubi angiotenzino ir endotelino receptorių antagonistai - Google Patents
Bifenilsulfonamidai kaip dvigubi angiotenzino ir endotelino receptorių antagonistai Download PDFInfo
- Publication number
- LT4854B LT4854B LT2000123A LT2000123A LT4854B LT 4854 B LT4854 B LT 4854B LT 2000123 A LT2000123 A LT 2000123A LT 2000123 A LT2000123 A LT 2000123A LT 4854 B LT4854 B LT 4854B
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- Lithuania
- Prior art keywords
- methyl
- dimethyl
- biphenyl
- isoxazolyl
- oxo
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- SBXDENYROQKXBE-UHFFFAOYSA-N 2-phenylbenzenesulfonamide Chemical class NS(=O)(=O)C1=CC=CC=C1C1=CC=CC=C1 SBXDENYROQKXBE-UHFFFAOYSA-N 0.000 title claims abstract description 70
- 102000015427 Angiotensins Human genes 0.000 title description 3
- 102000010180 Endothelin receptor Human genes 0.000 title description 3
- 108050001739 Endothelin receptor Proteins 0.000 title description 3
- 230000009977 dual effect Effects 0.000 title description 3
- 108010064733 Angiotensins Proteins 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 361
- 238000000034 method Methods 0.000 claims abstract description 58
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
- 206010020772 Hypertension Diseases 0.000 claims abstract description 8
- 201000010099 disease Diseases 0.000 claims abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
- -1 1-oxopentyl Chemical group 0.000 claims description 753
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 620
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 258
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 246
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 234
- 229940124530 sulfonamide Drugs 0.000 claims description 173
- 235000010290 biphenyl Nutrition 0.000 claims description 125
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 104
- 125000000217 alkyl group Chemical group 0.000 claims description 99
- 239000001257 hydrogen Substances 0.000 claims description 67
- 229910052739 hydrogen Inorganic materials 0.000 claims description 67
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 66
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 65
- 239000002904 solvent Substances 0.000 claims description 57
- 150000002431 hydrogen Chemical class 0.000 claims description 54
- 125000003545 alkoxy group Chemical group 0.000 claims description 39
- 229910052736 halogen Inorganic materials 0.000 claims description 38
- 150000002367 halogens Chemical class 0.000 claims description 38
- 239000000460 chlorine Substances 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 32
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 31
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 30
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 22
- 125000001188 haloalkyl group Chemical group 0.000 claims description 22
- 239000004305 biphenyl Substances 0.000 claims description 21
- 229910052794 bromium Inorganic materials 0.000 claims description 19
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 18
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 17
- 125000001072 heteroaryl group Chemical group 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 14
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 13
- 229950006323 angiotensin ii Drugs 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 13
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 claims description 13
- 150000002148 esters Chemical class 0.000 claims description 13
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 11
- 125000004994 halo alkoxy alkyl group Chemical group 0.000 claims description 11
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 11
- 102000005862 Angiotensin II Human genes 0.000 claims description 10
- 101800000733 Angiotensin-2 Proteins 0.000 claims description 10
- 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 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 208000035475 disorder Diseases 0.000 claims description 10
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 claims description 10
- 108050009340 Endothelin Proteins 0.000 claims description 9
- 102000002045 Endothelin Human genes 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 9
- 230000001419 dependent effect Effects 0.000 claims description 8
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 claims description 7
- 125000004499 isoxazol-5-yl group Chemical group O1N=CC=C1* 0.000 claims description 7
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 7
- 238000006268 reductive amination reaction Methods 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
- 125000006661 (C4-C6) heterocyclic group Chemical group 0.000 claims description 5
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 5
- 238000006751 Mitsunobu reaction Methods 0.000 claims description 5
- 230000010933 acylation Effects 0.000 claims description 5
- 238000005917 acylation reaction Methods 0.000 claims description 5
- 150000001408 amides Chemical class 0.000 claims description 5
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 5
- 239000004327 boric acid Substances 0.000 claims description 5
- 230000027326 copulation Effects 0.000 claims description 5
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 5
- 238000006467 substitution reaction Methods 0.000 claims description 5
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 5
- 125000005869 (methoxyethoxy)methanyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])* 0.000 claims description 4
- UENGBOCGGKLVJJ-UHFFFAOYSA-N 2-chloro-1-(2,4-difluorophenyl)ethanone Chemical compound FC1=CC=C(C(=O)CCl)C(F)=C1 UENGBOCGGKLVJJ-UHFFFAOYSA-N 0.000 claims description 4
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 4
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 4
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 4
- 125000001425 triazolyl group Chemical group 0.000 claims description 4
- 206010019280 Heart failures Diseases 0.000 claims description 3
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 230000003213 activating effect Effects 0.000 claims description 3
- 230000001434 glomerular Effects 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 claims description 3
- SURZCVYFPAXNGN-UHFFFAOYSA-N methyl-carbamic acid ethyl ester Chemical compound CCOC(=O)NC SURZCVYFPAXNGN-UHFFFAOYSA-N 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- IDSDOGBFMPQENQ-UHFFFAOYSA-N 2-[4-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2-formylphenyl]-n-(3,4-dimethyl-1,2-oxazol-5-yl)benzenesulfonamide Chemical compound O=C1N(CC=2C=C(C=O)C(=CC=2)C=2C(=CC=CC=2)S(=O)(=O)NC2=C(C(C)=NO2)C)C(CCCC)=NC21CCCC2 IDSDOGBFMPQENQ-UHFFFAOYSA-N 0.000 claims description 2
- JTHQDJJYVYFEPX-UHFFFAOYSA-N 2-butyl-3-[[3-[[(3,4-dimethyl-1,2-oxazol-5-yl)-methylamino]methyl]-4-phenylphenyl]methyl]-1,3-diazaspiro[4.4]non-1-en-4-one Chemical compound C(CCC)C1=NC2(C(N1CC1=CC(=C(C=C1)C1=CC=CC=C1)CN(C1=C(C(=NO1)C)C)C)=O)CCCC2 JTHQDJJYVYFEPX-UHFFFAOYSA-N 0.000 claims description 2
- NKDJIJPGIVVJCN-UHFFFAOYSA-N 2-methylpropyl n-methylcarbamate Chemical compound CNC(=O)OCC(C)C NKDJIJPGIVVJCN-UHFFFAOYSA-N 0.000 claims description 2
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 2
- 201000001320 Atherosclerosis Diseases 0.000 claims description 2
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 2
- 208000037487 Endotoxemia Diseases 0.000 claims description 2
- 208000010228 Erectile Dysfunction Diseases 0.000 claims description 2
- 208000004248 Familial Primary Pulmonary Hypertension Diseases 0.000 claims description 2
- 206010057671 Female sexual dysfunction Diseases 0.000 claims description 2
- 208000032843 Hemorrhage Diseases 0.000 claims description 2
- 208000019695 Migraine disease Diseases 0.000 claims description 2
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 2
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 claims description 2
- 108090000783 Renin Proteins 0.000 claims description 2
- 102100028255 Renin Human genes 0.000 claims description 2
- 230000001154 acute effect Effects 0.000 claims description 2
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 150000001450 anions Chemical class 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 230000010261 cell growth Effects 0.000 claims description 2
- 201000001881 impotence Diseases 0.000 claims description 2
- 206010027599 migraine Diseases 0.000 claims description 2
- KXMBIKHULBVOSD-UHFFFAOYSA-N n-(4,5-dimethyl-1,2-oxazol-3-yl)-2-phenylbenzenesulfonamide Chemical compound CC1=C(C)ON=C1NS(=O)(=O)C1=CC=CC=C1C1=CC=CC=C1 KXMBIKHULBVOSD-UHFFFAOYSA-N 0.000 claims description 2
- 125000002524 organometallic group Chemical group 0.000 claims description 2
- 201000008312 primary pulmonary hypertension Diseases 0.000 claims description 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 208000037803 restenosis Diseases 0.000 claims description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
- 125000006255 cyclopropyl carbonyl group Chemical group [H]C1([H])C([H])([H])C1([H])C(*)=O 0.000 claims 10
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 5
- UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical group CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 claims 5
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 4
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims 3
- 125000006002 1,1-difluoroethyl group Chemical group 0.000 claims 2
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 2
- FFGKOKNUUYZYHF-UHFFFAOYSA-N 2-(4,5-dimethyl-1,2-oxazol-3-yl)-6-phenylbenzenesulfonamide Chemical compound CC1=C(C)ON=C1C1=CC=CC(C=2C=CC=CC=2)=C1S(N)(=O)=O FFGKOKNUUYZYHF-UHFFFAOYSA-N 0.000 claims 2
- GTKIGDZXPDCIKR-UHFFFAOYSA-N 2-phenylbenzamide Chemical compound NC(=O)C1=CC=CC=C1C1=CC=CC=C1 GTKIGDZXPDCIKR-UHFFFAOYSA-N 0.000 claims 2
- ILYSAKHOYBPSPC-UHFFFAOYSA-N 2-phenylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1=CC=CC=C1 ILYSAKHOYBPSPC-UHFFFAOYSA-N 0.000 claims 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 2
- PMXDMWBBJJQEHD-UHFFFAOYSA-N 5-[3-methoxy-2,6-dimethyl-4-[[4-phenyl-3-(3,3,3-trifluoropropyl)phenyl]methoxy]-2H-pyridin-1-yl]-3,4-dimethyl-1,2-oxazole Chemical compound CC1=NOC(=C1C)N1C(C(=C(C=C1C)OCC1=CC(=C(C=C1)C1=CC=CC=C1)CCC(F)(F)F)OC)C PMXDMWBBJJQEHD-UHFFFAOYSA-N 0.000 claims 2
- 125000006637 cyclobutyl carbonyl group Chemical group 0.000 claims 2
- WNAFVJVEADYQAI-UHFFFAOYSA-N methyl 2-phenylbenzoate Chemical compound COC(=O)C1=CC=CC=C1C1=CC=CC=C1 WNAFVJVEADYQAI-UHFFFAOYSA-N 0.000 claims 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 2
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 2
- XDEHMKQLKPZERH-BYPYZUCNSA-N (2s)-2-amino-3-methylbutanamide Chemical compound CC(C)[C@H](N)C(N)=O XDEHMKQLKPZERH-BYPYZUCNSA-N 0.000 claims 1
- LQVYLAPNXWMAQJ-UHFFFAOYSA-N 1-(3,4-dimethyl-1,2-oxazol-5-yl)-2,4-dimethyl-8-[(4-phenylphenyl)methyl]-5,6-dihydro-2H-pyrido[2,3-d]pyrimidin-7-one Chemical compound CC1=NOC(=C1C)N1C(N=C(C2=C1N(C(CC2)=O)CC2=CC=C(C=C2)C2=CC=CC=C2)C)C LQVYLAPNXWMAQJ-UHFFFAOYSA-N 0.000 claims 1
- INNGCXAJNSFBRR-UHFFFAOYSA-N 1-(4,5-dimethyl-1,2-oxazol-3-yl)-2,4-dimethyl-8-[(4-phenylphenyl)methyl]-5,6-dihydro-2H-pyrido[2,3-d]pyrimidin-7-one Chemical compound CC=1C(=NOC1C)N1C(N=C(C2=C1N(C(CC2)=O)CC2=CC=C(C=C2)C2=CC=CC=C2)C)C INNGCXAJNSFBRR-UHFFFAOYSA-N 0.000 claims 1
- NTEGHZGDMDXLHQ-UHFFFAOYSA-N 1-[[5-[[1-(4,5-dimethyl-1,2-oxazol-3-yl)-2-ethyl-5,7-dimethyl-2H-imidazo[4,5-b]pyridin-3-yl]methyl]-2-phenylphenyl]methyl]-3,3-dimethylpyrrolidin-2-one Chemical compound CC=1C(=NOC=1C)N1C(N(C2=NC(=CC(=C21)C)C)CC1=CC(=C(C=C1)C1=CC=CC=C1)CN1C(C(CC1)(C)C)=O)CC NTEGHZGDMDXLHQ-UHFFFAOYSA-N 0.000 claims 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- JTUWRWHZYZMOJF-UHFFFAOYSA-N 2-(1-methylcyclopentyl)acetamide Chemical compound NC(=O)CC1(C)CCCC1 JTUWRWHZYZMOJF-UHFFFAOYSA-N 0.000 claims 1
- WLPDLZHYIZNBKB-UHFFFAOYSA-N 2-(3,4-dimethyl-1,2-oxazol-5-yl)-6-phenylbenzenesulfonamide Chemical compound CC1=NOC(C=2C(=C(C=3C=CC=CC=3)C=CC=2)S(N)(=O)=O)=C1C WLPDLZHYIZNBKB-UHFFFAOYSA-N 0.000 claims 1
- JQZDFAVENCRGSQ-UHFFFAOYSA-N 2-[4-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2-(hydroxymethyl)phenyl]-n-(4,5-dimethyl-1,2-oxazol-3-yl)benzenesulfonamide Chemical compound O=C1N(CC=2C=C(CO)C(=CC=2)C=2C(=CC=CC=2)S(=O)(=O)NC=2C(=C(C)ON=2)C)C(CCCC)=NC21CCCC2 JQZDFAVENCRGSQ-UHFFFAOYSA-N 0.000 claims 1
- RWCUTWAIVHPLHO-UHFFFAOYSA-N 2-[4-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2-(pyrazol-1-ylmethyl)phenyl]-n-(3,4-dimethyl-1,2-oxazol-5-yl)benzenesulfonamide Chemical compound O=C1N(CC=2C=C(CN3N=CC=C3)C(=CC=2)C=2C(=CC=CC=2)S(=O)(=O)NC2=C(C(C)=NO2)C)C(CCCC)=NC21CCCC2 RWCUTWAIVHPLHO-UHFFFAOYSA-N 0.000 claims 1
- SOCXXLMIWNNNRI-UHFFFAOYSA-N 2-[4-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2-formylphenyl]-n-(4,5-dimethyl-1,2-oxazol-3-yl)benzenesulfonamide Chemical compound O=C1N(CC=2C=C(C=O)C(=CC=2)C=2C(=CC=CC=2)S(=O)(=O)NC=2C(=C(C)ON=2)C)C(CCCC)=NC21CCCC2 SOCXXLMIWNNNRI-UHFFFAOYSA-N 0.000 claims 1
- JMCQGPBILKTSCM-UHFFFAOYSA-N 2-[4-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]phenyl]-N-(3,4-dimethyl-1,2-oxazol-5-yl)-N-methylbenzenesulfonamide Chemical compound CN(S(=O)(=O)C1=C(C=CC=C1)C1=CC=C(C=C1)CN1C(=NC2(C1=O)CCCC2)CCCC)C2=C(C(=NO2)C)C JMCQGPBILKTSCM-UHFFFAOYSA-N 0.000 claims 1
- KSGKOKPBZBHCDZ-UHFFFAOYSA-N 2-[4-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]phenyl]-N-(4,5-dimethyl-1,2-oxazol-3-yl)-N-methylbenzenesulfonamide Chemical compound CN(S(=O)(=O)C1=C(C=CC=C1)C1=CC=C(C=C1)CN1C(=NC2(C1=O)CCCC2)CCCC)C2=NOC(=C2C)C KSGKOKPBZBHCDZ-UHFFFAOYSA-N 0.000 claims 1
- HDRDIUYQWRKIFA-UHFFFAOYSA-N 2-[4-[(5-acetyl-4-chloro-2-propylimidazol-1-yl)methyl]phenyl]-n-(3,4-dimethyl-1,2-oxazol-5-yl)benzenesulfonamide Chemical compound CCCC1=NC(Cl)=C(C(C)=O)N1CC1=CC=C(C=2C(=CC=CC=2)S(=O)(=O)NC2=C(C(C)=NO2)C)C=C1 HDRDIUYQWRKIFA-UHFFFAOYSA-N 0.000 claims 1
- MYLVIZOINRBDHQ-UHFFFAOYSA-N 2-[4-[(5-acetyl-4-chloro-2-propylimidazol-1-yl)methyl]phenyl]-n-(4,5-dimethyl-1,2-oxazol-3-yl)benzenesulfonamide Chemical compound CCCC1=NC(Cl)=C(C(C)=O)N1CC1=CC=C(C=2C(=CC=CC=2)S(=O)(=O)NC=2C(=C(C)ON=2)C)C=C1 MYLVIZOINRBDHQ-UHFFFAOYSA-N 0.000 claims 1
- JVENKMCALAPJPX-UHFFFAOYSA-N 2-[5-[[1-(3,4-dimethyl-1,2-oxazol-5-yl)-2-ethyl-5,7-dimethyl-2H-imidazo[4,5-b]pyridin-3-yl]methyl]-2-phenylphenyl]acetonitrile Chemical compound C(#N)CC1=C(C=CC(=C1)CN1C(N(C=2C1=NC(=CC=2C)C)C1=C(C(=NO1)C)C)CC)C1=CC=CC=C1 JVENKMCALAPJPX-UHFFFAOYSA-N 0.000 claims 1
- ZBTYPUFFEQGRMY-UHFFFAOYSA-N 2-[5-[[1-(3,4-dimethyl-1,2-oxazol-5-yl)-3-methoxy-2,6-dimethyl-2H-pyridin-4-yl]oxymethyl]-2-phenylphenyl]propan-2-ol Chemical compound CC1=NOC(=C1C)N1C(C(=C(C=C1C)OCC1=CC(=C(C=C1)C1=CC=CC=C1)C(C)(C)O)OC)C ZBTYPUFFEQGRMY-UHFFFAOYSA-N 0.000 claims 1
- SHPBODZKPBFUEI-UHFFFAOYSA-N 2-[5-[[1-(4,5-dimethyl-1,2-oxazol-3-yl)-3-methoxy-2,6-dimethyl-2H-pyridin-4-yl]oxymethyl]-2-phenylphenyl]propan-2-ol Chemical compound CC=1C(=NOC1C)N1C(C(=C(C=C1C)OCC1=CC(=C(C=C1)C1=CC=CC=C1)C(C)(C)O)OC)C SHPBODZKPBFUEI-UHFFFAOYSA-N 0.000 claims 1
- UAWDIKMZFDCXTF-UHFFFAOYSA-N 2-[[4-[2-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]phenyl]methyl-propylamino]-n-methylpyridine-3-carboxamide Chemical compound N=1C=CC=C(C(=O)NC)C=1N(CCC)CC(C=C1)=CC=C1C1=CC=CC=C1S(=O)(=O)NC=1ON=C(C)C=1C UAWDIKMZFDCXTF-UHFFFAOYSA-N 0.000 claims 1
- HHFRYVABFZFNOV-UHFFFAOYSA-N 2-[[4-[2-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]phenyl]methyl-propylamino]pyridine-3-carboxylic acid Chemical compound N=1C=CC=C(C(O)=O)C=1N(CCC)CC(C=C1)=CC=C1C1=CC=CC=C1S(=O)(=O)NC=1ON=C(C)C=1C HHFRYVABFZFNOV-UHFFFAOYSA-N 0.000 claims 1
- IKCHHLCRTPLOAT-UHFFFAOYSA-N 2-[[4-[2-[(4,5-dimethyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]phenyl]methyl-propylamino]-n-methylpyridine-3-carboxamide Chemical compound N=1C=CC=C(C(=O)NC)C=1N(CCC)CC(C=C1)=CC=C1C1=CC=CC=C1S(=O)(=O)NC1=NOC(C)=C1C IKCHHLCRTPLOAT-UHFFFAOYSA-N 0.000 claims 1
- OKCRUZOIERYSRO-UHFFFAOYSA-N 2-[[4-[2-[(4,5-dimethyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]phenyl]methyl-propylamino]pyridine-3-carboxylic acid Chemical compound N=1C=CC=C(C(O)=O)C=1N(CCC)CC(C=C1)=CC=C1C1=CC=CC=C1S(=O)(=O)NC1=NOC(C)=C1C OKCRUZOIERYSRO-UHFFFAOYSA-N 0.000 claims 1
- OPDPLJAIXFEIKZ-UHFFFAOYSA-N 2-[[5-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2-phenylphenyl]methyl-(3,4-dimethyl-1,2-oxazol-5-yl)amino]acetaldehyde Chemical compound C(CCC)C1=NC2(C(N1CC1=CC(=C(C=C1)C1=CC=CC=C1)CN(C1=C(C(=NO1)C)C)CC=O)=O)CCCC2 OPDPLJAIXFEIKZ-UHFFFAOYSA-N 0.000 claims 1
- IROKFJFUWCAYLW-UHFFFAOYSA-N 2-[[5-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2-phenylphenyl]methyl-(4,5-dimethyl-1,2-oxazol-3-yl)amino]acetaldehyde Chemical compound C(CCC)C1=NC2(C(N1CC1=CC(=C(C=C1)C1=CC=CC=C1)CN(C1=NOC(=C1C)C)CC=O)=O)CCCC2 IROKFJFUWCAYLW-UHFFFAOYSA-N 0.000 claims 1
- IWHLYJNLJPFIFN-UHFFFAOYSA-N 2-butyl-3-[[3-[[(3,4-dimethyl-1,2-oxazol-5-yl)-(2,2,2-trifluoroethyl)amino]methyl]-4-phenylphenyl]methyl]-1,3-diazaspiro[4.4]non-1-en-4-one Chemical compound C(CCC)C1=NC2(C(N1CC1=CC(=C(C=C1)C1=CC=CC=C1)CN(C1=C(C(=NO1)C)C)CC(F)(F)F)=O)CCCC2 IWHLYJNLJPFIFN-UHFFFAOYSA-N 0.000 claims 1
- SUDPNOJFFCDVJT-UHFFFAOYSA-N 2-butyl-3-[[3-[[(4,5-dimethyl-1,2-oxazol-3-yl)-methylamino]methyl]-4-phenylphenyl]methyl]-1,3-diazaspiro[4.4]non-1-en-4-one Chemical compound C(CCC)C1=NC2(C(N1CC1=CC(=C(C=C1)C1=CC=CC=C1)CN(C1=NOC(=C1C)C)C)=O)CCCC2 SUDPNOJFFCDVJT-UHFFFAOYSA-N 0.000 claims 1
- KSOOVOZETWHNBV-UHFFFAOYSA-N 2-butyl-5-chloro-3-[[4-[2-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]phenyl]methyl]imidazole-4-carboxamide Chemical compound CCCCC1=NC(Cl)=C(C(N)=O)N1CC1=CC=C(C=2C(=CC=CC=2)S(=O)(=O)NC2=C(C(C)=NO2)C)C=C1 KSOOVOZETWHNBV-UHFFFAOYSA-N 0.000 claims 1
- KDCJTASHQAOLLN-UHFFFAOYSA-N 2-butyl-5-chloro-3-[[4-[2-[(4,5-dimethyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]phenyl]methyl]imidazole-4-carboxamide Chemical compound CCCCC1=NC(Cl)=C(C(N)=O)N1CC1=CC=C(C=2C(=CC=CC=2)S(=O)(=O)NC=2C(=C(C)ON=2)C)C=C1 KDCJTASHQAOLLN-UHFFFAOYSA-N 0.000 claims 1
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- PBNBNOYWIKWPBX-UHFFFAOYSA-N 2-phenylethyl 3-[[4-[2-[(4,5-dimethyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]phenyl]methyl]-2-ethylbenzimidazole-4-carboxylate Chemical compound C=12N(CC=3C=CC(=CC=3)C=3C(=CC=CC=3)S(=O)(=O)NC=3C(=C(C)ON=3)C)C(CC)=NC2=CC=CC=1C(=O)OCCC1=CC=CC=C1 PBNBNOYWIKWPBX-UHFFFAOYSA-N 0.000 claims 1
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- KVPZXQZKQUXLKE-UHFFFAOYSA-N 3,4-dimethyl-5-[4-[(4-phenylphenyl)methoxy]-2-propyl-2H-quinolin-1-yl]-1,2-oxazole Chemical compound CC1=NOC(=C1C)N1C(C=C(C2=CC=CC=C12)OCC1=CC=C(C=C1)C1=CC=CC=C1)CCC KVPZXQZKQUXLKE-UHFFFAOYSA-N 0.000 claims 1
- AGWCMIQTYZUVLM-UHFFFAOYSA-N 3-[2-butyl-3-[[4-[2-[(4,5-dimethyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]phenyl]methyl]-4-oxoquinazolin-6-yl]-1-methyl-1-propan-2-ylurea Chemical compound CCCCC1=NC2=CC=C(NC(=O)N(C)C(C)C)C=C2C(=O)N1CC(C=C1)=CC=C1C1=CC=CC=C1S(=O)(=O)NC1=NOC(C)=C1C AGWCMIQTYZUVLM-UHFFFAOYSA-N 0.000 claims 1
- KNRLDEZBDRYBOY-UHFFFAOYSA-N 3-[2-ethyl-4-[(4-phenylphenyl)methoxy]-5,6,7,8-tetrahydro-2H-quinolin-1-yl]-4,5-dimethyl-1,2-oxazole Chemical compound CC=1C(=NOC=1C)N1C(C=C(C=2CCCCC1=2)OCC1=CC=C(C=C1)C1=CC=CC=C1)CC KNRLDEZBDRYBOY-UHFFFAOYSA-N 0.000 claims 1
- ISUWDVHBPPIKIS-UHFFFAOYSA-N 3-[2-ethyl-4-[[4-phenyl-3-(trifluoromethyl)phenyl]methoxy]-2H-quinolin-1-yl]-4,5-dimethyl-1,2-oxazole Chemical compound CC=1C(=NOC1C)N1C(C=C(C2=CC=CC=C12)OCC1=CC(=C(C=C1)C1=CC=CC=C1)C(F)(F)F)CC ISUWDVHBPPIKIS-UHFFFAOYSA-N 0.000 claims 1
- MOKHUNQEFBLVKR-UHFFFAOYSA-N 3-[3-methoxy-2,6-dimethyl-4-[(4-phenyl-3-propylphenyl)methoxy]-2H-pyridin-1-yl]-4,5-dimethyl-1,2-oxazole Chemical compound CC=1C(=NOC=1C)N1C(C(=C(C=C1C)OCC1=CC(=C(C=C1)C1=CC=CC=C1)CCC)OC)C MOKHUNQEFBLVKR-UHFFFAOYSA-N 0.000 claims 1
- HHJXGXXJHXBGTG-UHFFFAOYSA-N 3-[3-methoxy-2,6-dimethyl-4-[[4-phenyl-3-(3,3,3-trifluoropropyl)phenyl]methoxy]-2H-pyridin-1-yl]-4,5-dimethyl-1,2-oxazole Chemical compound CC=1C(=NOC=1C)N1C(C(=C(C=C1C)OCC1=CC(=C(C=C1)C1=CC=CC=C1)CCC(F)(F)F)OC)C HHJXGXXJHXBGTG-UHFFFAOYSA-N 0.000 claims 1
- JVTJSIMEDPAXKE-UHFFFAOYSA-N 3-[3-methoxy-4-[[3-(methoxymethyl)-4-phenylphenyl]methoxy]-2,6-dimethyl-2H-pyridin-1-yl]-4,5-dimethyl-1,2-oxazole Chemical compound CC=1C(=NOC=1C)N1C(C(=C(C=C1C)OCC1=CC(=C(C=C1)C1=CC=CC=C1)COC)OC)C JVTJSIMEDPAXKE-UHFFFAOYSA-N 0.000 claims 1
- IDCPAIGWLYSMAX-UHFFFAOYSA-N 3-[4-[(3-chloro-4-phenylphenyl)methoxy]-2-ethyl-2H-quinolin-1-yl]-4,5-dimethyl-1,2-oxazole Chemical compound ClC1=C(C=CC(=C1)COC1=CC(N(C2=CC=CC=C12)C1=NOC(=C1C)C)CC)C1=CC=CC=C1 IDCPAIGWLYSMAX-UHFFFAOYSA-N 0.000 claims 1
- PWFBTXUZUGJVFX-UHFFFAOYSA-N 3-[4-[(3-chloro-4-phenylphenyl)methoxy]-2-ethyl-5,6,7,8-tetrahydro-2H-quinolin-1-yl]-4,5-dimethyl-1,2-oxazole Chemical compound ClC1=C(C=CC(=C1)COC1=CC(N(C=2CCCCC1=2)C1=NOC(=C1C)C)CC)C1=CC=CC=C1 PWFBTXUZUGJVFX-UHFFFAOYSA-N 0.000 claims 1
- WTAMEJYBMZGEKT-UHFFFAOYSA-N 3-[4-[[3-(2,2-dimethylpropyl)-4-phenylphenyl]methoxy]-3-methoxy-2,6-dimethyl-2H-pyridin-1-yl]-4,5-dimethyl-1,2-oxazole Chemical compound CC=1C(=NOC=1C)N1C(C(=C(C=C1C)OCC1=CC(=C(C=C1)C1=CC=CC=C1)CC(C)(C)C)OC)C WTAMEJYBMZGEKT-UHFFFAOYSA-N 0.000 claims 1
- QALPQQGHEQFTOP-UHFFFAOYSA-N 3-[4-[[3-(2-ethoxyethyl)-4-phenylphenyl]methoxy]-3-methoxy-2,6-dimethyl-2H-pyridin-1-yl]-4,5-dimethyl-1,2-oxazole Chemical compound CC=1C(=NOC=1C)N1C(C(=C(C=C1C)OCC1=CC(=C(C=C1)C1=CC=CC=C1)CCOCC)OC)C QALPQQGHEQFTOP-UHFFFAOYSA-N 0.000 claims 1
- STFNCRWRGPQYQK-UHFFFAOYSA-N 3-[4-[[3-(2-fluoroethoxymethyl)-4-phenylphenyl]methoxy]-3-methoxy-2,6-dimethyl-2H-pyridin-1-yl]-4,5-dimethyl-1,2-oxazole Chemical compound CC=1C(=NOC=1C)N1C(C(=C(C=C1C)OCC1=CC(=C(C=C1)C1=CC=CC=C1)COCCF)OC)C STFNCRWRGPQYQK-UHFFFAOYSA-N 0.000 claims 1
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- VMZDKIVJWMIZAL-UHFFFAOYSA-N 3-[[3-chloro-4-[2-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]phenyl]methyl]-5-ethyl-2-propylimidazole-4-carboxylic acid Chemical compound CCCC1=NC(CC)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)S(=O)(=O)NC2=C(C(C)=NO2)C)C(Cl)=C1 VMZDKIVJWMIZAL-UHFFFAOYSA-N 0.000 claims 1
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- BPVMZOLHJDJXOV-UHFFFAOYSA-N 3-[[4-[2-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]phenyl]methyl]-2-ethyl-5-methylimidazole-4-carboxamide Chemical compound CCC1=NC(C)=C(C(N)=O)N1CC1=CC=C(C=2C(=CC=CC=2)S(=O)(=O)NC2=C(C(C)=NO2)C)C=C1 BPVMZOLHJDJXOV-UHFFFAOYSA-N 0.000 claims 1
- YQIIUFKHFLXJES-UHFFFAOYSA-N 3-[[4-[2-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]phenyl]methyl]-2-ethylbenzimidazole-4-carboxylic acid Chemical compound CCC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1S(=O)(=O)NC=1ON=C(C)C=1C YQIIUFKHFLXJES-UHFFFAOYSA-N 0.000 claims 1
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- CDSMAUKOUJCSSX-UHFFFAOYSA-N 3-[[4-[2-[(4,5-dimethyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]-3-[(3,3-dimethyl-2-oxopyrrolidin-1-yl)methyl]phenyl]methyl]-2-ethoxy-n,n-dimethylbenzimidazole-4-carboxamide Chemical compound CCOC1=NC2=CC=CC(C(=O)N(C)C)=C2N1CC(C=1)=CC=C(C=2C(=CC=CC=2)S(=O)(=O)NC=2C(=C(C)ON=2)C)C=1CN1CCC(C)(C)C1=O CDSMAUKOUJCSSX-UHFFFAOYSA-N 0.000 claims 1
- ZFWODATUNKDEJV-UHFFFAOYSA-N 3-[[4-[2-[(4,5-dimethyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]-3-[(3,3-dimethyl-2-oxopyrrolidin-1-yl)methyl]phenyl]methyl]-2-ethoxy-n-methylbenzimidazole-4-carboxamide Chemical compound CCOC1=NC2=CC=CC(C(=O)NC)=C2N1CC(C=1)=CC=C(C=2C(=CC=CC=2)S(=O)(=O)NC=2C(=C(C)ON=2)C)C=1CN1CCC(C)(C)C1=O ZFWODATUNKDEJV-UHFFFAOYSA-N 0.000 claims 1
- NNLJVCWOIUNIEI-UHFFFAOYSA-N 3-[[4-[2-[(4,5-dimethyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]-3-[(3,3-dimethyl-2-oxopyrrolidin-1-yl)methyl]phenyl]methyl]-2-ethoxybenzimidazole-4-carboxylic acid Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=1)=CC=C(C=2C(=CC=CC=2)S(=O)(=O)NC=2C(=C(C)ON=2)C)C=1CN1CCC(C)(C)C1=O NNLJVCWOIUNIEI-UHFFFAOYSA-N 0.000 claims 1
- INTIKAQRZCDRBI-UHFFFAOYSA-N 3-[[4-[2-[(4,5-dimethyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]phenyl]methyl]-2-ethoxy-n,n-dimethylbenzimidazole-4-carboxamide Chemical compound CCOC1=NC2=CC=CC(C(=O)N(C)C)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1S(=O)(=O)NC1=NOC(C)=C1C INTIKAQRZCDRBI-UHFFFAOYSA-N 0.000 claims 1
- QUEAZQAMFQPIOI-UHFFFAOYSA-N 3-[[4-[2-[(4,5-dimethyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]phenyl]methyl]-2-ethoxy-n-methylbenzimidazole-4-carboxamide Chemical compound CCOC1=NC2=CC=CC(C(=O)NC)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1S(=O)(=O)NC1=NOC(C)=C1C QUEAZQAMFQPIOI-UHFFFAOYSA-N 0.000 claims 1
- JTOQEOXWMOFAFU-UHFFFAOYSA-N 3-[[4-[2-[(4,5-dimethyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]phenyl]methyl]-2-ethoxybenzimidazole-4-carboxylic acid Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1S(=O)(=O)NC1=NOC(C)=C1C JTOQEOXWMOFAFU-UHFFFAOYSA-N 0.000 claims 1
- RMIAFUMCUXHLQX-UHFFFAOYSA-N 3-[[4-[2-[(4,5-dimethyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]phenyl]methyl]-2-ethyl-5-methylimidazole-4-carboxamide Chemical compound CCC1=NC(C)=C(C(N)=O)N1CC1=CC=C(C=2C(=CC=CC=2)S(=O)(=O)NC=2C(=C(C)ON=2)C)C=C1 RMIAFUMCUXHLQX-UHFFFAOYSA-N 0.000 claims 1
- KFAWBGWQMXOFHN-UHFFFAOYSA-N 3-[[4-[2-[(4,5-dimethyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]phenyl]methyl]-2-ethylbenzimidazole-4-carboxylic acid Chemical compound CCC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1S(=O)(=O)NC1=NOC(C)=C1C KFAWBGWQMXOFHN-UHFFFAOYSA-N 0.000 claims 1
- SLTTWKOOKFICRX-UHFFFAOYSA-N 3-[[4-[2-[(4,5-dimethyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]phenyl]methyl]-5-ethyl-2-propylimidazole-4-carboxamide Chemical compound CCCC1=NC(CC)=C(C(N)=O)N1CC1=CC=C(C=2C(=CC=CC=2)S(=O)(=O)NC=2C(=C(C)ON=2)C)C=C1 SLTTWKOOKFICRX-UHFFFAOYSA-N 0.000 claims 1
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- BXDZOYLPNAIDOC-UHFFFAOYSA-N N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-1-[2-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxoethyl]piperidine-4-carboxamide Chemical compound CC(C)(C)c1cnc(CSc2cnc(NC(=O)C3CCN(CC(=O)NCCOCCOCCOCCNc4cccc5C(=O)N(C6CCC(=O)NC6=O)C(=O)c45)CC3)s2)o1 BXDZOYLPNAIDOC-UHFFFAOYSA-N 0.000 claims 1
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- 125000003342 alkenyl group Chemical group 0.000 claims 1
- WOSHOXJMVPZFTG-UHFFFAOYSA-N benzyl 3-[[4-[2-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]phenyl]methyl]-2-ethylbenzimidazole-4-carboxylate Chemical compound C=12N(CC=3C=CC(=CC=3)C=3C(=CC=CC=3)S(=O)(=O)NC3=C(C(C)=NO3)C)C(CC)=NC2=CC=CC=1C(=O)OCC1=CC=CC=C1 WOSHOXJMVPZFTG-UHFFFAOYSA-N 0.000 claims 1
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims 1
- 208000020832 chronic kidney disease Diseases 0.000 claims 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 claims 1
- BFGSVQSGLQJDPT-UHFFFAOYSA-N ethyl 2-(2-phenylphenyl)acetate Chemical compound CCOC(=O)CC1=CC=CC=C1C1=CC=CC=C1 BFGSVQSGLQJDPT-UHFFFAOYSA-N 0.000 claims 1
- AIYQIAGNVJJMAN-UHFFFAOYSA-N ethyl 2-[2-[2-[(4,5-dimethyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]-5-[(2-ethyl-5,7-dimethylimidazo[4,5-b]pyridin-3-yl)methyl]phenyl]acetate Chemical compound CCOC(=O)CC1=CC(CN2C3=NC(C)=CC(C)=C3N=C2CC)=CC=C1C1=CC=CC=C1S(=O)(=O)NC1=NOC(C)=C1C AIYQIAGNVJJMAN-UHFFFAOYSA-N 0.000 claims 1
- 210000003904 glomerular cell Anatomy 0.000 claims 1
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- 125000002883 imidazolyl group Chemical group 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 208000028867 ischemia Diseases 0.000 claims 1
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- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 claims 1
- UFZXANGVAOFGJL-UHFFFAOYSA-N methyl 3-[[4-[2-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]-3-[(3,3-dimethyl-2-oxopyrrolidin-1-yl)methyl]phenyl]methyl]-2-ethoxybenzimidazole-4-carboxylate Chemical compound CCOC1=NC2=CC=CC(C(=O)OC)=C2N1CC(C=1)=CC=C(C=2C(=CC=CC=2)S(=O)(=O)NC2=C(C(C)=NO2)C)C=1CN1CCC(C)(C)C1=O UFZXANGVAOFGJL-UHFFFAOYSA-N 0.000 claims 1
- GVWNBDVESBUDMO-UHFFFAOYSA-N methyl 3-[[4-[2-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]phenyl]methyl]-2-ethoxybenzimidazole-4-carboxylate Chemical compound CCOC1=NC2=CC=CC(C(=O)OC)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1S(=O)(=O)NC=1ON=C(C)C=1C GVWNBDVESBUDMO-UHFFFAOYSA-N 0.000 claims 1
- ISWGXOAQVXWQGY-UHFFFAOYSA-N methyl 3-[[4-[2-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]phenyl]methyl]-2-ethylbenzimidazole-4-carboxylate Chemical compound CCC1=NC2=CC=CC(C(=O)OC)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1S(=O)(=O)NC=1ON=C(C)C=1C ISWGXOAQVXWQGY-UHFFFAOYSA-N 0.000 claims 1
- YTXNGJLRWDQOBM-UHFFFAOYSA-N methyl 3-[[4-[2-[(4,5-dimethyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]-3-[(3,3-dimethyl-2-oxopyrrolidin-1-yl)methyl]phenyl]methyl]-2-ethoxybenzimidazole-4-carboxylate Chemical compound CCOC1=NC2=CC=CC(C(=O)OC)=C2N1CC(C=1)=CC=C(C=2C(=CC=CC=2)S(=O)(=O)NC=2C(=C(C)ON=2)C)C=1CN1CCC(C)(C)C1=O YTXNGJLRWDQOBM-UHFFFAOYSA-N 0.000 claims 1
- XZMWDKAPFHAOTO-UHFFFAOYSA-N methyl 3-[[4-[2-[(4,5-dimethyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]phenyl]methyl]-2-ethoxybenzimidazole-4-carboxylate Chemical compound CCOC1=NC2=CC=CC(C(=O)OC)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1S(=O)(=O)NC1=NOC(C)=C1C XZMWDKAPFHAOTO-UHFFFAOYSA-N 0.000 claims 1
- RMZNWYKHMAIJSL-UHFFFAOYSA-N methyl 3-[[4-[2-[(4,5-dimethyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]phenyl]methyl]-2-ethylbenzimidazole-4-carboxylate Chemical compound CCC1=NC2=CC=CC(C(=O)OC)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1S(=O)(=O)NC1=NOC(C)=C1C RMZNWYKHMAIJSL-UHFFFAOYSA-N 0.000 claims 1
- XLCKUSNCRBAKDZ-UHFFFAOYSA-N methyl 5-chloro-3-[[4-[2-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]phenyl]methyl]-2-propylimidazole-4-carboxylate Chemical compound CCCC1=NC(Cl)=C(C(=O)OC)N1CC1=CC=C(C=2C(=CC=CC=2)S(=O)(=O)NC2=C(C(C)=NO2)C)C=C1 XLCKUSNCRBAKDZ-UHFFFAOYSA-N 0.000 claims 1
- ZEKHOXWSBSVRSS-UHFFFAOYSA-N methyl 5-chloro-3-[[4-[2-[(4,5-dimethyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]phenyl]methyl]-2-propylimidazole-4-carboxylate Chemical compound CCCC1=NC(Cl)=C(C(=O)OC)N1CC1=CC=C(C=2C(=CC=CC=2)S(=O)(=O)NC=2C(=C(C)ON=2)C)C=C1 ZEKHOXWSBSVRSS-UHFFFAOYSA-N 0.000 claims 1
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- QPRHBARTFAYHFY-UHFFFAOYSA-N n-[5-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2-[2-[(4,5-dimethyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]phenyl]-2-phenylacetamide Chemical compound O=C1N(CC=2C=C(NC(=O)CC=3C=CC=CC=3)C(=CC=2)C=2C(=CC=CC=2)S(=O)(=O)NC=2C(=C(C)ON=2)C)C(CCCC)=NC21CCCC2 QPRHBARTFAYHFY-UHFFFAOYSA-N 0.000 claims 1
- PPDFOWBKEJXMLG-UHFFFAOYSA-N n-[5-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2-[2-[(4,5-dimethyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]phenyl]-3,3-dimethylbutanamide Chemical compound O=C1N(CC=2C=C(NC(=O)CC(C)(C)C)C(=CC=2)C=2C(=CC=CC=2)S(=O)(=O)NC=2C(=C(C)ON=2)C)C(CCCC)=NC21CCCC2 PPDFOWBKEJXMLG-UHFFFAOYSA-N 0.000 claims 1
- JJLFKYFLDMZIMO-UHFFFAOYSA-N n-[[5-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2-[2-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]phenyl]methyl]-3-chloro-n-methylbenzamide Chemical compound O=C1N(CC=2C=C(CN(C)C(=O)C=3C=C(Cl)C=CC=3)C(=CC=2)C=2C(=CC=CC=2)S(=O)(=O)NC2=C(C(C)=NO2)C)C(CCCC)=NC21CCCC2 JJLFKYFLDMZIMO-UHFFFAOYSA-N 0.000 claims 1
- GDKQYWQJLZOPOA-UHFFFAOYSA-N n-[[5-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2-[2-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]phenyl]methyl]-4-fluoro-n-methylbenzamide Chemical compound O=C1N(CC=2C=C(CN(C)C(=O)C=3C=CC(F)=CC=3)C(=CC=2)C=2C(=CC=CC=2)S(=O)(=O)NC2=C(C(C)=NO2)C)C(CCCC)=NC21CCCC2 GDKQYWQJLZOPOA-UHFFFAOYSA-N 0.000 claims 1
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
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Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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US9184798P | 1998-07-06 | 1998-07-06 |
Publications (2)
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LT2000123A LT2000123A (lt) | 2001-07-25 |
LT4854B true LT4854B (lt) | 2001-11-26 |
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LT2000123A LT4854B (lt) | 1998-07-06 | 2000-12-22 | Bifenilsulfonamidai kaip dvigubi angiotenzino ir endotelino receptorių antagonistai |
LT2001004A LT4864B (lt) | 1998-07-06 | 2001-01-16 | Sapropelio trąšos ir jų gavimo būdas |
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Application Number | Title | Priority Date | Filing Date |
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LT2001004A LT4864B (lt) | 1998-07-06 | 2001-01-16 | Sapropelio trąšos ir jų gavimo būdas |
Country Status (29)
Country | Link |
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EP (2) | EP1094816B1 (de) |
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Families Citing this family (222)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6541498B2 (en) | 1993-05-20 | 2003-04-01 | Texas Biotechnology | Benzenesulfonamides and the use thereof to modulate the activity of endothelin |
CA2336714A1 (en) * | 1998-07-06 | 2000-01-13 | Bristol-Myers Squibb Company | Biphenyl sulfonamides as dual angiotensin endothelin receptor antagonists |
MY125533A (en) | 1999-12-06 | 2006-08-30 | Bristol Myers Squibb Co | Heterocyclic dihydropyrimidine compounds |
EP1237888B1 (de) * | 1999-12-15 | 2006-09-13 | Bristol-Myers Squibb Company | Biphenyl - sulfonamide als duale angiotensin - endothelin - rezeptor - antagonisten |
AU2456701A (en) * | 1999-12-31 | 2001-07-16 | Texas Biotechnology Corporation | Pharmaceutical and veterinary uses of endothelin antagonists |
US6271228B1 (en) * | 2000-04-28 | 2001-08-07 | Pfizer Inc. | Blood pressure stabilization during hemodialysis |
US7622503B2 (en) | 2000-08-24 | 2009-11-24 | University Of Tennessee Research Foundation | Selective androgen receptor modulators and methods of use thereof |
JP2004514703A (ja) * | 2000-12-01 | 2004-05-20 | ノバルティス アクチエンゲゼルシャフト | 有機化合物の組合せ剤 |
ATE544750T1 (de) | 2001-09-21 | 2012-02-15 | Bristol Myers Squibb Co | Lactamhaltige verbindungen und ihre derivate als faktor-xa-hemmer |
HUP0700151A2 (en) | 2001-10-18 | 2007-05-29 | Bristol Myers Squibb Co | Human glucagon-like-peptide-1 mimics and their use in the treatment of diabetes and related conditions |
US7238671B2 (en) | 2001-10-18 | 2007-07-03 | Bristol-Myers Squibb Company | Human glucagon-like-peptide-1 mimics and their use in the treatment of diabetes and related conditions |
US8853266B2 (en) | 2001-12-06 | 2014-10-07 | University Of Tennessee Research Foundation | Selective androgen receptor modulators for treating diabetes |
US6831102B2 (en) | 2001-12-07 | 2004-12-14 | Bristol-Myers Squibb Company | Phenyl naphthol ligands for thyroid hormone receptor |
TWI328007B (en) * | 2002-01-16 | 2010-08-01 | Astrazeneca Ab | Novel compounds |
TW200307539A (en) | 2002-02-01 | 2003-12-16 | Bristol Myers Squibb Co | Cycloalkyl inhibitors of potassium channel function |
TW200403058A (en) | 2002-04-19 | 2004-03-01 | Bristol Myers Squibb Co | Heterocyclo inhibitors of potassium channel function |
US7435824B2 (en) | 2002-04-19 | 2008-10-14 | Bristol-Myers Squibb Company | Prodrugs of potassium channel inhibitors |
US7405234B2 (en) | 2002-05-17 | 2008-07-29 | Bristol-Myers Squibb Company | Bicyclic modulators of androgen receptor function |
US7057046B2 (en) | 2002-05-20 | 2006-06-06 | Bristol-Myers Squibb Company | Lactam glycogen phosphorylase inhibitors and method of use |
MY139563A (en) | 2002-09-04 | 2009-10-30 | Bristol Myers Squibb Co | Heterocyclic aromatic compounds useful as growth hormone secretagogues |
DE60332856D1 (de) | 2002-10-23 | 2010-07-15 | Bristol Myers Squibb Co | Auf glycinnitril basierende hemmer der dipeptidylpeptidase iv |
US7098235B2 (en) | 2002-11-14 | 2006-08-29 | Bristol-Myers Squibb Co. | Triglyceride and triglyceride-like prodrugs of glycogen phosphorylase inhibiting compounds |
TW200504021A (en) | 2003-01-24 | 2005-02-01 | Bristol Myers Squibb Co | Substituted anilide ligands for the thyroid receptor |
US6846836B2 (en) | 2003-04-18 | 2005-01-25 | Bristol-Myers Squibb Company | N-substituted phenylurea inhibitors of mitochondrial F1F0 ATP hydrolase |
US7557143B2 (en) | 2003-04-18 | 2009-07-07 | Bristol-Myers Squibb Company | Thyroid receptor ligands |
US6995183B2 (en) | 2003-08-01 | 2006-02-07 | Bristol Myers Squibb Company | Adamantylglycine-based inhibitors of dipeptidyl peptidase IV and methods |
US7820702B2 (en) | 2004-02-04 | 2010-10-26 | Bristol-Myers Squibb Company | Sulfonylpyrrolidine modulators of androgen receptor function and method |
US7378426B2 (en) | 2004-03-01 | 2008-05-27 | Bristol-Myers Squibb Company | Fused heterotricyclic compounds as inhibitors of 17β-hydroxysteroid dehydrogenase 3 |
US7696241B2 (en) | 2004-03-04 | 2010-04-13 | Bristol-Myers Squibb Company | Bicyclic compounds as modulators of androgen receptor function and method |
US7625923B2 (en) | 2004-03-04 | 2009-12-01 | Bristol-Myers Squibb Company | Bicyclic modulators of androgen receptor function |
US7772232B2 (en) | 2004-04-15 | 2010-08-10 | Bristol-Myers Squibb Company | Quinazolinyl compounds as inhibitors of potassium channel function |
US7550499B2 (en) | 2004-05-12 | 2009-06-23 | Bristol-Myers Squibb Company | Urea antagonists of P2Y1 receptor useful in the treatment of thrombotic conditions |
US9884038B2 (en) | 2004-06-07 | 2018-02-06 | University Of Tennessee Research Foundation | Selective androgen receptor modulator and methods of use thereof |
US9889110B2 (en) | 2004-06-07 | 2018-02-13 | University Of Tennessee Research Foundation | Selective androgen receptor modulator for treating hormone-related conditions |
US7145040B2 (en) | 2004-07-02 | 2006-12-05 | Bristol-Myers Squibb Co. | Process for the preparation of amino acids useful in the preparation of peptide receptor modulators |
TW200611704A (en) | 2004-07-02 | 2006-04-16 | Bristol Myers Squibb Co | Human glucagon-like-peptide-1 modulators and their use in the treatment of diabetes and related conditions |
US7534763B2 (en) | 2004-07-02 | 2009-05-19 | Bristol-Myers Squibb Company | Sustained release GLP-1 receptor modulators |
US7572805B2 (en) | 2004-07-14 | 2009-08-11 | Bristol-Myers Squibb Company | Pyrrolo(oxo)isoquinolines as 5HT ligands |
US7429611B2 (en) | 2004-09-23 | 2008-09-30 | Bristol-Myers Squibb Company | Indole inhibitors of 15-lipoxygenase |
AR051446A1 (es) | 2004-09-23 | 2007-01-17 | Bristol Myers Squibb Co | Glucosidos de c-arilo como inhibidores selectivos de transportadores de glucosa (sglt2) |
US7754755B2 (en) | 2004-09-23 | 2010-07-13 | Bristol-Myers Squibb Company | Inhibitors of 15-lipoxygenase |
US8143425B2 (en) | 2004-10-12 | 2012-03-27 | Bristol-Myers Squibb Company | Heterocyclic aromatic compounds useful as growth hormone secretagogues |
US7517991B2 (en) | 2004-10-12 | 2009-04-14 | Bristol-Myers Squibb Company | N-sulfonylpiperidine cannabinoid receptor 1 antagonists |
US7446210B2 (en) | 2004-10-26 | 2008-11-04 | Janssen Pharmaceutica N.V. | Factor Xa compounds |
US7589088B2 (en) | 2004-12-29 | 2009-09-15 | Bristol-Myers Squibb Company | Pyrimidine-based inhibitors of dipeptidyl peptidase IV and methods |
US7635699B2 (en) | 2004-12-29 | 2009-12-22 | Bristol-Myers Squibb Company | Azolopyrimidine-based inhibitors of dipeptidyl peptidase IV and methods |
US7361766B2 (en) | 2005-01-12 | 2008-04-22 | Bristol-Myers Squibb Company | Bicyclic heterocycles as cannabinoid receptor modulators |
WO2006076597A1 (en) | 2005-01-12 | 2006-07-20 | Bristol-Myers Squibb Company | Bicyclic heterocycles as cannabinoid receptor modulators |
US7314882B2 (en) | 2005-01-12 | 2008-01-01 | Bristol-Myers Squibb Company | Bicyclic heterocycles as cannabinoid receptor modulators |
CN101137412B (zh) | 2005-01-13 | 2012-11-07 | 布里斯托尔-迈尔斯·斯奎布公司 | 用作凝血因子XIa抑制剂的取代的二芳基化合物 |
US20060160850A1 (en) | 2005-01-18 | 2006-07-20 | Chongqing Sun | Bicyclic heterocycles as cannabinoid receptor modulators |
EP1954696B1 (de) | 2005-01-19 | 2011-02-23 | Bristol-Myers Squibb Company | 2-phenoxy-n-(1,3,4-thiadizol-2-yl)pyridin-3-aminderivate und verwandte verbindungen als p2y1-rezeptor-hemmer zur behandlung thromboembolischer erkrankungen |
ATE421518T1 (de) | 2005-02-10 | 2009-02-15 | Bristol Myers Squibb Co | Dihydrochinazolinone als 5ht-modulatoren |
US20060235028A1 (en) | 2005-04-14 | 2006-10-19 | Li James J | Inhibitors of 11-beta hydroxysteroid dehydrogenase type I |
US7521557B2 (en) | 2005-05-20 | 2009-04-21 | Bristol-Myers Squibb Company | Pyrrolopyridine-based inhibitors of dipeptidyl peptidase IV and methods |
US7317012B2 (en) | 2005-06-17 | 2008-01-08 | Bristol-Myers Squibb Company | Bicyclic heterocycles as cannabinoind-1 receptor modulators |
US7629342B2 (en) | 2005-06-17 | 2009-12-08 | Bristol-Myers Squibb Company | Azabicyclic heterocycles as cannabinoid receptor modulators |
US7572808B2 (en) | 2005-06-17 | 2009-08-11 | Bristol-Myers Squibb Company | Triazolopyridine cannabinoid receptor 1 antagonists |
US7452892B2 (en) | 2005-06-17 | 2008-11-18 | Bristol-Myers Squibb Company | Triazolopyrimidine cannabinoid receptor 1 antagonists |
US7632837B2 (en) | 2005-06-17 | 2009-12-15 | Bristol-Myers Squibb Company | Bicyclic heterocycles as cannabinoid-1 receptor modulators |
WO2007002634A1 (en) | 2005-06-27 | 2007-01-04 | Bristol-Myers Squibb Company | Carbocycle and heterocycle antagonists of p2y1 receptor useful in the treatment of thrombotic conditions |
ATE502924T1 (de) | 2005-06-27 | 2011-04-15 | Bristol Myers Squibb Co | Lineare harnstoffmimetika-antagonisten des p2y1- rezeptors zur behandlung von thromboseleiden |
US7700620B2 (en) | 2005-06-27 | 2010-04-20 | Bristol-Myers Squibb Company | C-linked cyclic antagonists of P2Y1 receptor useful in the treatment of thrombotic conditions |
AU2006261828A1 (en) | 2005-06-27 | 2007-01-04 | Bristol-Myers Squibb Company | N-linked heterocyclic antagonists of P2Y1 receptor useful in the treatment of thrombotic conditions |
US20070117987A1 (en) * | 2005-07-05 | 2007-05-24 | Viviana Braude | Process for preparing valsartan |
EP1757290A1 (de) | 2005-08-16 | 2007-02-28 | Zentaris GmbH | Triazolderivate als Liganden der Wachstumshormonrezeptoren |
US7534804B2 (en) | 2005-08-24 | 2009-05-19 | Bristol-Myers Squibb Company | Benzoxazole inhibitors of 15-lipoxygenase |
US7795436B2 (en) | 2005-08-24 | 2010-09-14 | Bristol-Myers Squibb Company | Substituted tricyclic heterocycles as serotonin receptor agonists and antagonists |
WO2007027582A2 (en) | 2005-08-31 | 2007-03-08 | University Of Tennessee Research Foundation | Treating renal disease, burns, wounds and spinal cord injury with selective androgen receptor modulators |
US8618115B2 (en) | 2005-10-26 | 2013-12-31 | Bristol-Myers Squibb Company | Substituted thieno[3,2-d]pyrimidinones as MCHR1 antagonists and methods for using them |
US7488725B2 (en) | 2005-10-31 | 2009-02-10 | Bristol-Myers Squibb Co. | Pyrrolidinyl beta-amino amide-based inhibitors of dipeptidyl peptidase IV and methods |
US7553836B2 (en) | 2006-02-06 | 2009-06-30 | Bristol-Myers Squibb Company | Melanin concentrating hormone receptor-1 antagonists |
CN101437818A (zh) * | 2006-03-03 | 2009-05-20 | 托伦特药物有限公司 | At1和eta受体的新的双重作用受体拮抗剂(dara) |
WO2007109456A2 (en) * | 2006-03-16 | 2007-09-27 | Pharmacopeia, Inc. | Substituted biphenyl isoxazole sulfonamides as dual angiotensin endothelin receptor antagonists |
EP2021014A1 (de) | 2006-05-26 | 2009-02-11 | Brystol-Myers Squibb Company | Glp-1-rezeptor-modulatoren mit verzögerter freisetzung |
US7919598B2 (en) | 2006-06-28 | 2011-04-05 | Bristol-Myers Squibb Company | Crystal structures of SGLT2 inhibitors and processes for preparing same |
PT2038252T (pt) | 2006-07-12 | 2016-12-16 | Univ Tennessee Res Found | Acilanilidos substituidos e métodos de utilização dos mesmos |
US7727978B2 (en) | 2006-08-24 | 2010-06-01 | Bristol-Myers Squibb Company | Cyclic 11-beta hydroxysteroid dehydrogenase type I inhibitors |
MX2009003658A (es) | 2006-10-05 | 2009-04-22 | Cv Therapeutics Inc | Compuestos heterociclicos que contienen nitrogeno biciclico para utilizarse como inhibidores de desaturasa de estearoilo-coa. |
US7960569B2 (en) | 2006-10-17 | 2011-06-14 | Bristol-Myers Squibb Company | Indole antagonists of P2Y1 receptor useful in the treatment of thrombotic conditions |
MX2009007831A (es) | 2007-01-22 | 2010-01-15 | Gtx Inc | Agentes de union de receptor nuclear. |
US9623021B2 (en) | 2007-01-22 | 2017-04-18 | Gtx, Inc. | Nuclear receptor binding agents |
US9604931B2 (en) | 2007-01-22 | 2017-03-28 | Gtx, Inc. | Nuclear receptor binding agents |
TW200838501A (en) * | 2007-02-02 | 2008-10-01 | Theravance Inc | Dual-acting antihypertensive agents |
PE20090185A1 (es) | 2007-03-22 | 2009-02-28 | Bristol Myers Squibb Co | Formulaciones farmaceuticas que contienen un inhibidor sglt2 |
US20080255161A1 (en) * | 2007-04-11 | 2008-10-16 | Dmitry Koltun | 3-HYDROQUINAZOLIN-4-ONE DERIVATIVES FOR USE AS STEAROYL CoA DESATURASE INHIBITORS |
EP2474549A1 (de) | 2007-04-17 | 2012-07-11 | Bristol-Myers Squibb Company | Kondensierte heterocyclische als Hemmer des 11-Beta-Hydroxysteroid-Dehydrogenase-Typ I |
PE20090696A1 (es) | 2007-04-20 | 2009-06-20 | Bristol Myers Squibb Co | Formas cristalinas de saxagliptina y procesos para preparar las mismas |
CN101663293B (zh) | 2007-04-23 | 2013-07-31 | 塞诺菲-安万特股份有限公司 | 作为p2y12拮抗剂的喹啉-甲酰胺衍生物 |
TWI448284B (zh) | 2007-04-24 | 2014-08-11 | Theravance Inc | 雙效抗高血壓劑 |
WO2008137435A1 (en) | 2007-05-04 | 2008-11-13 | Bristol-Myers Squibb Company | [6,6] and [6,7]-bicyclic gpr119 g protein-coupled receptor agonists |
CN101668759A (zh) | 2007-05-04 | 2010-03-10 | 百时美施贵宝公司 | [6,5]-双环gpr119g蛋白-偶合受体激动剂 |
TWI406850B (zh) | 2007-06-05 | 2013-09-01 | Theravance Inc | 雙效苯并咪唑抗高血壓劑 |
US20090011994A1 (en) | 2007-07-06 | 2009-01-08 | Bristol-Myers Squibb Company | Non-basic melanin concentrating hormone receptor-1 antagonists and methods |
EA016595B1 (ru) | 2007-07-17 | 2012-06-29 | Бристол-Маерс Сквибб Компани | Способ модулирования рецептора gpr119, сопряженного с g-белком, и используемые при этом соединения |
JP2010534722A (ja) | 2007-07-27 | 2010-11-11 | ブリストル−マイヤーズ スクイブ カンパニー | 新規グルコキナーゼ活性化薬およびその使用方法 |
US7834041B2 (en) | 2007-09-07 | 2010-11-16 | Theravance, Inc. | Dual-acting antihypertensive agents |
US7968603B2 (en) | 2007-09-11 | 2011-06-28 | University Of Tennessee Research Foundation | Solid forms of selective androgen receptor modulators |
WO2009038974A1 (en) | 2007-09-20 | 2009-03-26 | Irm Llc | Compounds and compositions as modulators of gpr119 activity |
JP2011506459A (ja) | 2007-12-11 | 2011-03-03 | セラヴァンス, インコーポレーテッド | 抗高血圧剤としての二重作用性ベンゾイミダゾール誘導体およびその使用 |
JP5504171B2 (ja) | 2007-12-26 | 2014-05-28 | サノフイ | P2y12アンタゴニストとしてのヘテロサイクリックピラゾール−カルボキサミド |
EP2103602A1 (de) | 2008-03-17 | 2009-09-23 | AEterna Zentaris GmbH | Neuartige 1,2,4-Triazol-Derivate und Herstellungsverfahren dafür |
JP2011518884A (ja) | 2008-04-29 | 2011-06-30 | セラヴァンス, インコーポレーテッド | 二重活性抗高血圧剤 |
CN102099340A (zh) | 2008-05-19 | 2011-06-15 | 先灵公司 | 作为因子ixa抑制剂的杂环化合物 |
PE20091928A1 (es) | 2008-05-29 | 2009-12-31 | Bristol Myers Squibb Co | Tienopirimidinas hidroxisustituidas como antagonistas de receptor-1 de hormona concentradora de melanina no basicos |
WO2009155448A1 (en) * | 2008-06-20 | 2009-12-23 | Ligand Pharmaceuticals Inc. | Biphenyl sulfonamides as dual angiotensin endothelin receptor antagonists |
TW201006821A (en) | 2008-07-16 | 2010-02-16 | Bristol Myers Squibb Co | Pyridone and pyridazone analogues as GPR119 modulators |
WO2010011821A2 (en) | 2008-07-24 | 2010-01-28 | Theravance, Inc. | Dual-acting antihypertensive agents |
US8557983B2 (en) | 2008-12-04 | 2013-10-15 | Abbvie Inc. | Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases |
US20100160322A1 (en) | 2008-12-04 | 2010-06-24 | Abbott Laboratories | Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases |
US8563735B2 (en) | 2008-12-05 | 2013-10-22 | Abbvie Inc. | Bcl-2-selective apoptosis-inducing agents for the treatment of cancer and immune diseases |
US8586754B2 (en) | 2008-12-05 | 2013-11-19 | Abbvie Inc. | BCL-2-selective apoptosis-inducing agents for the treatment of cancer and immune diseases |
EP2409977A4 (de) * | 2009-03-17 | 2012-09-26 | Daiichi Sankyo Co Ltd | Amidderivat |
CA2756786A1 (en) | 2009-03-27 | 2010-09-30 | Bristol-Myers Squibb Company | Methods for preventing major adverse cardiovascular events with dpp-iv inhibitors |
HUE049450T2 (hu) * | 2009-03-31 | 2020-09-28 | Ligand Pharm Inc | Endotelin és angiotenzin II receptor antagonista bifenilszulfonamid glomeruloszklerózis és IgA által kiváltott nefropátia kezelésére |
US20220315555A1 (en) | 2009-05-26 | 2022-10-06 | Abbvie Inc. | Apoptosis inducing agents for the treatment of cancer and immune and autoimmune diseases |
SG10201704742YA (en) * | 2009-05-26 | 2017-07-28 | Abbvie Ireland Unlimited Co | Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases |
US9034875B2 (en) | 2009-05-26 | 2015-05-19 | Abbvie Inc. | Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases |
US8546399B2 (en) | 2009-05-26 | 2013-10-01 | Abbvie Inc. | Apoptosis inducing agents for the treatment of cancer and immune and autoimmune diseases |
EP2442791B1 (de) | 2009-06-16 | 2019-11-27 | Pfizer Inc. | Darreichungsformen von apixaban |
US7956054B2 (en) | 2009-07-07 | 2011-06-07 | Theravance, Inc. | Dual-acting pyrazole antihypertensive agents |
WO2011011232A1 (en) | 2009-07-22 | 2011-01-27 | Theravance, Inc. | Dual-acting oxazole antihypertensive agents |
WO2011014520A2 (en) | 2009-07-29 | 2011-02-03 | Irm Llc | Compounds and compositions as modulators of gpr119 activity |
EP2462123B1 (de) | 2009-08-04 | 2013-10-02 | Merck Sharp & Dohme Corp. | 4,5,6-trisubstituierte pyrimidin- derivate als factor ixa inhibitoren |
CA2774573A1 (en) | 2009-10-09 | 2011-04-14 | Irm Llc | Compounds and compositions as modulators of gpr119 activity |
DK2498759T3 (en) | 2009-11-13 | 2018-11-26 | Astrazeneca Ab | TABLE FORMULATIONS WITH IMMEDIATE RELEASE |
JP5775522B2 (ja) | 2009-11-13 | 2015-09-09 | アストラゼネカ・アクチエボラーグAstrazeneca Aktiebolag | 二層錠製剤 |
RU2564901C2 (ru) | 2009-11-13 | 2015-10-10 | Бристол-Майерс Сквибб Кампани | Композиции метформина с уменьшенной массой |
CN101891735B (zh) * | 2009-11-25 | 2012-07-18 | 北京理工大学 | 联苯磺胺异噁唑类化合物、合成方法及用途 |
CN101921265B (zh) * | 2009-11-25 | 2012-07-04 | 北京理工大学 | 联苯酰胺四唑类化合物、合成方法及用途 |
US8394858B2 (en) | 2009-12-03 | 2013-03-12 | Novartis Ag | Cyclohexane derivatives and uses thereof |
JP2013517295A (ja) | 2010-01-19 | 2013-05-16 | セラヴァンス, インコーポレーテッド | 二重に作用するチオフェン、ピロール、チアゾールおよびフラン抗高血圧症薬 |
TWI562775B (en) | 2010-03-02 | 2016-12-21 | Lexicon Pharmaceuticals Inc | Methods of using inhibitors of sodium-glucose cotransporters 1 and 2 |
JP2013523822A (ja) | 2010-04-08 | 2013-06-17 | ブリストル−マイヤーズ スクイブ カンパニー | Gpr119修飾因子としてのピリミジニルピペリジニルオキシピリジノ類似体 |
JP2013523894A (ja) | 2010-04-14 | 2013-06-17 | ブリストル−マイヤーズ スクイブ カンパニー | 新規グルコキナーゼアクチベーターおよびその使用方法 |
WO2011140160A1 (en) | 2010-05-06 | 2011-11-10 | Bristol-Myers Squibb Company | Bicyclic heteroaryl compounds as gpr119 modulators |
WO2011140161A1 (en) | 2010-05-06 | 2011-11-10 | Bristol-Myers Squibb Company | Benzofuranyl analogues as gpr119 modulators |
US8697739B2 (en) | 2010-07-29 | 2014-04-15 | Novartis Ag | Bicyclic acetyl-CoA carboxylase inhibitors and uses thereof |
EP2431035A1 (de) | 2010-09-16 | 2012-03-21 | Æterna Zentaris GmbH | Neue Triazolderivate mit verbesserter Rezeptoraktivität und Bioverfügbarkeitseigenschaften als Ghrelin-Antagonisten der Wachstumshormon-Sekretagogum-Rezeptoren |
CA2811805A1 (en) | 2010-10-29 | 2012-05-03 | Abbvie Inc. | Solid dispersions containing an apoptosis-inducing agent |
UA113500C2 (xx) | 2010-10-29 | 2017-02-10 | Одержані екструзією розплаву тверді дисперсії, що містять індукуючий апоптоз засіб | |
CN103402521B (zh) | 2010-11-23 | 2016-01-20 | 艾伯维巴哈马有限公司 | 使用选择性的bcl-2抑制剂的治疗方法 |
CN107266435A (zh) | 2010-11-23 | 2017-10-20 | Abbvie 公司 | 细胞凋亡诱导剂的盐和晶形 |
ES2581323T3 (es) | 2010-12-23 | 2016-09-05 | Purdue Pharma Lp | Formas de dosificación oral sólida resistentes a alteraciones |
TWI631963B (zh) | 2011-01-05 | 2018-08-11 | 雷西肯製藥股份有限公司 | 包含鈉-葡萄糖共同輸送體1與2之抑制劑的組合物與應用方法 |
WO2013068875A1 (en) | 2011-11-11 | 2013-05-16 | Pfizer Inc. | 2-thiopyrimidinones |
EP2834238B1 (de) | 2012-04-06 | 2017-02-01 | Pfizer Inc. | Diacylglycerol-acyltransferase-2-hemmer |
US9174965B2 (en) | 2012-05-16 | 2015-11-03 | Bristol-Myers Squibb Company | Pyrimidinylpiperidinyloxypyridone analogues as GPR119 modulators |
ES2675314T3 (es) | 2012-06-11 | 2018-07-10 | Bristol-Myers Squibb Company | Profármacos de ácido fosforamídico de 5-[5-fenil-4-(piridin-2-ilmetilamino) quinazolin-2-il] piridin-3-sulfonamida |
US9969683B2 (en) | 2012-07-13 | 2018-05-15 | Gtx, Inc. | Method of treating estrogen receptor (ER)-positive breast cancers with selective androgen receptor modulator (SARMS) |
US10987334B2 (en) | 2012-07-13 | 2021-04-27 | University Of Tennessee Research Foundation | Method of treating ER mutant expressing breast cancers with selective androgen receptor modulators (SARMs) |
IN2015DN01046A (de) | 2012-07-13 | 2015-06-26 | Gtx Inc | |
US10258596B2 (en) | 2012-07-13 | 2019-04-16 | Gtx, Inc. | Method of treating HER2-positive breast cancers with selective androgen receptor modulators (SARMS) |
US10314807B2 (en) | 2012-07-13 | 2019-06-11 | Gtx, Inc. | Method of treating HER2-positive breast cancers with selective androgen receptor modulators (SARMS) |
US9744149B2 (en) | 2012-07-13 | 2017-08-29 | Gtx, Inc. | Method of treating androgen receptor (AR)-positive breast cancers with selective androgen receptor modulator (SARMs) |
US9622992B2 (en) | 2012-07-13 | 2017-04-18 | Gtx, Inc. | Method of treating androgen receptor (AR)-positive breast cancers with selective androgen receptor modulator (SARMs) |
LT6043B (lt) | 2012-08-27 | 2014-06-25 | Uab "Mibarsas" | Organinės trąšos sapropelio pagrindu ir jų gamybos būdas |
US9499482B2 (en) | 2012-09-05 | 2016-11-22 | Bristol-Myers Squibb Company | Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists |
WO2014039411A1 (en) | 2012-09-05 | 2014-03-13 | Bristol-Myers Squibb Company | Pyrrolone or pyrrolidinone melanin concentrating hormore receptor-1 antagonists |
WO2014052619A1 (en) | 2012-09-27 | 2014-04-03 | Irm Llc | Piperidine derivatives and compositions as modulators of gpr119 activity |
MX365753B (es) | 2012-11-20 | 2019-06-12 | Lexicon Pharmaceuticals Inc | Inhibidores del contransportador 1 de sodio glucosa. |
JP6386527B2 (ja) | 2013-03-11 | 2018-09-05 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | カリウムイオンチャネル阻害剤としてのピロロピリダジン |
WO2014143609A1 (en) | 2013-03-11 | 2014-09-18 | Bristol-Myers Squibb Company | Isoquinolines as potassium ion channel inhibitors |
US9050345B2 (en) | 2013-03-11 | 2015-06-09 | Bristol-Myers Squibb Company | Pyrrolotriazines as potassium ion channel inhibitors |
JP6395798B2 (ja) | 2013-03-11 | 2018-09-26 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | カリウムイオンチャネル阻害剤としてのピロロトリアジン |
US9242966B2 (en) | 2013-03-11 | 2016-01-26 | Bristol-Myers Squibb Company | Phthalazines as potassium ion channel inhibitors |
US20140275082A1 (en) | 2013-03-14 | 2014-09-18 | Abbvie Inc. | Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases |
JP6480909B2 (ja) | 2013-03-15 | 2019-03-13 | ユニバーシティー オブ サウザン カリフォルニア | アンギオテンシン関連疾患の処置のための方法、化合物および組成物 |
WO2015052610A1 (en) | 2013-10-09 | 2015-04-16 | Pfizer Inc. | Antagonists of prostaglandin ep3 receptor |
WO2015061272A1 (en) | 2013-10-22 | 2015-04-30 | Bristol-Myers Squibb Company | Isotopically labeled triazolopyridine 11-beta hydroxysteroid dehydrogenase type i inhibitors |
MA39753B1 (fr) | 2014-03-17 | 2018-10-31 | Pfizer | Inhibiteurs de diacylglycérol acyltransférase pour le traitement de troubles métaboliques ou analogues |
PE20161251A1 (es) | 2014-04-04 | 2016-11-30 | Pfizer | Compuestos heteroarilo o arilo biciclicos fusionados y su uso como inhibidores de irak4 |
US9969724B2 (en) | 2014-04-16 | 2018-05-15 | Merck Sharp & Dohme Corp. | Factor IXa inhibitors |
US10328082B2 (en) | 2014-05-30 | 2019-06-25 | Pfizer Inc. | Methods of use and combinations |
EP3237401B1 (de) | 2014-12-22 | 2019-03-06 | Pfizer Inc | Antagonisten des prostaglandin-ep3-rezeptors |
CN104761548B (zh) * | 2015-04-27 | 2017-09-12 | 梯尔希(南京)药物研发有限公司 | 一种稳定同位素标记的二苯基磺酰胺类药物的制备方法 |
CR20170498A (es) | 2015-05-05 | 2018-01-26 | Pfizer | 2-tiopirimidinonas |
EP3303303A1 (de) | 2015-05-29 | 2018-04-11 | Pfizer Inc | Neuartige heterocyclische verbindungen als vanin-1-enzym-inhibitoren |
DK3766885T3 (da) | 2015-06-17 | 2022-08-01 | Pfizer | Tricykliske forbindelser og deres anvendelse som phoshodiesteraseinhibitorer |
WO2016203335A1 (en) | 2015-06-18 | 2016-12-22 | Pfizer Inc. | Novel pyrido[2,3-b]pyrazinones as bet-family bromodomain inhibitors |
BR112018002071A2 (pt) | 2015-08-13 | 2018-09-18 | Pfizer | compostos heteroarílicos ou arílicos fundidos bicíclicos |
RU2684324C1 (ru) | 2015-08-27 | 2019-04-08 | Пфайзер Инк. | Бициклические конденсированные гетероарильные или арильные соединения в качестве модуляторов IRAK4 |
WO2017037567A1 (en) | 2015-09-03 | 2017-03-09 | Pfizer Inc. | Regulators of frataxin |
CN105481844A (zh) * | 2015-12-08 | 2016-04-13 | 梁彦云 | 一种治疗高血压的药物组合物 |
SI3397631T1 (sl) | 2015-12-29 | 2022-01-31 | Pfizer Inc. | Substituirani 3-azabiciklo(3.1.0)heksani kot zaviralci ketoheksokinaze |
CN106188115A (zh) * | 2016-07-13 | 2016-12-07 | 北京理工大学 | 廉价高效合成2‑二羟硼基‑n‑二甲异噁唑基‑n‑甲氧乙氧甲基苯磺酰胺的新方法 |
SG11201811161YA (en) | 2016-07-14 | 2019-01-30 | Pfizer | Novel pyrimidine carboxamides as inhibitors of vanin-1 enzyme |
KR102513342B1 (ko) | 2016-07-22 | 2023-03-22 | 브리스톨-마이어스 스큅 컴퍼니 | 글루코키나제 활성화제 및 그의 사용 방법 |
AR109179A1 (es) | 2016-08-19 | 2018-11-07 | Pfizer | Inhibidores de diacilglicerol aciltransferasa 2 |
CN117085013A (zh) * | 2016-10-13 | 2023-11-21 | 特拉维尔治疗公司 | 用于治疗肾脏疾病或病症的联苯磺酰胺化合物 |
WO2018162625A1 (en) | 2017-03-09 | 2018-09-13 | Truly Translational Sweden Ab | Prodrugs of sulfasalazine, pharmaceutical compositions thereof and their use in the treatment of autoimmune disease |
DK3630188T3 (da) | 2017-05-31 | 2021-11-15 | Amplio Pharma Ab | Farmaceutisk sammensætning omfattende en kombination af methotrexat og novobiocin og anvendelse af sammensætningen til behandling |
EP3489222A1 (de) | 2017-11-23 | 2019-05-29 | medac Gesellschaft für klinische Spezialpräparate mbH | Sulfasalazinesalze, herstellungsverfahren und verwendungen |
EP3488868B1 (de) | 2017-11-23 | 2023-09-13 | medac Gesellschaft für klinische Spezialpräparate mbH | Pharmazeutische zusammensetzung zur oralen verabreichung enthaltend sulfasalazin oder ein organisches sulfasalazinsalz, herstellungsverfahren und verwendung |
CN111518770B (zh) | 2017-12-19 | 2023-01-06 | 北京吉源生物科技有限公司 | 一种表达glp1和fgf21的干细胞及其用途 |
WO2019133445A1 (en) | 2017-12-28 | 2019-07-04 | Inception Ibd, Inc. | Aminothiazoles as inhibitors of vanin-1 |
WO2020016335A1 (en) | 2018-07-19 | 2020-01-23 | Astrazeneca Ab | Methods of treating hfpef employing dapagliflozin and compositions comprising the same |
AU2019329884B2 (en) | 2018-08-31 | 2022-01-27 | Pfizer Inc. | Combinations for treatment of NASH/NAFLD and related diseases |
KR20210065974A (ko) | 2018-09-26 | 2021-06-04 | 렉시컨 파마슈티컬스 인코퍼레이티드 | N-(1-((2-(디메틸아미노)에틸)아미노)-2-메틸-1-옥소프로판-2-일)-4-(4-(2-메틸-5-((2s,3r,4r,5s,6r)-3,4,5-트리히드록시-6-(메틸티오)테트라히드로-2h-피란-2-일)벤질)페닐)부탄아미드의 결정질 형태 및 그의 합성 방법 |
CN113286587A (zh) | 2018-10-04 | 2021-08-20 | 特拉维尔治疗公司 | 用于治疗iv型胶原病的联苯磺酰胺化合物 |
WO2020102575A1 (en) | 2018-11-16 | 2020-05-22 | Inception Ibd, Inc. | Heterocyclic aminothiazoles and uses thereof |
CN113874019A (zh) | 2019-05-20 | 2021-12-31 | 辉瑞大药厂 | 用于治疗nash/nafld及相关疾病的包含作为glp-1r激动剂的苯并二氧杂环戊烯的组合 |
EP3990452A1 (de) | 2019-06-28 | 2022-05-04 | Pfizer Inc. | 5-(thiophen-2-yl)-1h-tetrazolderivate als bckdk-inhibitoren zur behandlung verschiedener erkrankungen |
TW202115086A (zh) | 2019-06-28 | 2021-04-16 | 美商輝瑞大藥廠 | Bckdk抑制劑 |
TWI771766B (zh) | 2019-10-04 | 2022-07-21 | 美商輝瑞股份有限公司 | 二醯基甘油醯基轉移酶2 抑制劑 |
JP2022058085A (ja) | 2020-02-24 | 2022-04-11 | ファイザー・インク | ジアシルグリセロールアシルトランスフェラーゼ2阻害剤とアセチル-CoAカルボキシラーゼ阻害剤との組合せ |
CN116113635A (zh) | 2020-06-09 | 2023-05-12 | 辉瑞公司 | 作为黑皮质素4受体拮抗剂的螺环化合物及其用途 |
TW202220672A (zh) | 2020-07-27 | 2022-06-01 | 瑞典商阿斯特捷利康公司 | 用達格列淨治療慢性腎臟病之方法 |
WO2022266370A1 (en) | 2021-06-17 | 2022-12-22 | Aria Pharmaceuticals, Inc. | Sparsentan for treating idiopathic pulmonary fibrosis |
WO2023275715A1 (en) | 2021-06-30 | 2023-01-05 | Pfizer Inc. | Metabolites of selective androgen receptor modulators |
WO2023026180A1 (en) | 2021-08-26 | 2023-03-02 | Pfizer Inc. | Amorphous form of (s)-2-(5-((3-ethoxypyridin-2-yl)oxy)pyridin-3-yl)-n-(tetrahydrofuran-3- yl)pyrimidine-5-carboxamide |
CA3229397A1 (en) * | 2021-08-26 | 2023-03-02 | Hualing XIAO | Aromatic ring-containing biological antagonist, and preparation method therefor and use thereof |
CA3235437A1 (en) | 2021-10-21 | 2023-04-27 | Ji Ma | Dual antagonist and use thereof |
AU2022403203A1 (en) | 2021-12-01 | 2024-05-02 | Pfizer Inc. | 3-phenyl-1-benzothiophene-2-carboxylic acid derivatives as branched-chain alpha keto acid dehydrogenase kinase inhibitors for the treatment of diabetes, kidney diseases, nash and heart failure |
WO2023105387A1 (en) | 2021-12-06 | 2023-06-15 | Pfizer Inc. | Melanocortin 4 receptor antagonists and uses thereof |
WO2023144722A1 (en) | 2022-01-26 | 2023-08-03 | Astrazeneca Ab | Dapagliflozin for use in the treatment of prediabetes or reducing the risk of developing type 2 diabetes |
WO2023169456A1 (en) | 2022-03-09 | 2023-09-14 | Gasherbrum Bio , Inc. | Heterocyclic glp-1 agonists |
WO2023198140A1 (en) | 2022-04-14 | 2023-10-19 | Gasherbrum Bio, Inc. | Heterocyclic glp-1 agonists |
WO2023224963A1 (en) * | 2022-05-16 | 2023-11-23 | Aria Pharmaceuticals, Inc. | Dual-acting angiotensin and endothelin receptor antagonists |
WO2024075051A1 (en) | 2022-10-07 | 2024-04-11 | Pfizer Inc. | Hsd17b13 inhibitors and/or degraders |
WO2024084390A1 (en) | 2022-10-18 | 2024-04-25 | Pfizer Inc. | Compounds for the activation of ampk |
WO2024084360A1 (en) | 2022-10-18 | 2024-04-25 | Pfizer Inc. | Patatin-like phospholipase domain-containing protein 3 (pnpla3) modifiers |
Citations (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0490587A1 (de) | 1990-12-07 | 1992-06-17 | Merck & Co. Inc. | Substituierte Pyrazolopyrimidine und Imidezopyridazine als Angiotensin-II-Antagonisten |
EP0518033A1 (de) | 1991-04-16 | 1992-12-16 | Takeda Chemical Industries, Ltd. | Kondensierte heterocyclische Verbindungen, ihre Herstellung und Verwendung |
EP0532410A1 (de) | 1991-09-10 | 1993-03-17 | Sanofi | N-substituierte heterozyklische Derivate als Angiotensin II-Inhibitoren |
US5256658A (en) | 1993-01-15 | 1993-10-26 | Ortho Pharmaceutical Corporation | Angiotensin II inhibitors |
US5326776A (en) | 1992-03-02 | 1994-07-05 | Abbott Laboratories | Angiotensin II receptor antagonists |
DE4300912A1 (de) | 1993-01-15 | 1994-07-21 | Merck Patent Gmbh | Chinazolinderivate |
EP0618207A1 (de) | 1993-03-24 | 1994-10-05 | American Home Products Corporation | Substituierte Pyridopyrimidine als Antihypertensiva |
DE4320432A1 (de) | 1993-06-21 | 1994-12-22 | Bayer Ag | Substituierte Mono- und Bipyridylmethylderivate |
GB2280438A (en) | 1993-07-30 | 1995-02-01 | Kotobuki Seiyaku Co Ltd | Carboxymethylidenecycloheptimidazole derivatives method of manufacturing the same and therapeutic agents containing these compounds |
WO1995012598A1 (en) | 1993-11-02 | 1995-05-11 | Merck & Co., Inc. | Benzo-fused macrocycles promote release of growth hormone |
EP0708103A1 (de) | 1994-10-19 | 1996-04-24 | Sanofi | Verfahren zur Herstellung eines Tetrazolderivates in zwei kristallinen Formen und eine neue Kristallform dieses Derivates |
US5674879A (en) | 1993-09-24 | 1997-10-07 | G.D. Searle & Co. | Compositions including and methods of using conformationally restricted angiotensin II antagonist |
WO1997040040A1 (en) | 1996-04-19 | 1997-10-30 | Istituto Luso Farmaco D'italia S.P.A. | N-3 substituted pyrimidin-4-ones with aii antagonistic activity |
JPH09291078A (ja) | 1996-04-25 | 1997-11-11 | Kyorin Pharmaceut Co Ltd | オルトメトキシフェニルピペラジニルアルコキシアリール基を有する新規イミダゾール誘導体及びその製造法 |
Family Cites Families (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4880804A (en) * | 1988-01-07 | 1989-11-14 | E. I. Du Pont De Nemours And Company | Angiotensin II receptor blocking benzimidazoles |
IL94390A (en) * | 1989-05-30 | 1996-03-31 | Merck & Co Inc | The 6-membered trans-nitrogen-containing heterocycles are compressed with imidazo and pharmaceutical preparations containing them |
US5240928A (en) * | 1989-07-03 | 1993-08-31 | Merck & Co., Inc. | Substituted quinazolinones as angiotensin II antagonists |
CA2020073A1 (en) * | 1989-07-03 | 1991-01-04 | Eric E. Allen | Substituted quinazolinones as angiotensin ii antagonists |
EP0515535A4 (en) | 1990-02-13 | 1996-01-17 | Merck & Co Inc | Angiotensin ii antagonists incorporating a substituted benzyl element |
EP0443983B1 (de) * | 1990-02-19 | 1996-02-28 | Ciba-Geigy Ag | Acylverbindungen |
SU1724657A1 (ru) | 1990-02-26 | 1992-04-07 | Научно-Производственный Кооператив "Охрана Природы" | Способ приготовлени сапропелевого удобрени |
US5250548A (en) * | 1990-09-10 | 1993-10-05 | Abbott Laboratories | Angiotensin II receptor antagonists |
IE912956A1 (en) * | 1990-09-10 | 1992-03-11 | Abbott Lab | Angiotensin ii receptor antagonists |
CA2079982A1 (en) * | 1991-10-07 | 1993-04-08 | Stephen E. De Laszlo | Substituted pyrazino (2,3-d)-pyrimidinones as angiotensin ii antagonists |
US5674883A (en) * | 1992-02-07 | 1997-10-07 | Roussel Uclaf | Derivatives of pyridone, their preparation process, the new intermediates obtained, their use as medicaments and the pharmaceutical compositions containing them |
GB2264710A (en) * | 1992-03-04 | 1993-09-08 | Merck & Co Inc | Quinoline and azaquinoline angiotensin ii antagonists incorporating a substituted biphenyl element |
DE4208304A1 (de) * | 1992-03-16 | 1993-09-23 | Merck Patent Gmbh | 2-oxochinolinderivate |
US5514696A (en) * | 1992-05-06 | 1996-05-07 | Bristol-Myers Squibb Co. | Phenyl sulfonamide endothelin antagonists |
RU2041866C1 (ru) | 1994-01-20 | 1995-08-20 | Акционерное предприятие "Сапропель-Неро" | Способ добычи и получения сапропелевого удобрения |
US5612359A (en) * | 1994-08-26 | 1997-03-18 | Bristol-Myers Squibb Company | Substituted biphenyl isoxazole sulfonamides |
IL116916A (en) * | 1995-02-06 | 2000-09-28 | Bristol Myers Squibb Co | Substituted biphenyl sulfonamide derivatives and pharmaceutical compositions containing the same |
US5760038A (en) * | 1995-02-06 | 1998-06-02 | Bristol-Myers Squibb Company | Substituted biphenyl sulfonamide endothelin antagonists |
KR100359396B1 (ko) * | 1995-04-04 | 2003-03-15 | 텍사스 바이오테크놀로지 코포레이션 | 엔도텔린의활성을조절하는티에닐-,푸릴-및피롤릴설폰아미드및이의유도체 |
GB9512697D0 (en) * | 1995-06-22 | 1995-08-23 | Zeneca Ltd | Heterocyclic compounds |
US5846990A (en) * | 1995-07-24 | 1998-12-08 | Bristol-Myers Squibb Co. | Substituted biphenyl isoxazole sulfonamides |
HUP0002351A3 (en) | 1996-02-20 | 2001-10-29 | Bristol Myers Squibb Co | Methods for the preparation of biphenyl isoxazole sulfonamides, intermediates and process for preparing them |
AU2074297A (en) * | 1996-03-12 | 1997-10-01 | Bristol-Myers Squibb Company | Substituted biphenyl isoxazole sulfonamides |
US5939446A (en) * | 1996-04-09 | 1999-08-17 | Bristol-Myers Squibb Co. | Heteroaryl substituted phenyl isoxazole sulfonamide endothelin antagonists |
TW536540B (en) | 1997-01-30 | 2003-06-11 | Bristol Myers Squibb Co | Endothelin antagonists: N-[[2'-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-4-(2-oxazolyl)[1,1'-biphenyl]-2-yl]methyl]-N,3,3-trimethylbutanamide and N-(4,5-dimethyl-3-isoxazolyl)-2'-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl]-4'-(2-oxazolyl)[1,1'-biphe |
US5846985A (en) * | 1997-03-05 | 1998-12-08 | Bristol-Myers Squibb Co. | Substituted biphenyl isoxazole sulfonamides |
CA2336714A1 (en) * | 1998-07-06 | 2000-01-13 | Bristol-Myers Squibb Company | Biphenyl sulfonamides as dual angiotensin endothelin receptor antagonists |
-
1999
- 1999-07-01 CA CA002336714A patent/CA2336714A1/en not_active Abandoned
- 1999-07-01 GE GEAP19995709A patent/GEP20033114B/en unknown
- 1999-07-01 CZ CZ200172A patent/CZ200172A3/cs unknown
- 1999-07-01 EP EP99935406A patent/EP1094816B1/de not_active Expired - Lifetime
- 1999-07-01 EE EEP200100006A patent/EE200100006A/xx unknown
- 1999-07-01 PL PL346443A patent/PL201048B1/pl not_active IP Right Cessation
- 1999-07-01 DE DE69940063T patent/DE69940063D1/de not_active Expired - Lifetime
- 1999-07-01 CN CNB99808252XA patent/CN1149196C/zh not_active Expired - Lifetime
- 1999-07-01 WO PCT/US1999/015063 patent/WO2000001389A1/en active Application Filing
- 1999-07-01 NZ NZ508118A patent/NZ508118A/en unknown
- 1999-07-01 PL PL384282A patent/PL203771B1/pl not_active IP Right Cessation
- 1999-07-01 PT PT99935406T patent/PT1094816E/pt unknown
- 1999-07-01 EP EP08006531A patent/EP2002837A1/de not_active Withdrawn
- 1999-07-01 SK SK1882-2000A patent/SK18822000A3/sk unknown
- 1999-07-01 BR BR9911621-9A patent/BR9911621A/pt not_active IP Right Cessation
- 1999-07-01 ID IDW20010015A patent/ID26984A/id unknown
- 1999-07-01 AT AT99935406T patent/ATE416772T1/de not_active IP Right Cessation
- 1999-07-01 DK DK99935406T patent/DK1094816T3/da active
- 1999-07-01 KR KR1020017000186A patent/KR20010083092A/ko not_active Application Discontinuation
- 1999-07-01 HU HU0104634A patent/HUP0104634A3/hu unknown
- 1999-07-01 TR TR2001/00149T patent/TR200100149T2/xx unknown
- 1999-07-01 AU AU50888/99A patent/AU767456B2/en not_active Ceased
- 1999-07-01 RU RU2001103044/04A patent/RU2001103044A/ru not_active Application Discontinuation
- 1999-07-01 JP JP2000557835A patent/JP2002519380A/ja active Pending
- 1999-07-01 IL IL14062299A patent/IL140622A0/xx unknown
- 1999-07-01 ES ES99935406T patent/ES2318899T3/es not_active Expired - Lifetime
-
2000
- 2000-11-20 ZA ZA200006772A patent/ZA200006772B/en unknown
- 2000-12-22 LT LT2000123A patent/LT4854B/lt not_active IP Right Cessation
-
2001
- 2001-01-05 NO NO20010062A patent/NO20010062L/no not_active Application Discontinuation
- 2001-01-16 LT LT2001004A patent/LT4864B/lt not_active IP Right Cessation
- 2001-01-31 BG BG105205A patent/BG65404B1/bg unknown
- 2001-02-05 LV LV010017A patent/LV12639B/xx unknown
-
2010
- 2010-04-28 JP JP2010104028A patent/JP2010209096A/ja active Pending
Patent Citations (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0490587A1 (de) | 1990-12-07 | 1992-06-17 | Merck & Co. Inc. | Substituierte Pyrazolopyrimidine und Imidezopyridazine als Angiotensin-II-Antagonisten |
EP0518033A1 (de) | 1991-04-16 | 1992-12-16 | Takeda Chemical Industries, Ltd. | Kondensierte heterocyclische Verbindungen, ihre Herstellung und Verwendung |
EP0532410A1 (de) | 1991-09-10 | 1993-03-17 | Sanofi | N-substituierte heterozyklische Derivate als Angiotensin II-Inhibitoren |
US5326776A (en) | 1992-03-02 | 1994-07-05 | Abbott Laboratories | Angiotensin II receptor antagonists |
US5256658A (en) | 1993-01-15 | 1993-10-26 | Ortho Pharmaceutical Corporation | Angiotensin II inhibitors |
DE4300912A1 (de) | 1993-01-15 | 1994-07-21 | Merck Patent Gmbh | Chinazolinderivate |
EP0618207A1 (de) | 1993-03-24 | 1994-10-05 | American Home Products Corporation | Substituierte Pyridopyrimidine als Antihypertensiva |
DE4320432A1 (de) | 1993-06-21 | 1994-12-22 | Bayer Ag | Substituierte Mono- und Bipyridylmethylderivate |
GB2280438A (en) | 1993-07-30 | 1995-02-01 | Kotobuki Seiyaku Co Ltd | Carboxymethylidenecycloheptimidazole derivatives method of manufacturing the same and therapeutic agents containing these compounds |
US5674879A (en) | 1993-09-24 | 1997-10-07 | G.D. Searle & Co. | Compositions including and methods of using conformationally restricted angiotensin II antagonist |
WO1995012598A1 (en) | 1993-11-02 | 1995-05-11 | Merck & Co., Inc. | Benzo-fused macrocycles promote release of growth hormone |
EP0708103A1 (de) | 1994-10-19 | 1996-04-24 | Sanofi | Verfahren zur Herstellung eines Tetrazolderivates in zwei kristallinen Formen und eine neue Kristallform dieses Derivates |
WO1997040040A1 (en) | 1996-04-19 | 1997-10-30 | Istituto Luso Farmaco D'italia S.P.A. | N-3 substituted pyrimidin-4-ones with aii antagonistic activity |
JPH09291078A (ja) | 1996-04-25 | 1997-11-11 | Kyorin Pharmaceut Co Ltd | オルトメトキシフェニルピペラジニルアルコキシアリール基を有する新規イミダゾール誘導体及びその製造法 |
Non-Patent Citations (2)
Title |
---|
RED. T. W. GREENE, P. G. M. WUTS: "Protecting Groups in Chemical Synthesis (2nd ed.)", pages: 175 - 276 |
ZHANG HONG-YUE, YU JIAN-QIU, THOMAS C. BRUICE: "Synthesis of a spheroidal bis-porphyrin: a ligand designed to accept two catalytic metal ions in an isolated environment", TETRAHEDRON, 1994, pages 11339 - 11362 |
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