CA2430808A1 - Cycloalkylfused [g]-indole compounds as spla2-inhibitors in the treatment of inflammatory diseases - Google Patents
Cycloalkylfused [g]-indole compounds as spla2-inhibitors in the treatment of inflammatory diseases Download PDFInfo
- Publication number
- CA2430808A1 CA2430808A1 CA002430808A CA2430808A CA2430808A1 CA 2430808 A1 CA2430808 A1 CA 2430808A1 CA 002430808 A CA002430808 A CA 002430808A CA 2430808 A CA2430808 A CA 2430808A CA 2430808 A1 CA2430808 A1 CA 2430808A1
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- Prior art keywords
- group
- amino
- hydrogen
- compound
- acid
- Prior art date
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- 238000011282 treatment Methods 0.000 title claims abstract description 17
- 208000027866 inflammatory disease Diseases 0.000 title claims abstract description 15
- 239000003112 inhibitor Substances 0.000 title claims description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 178
- 102000005473 Secretory Phospholipases A2 Human genes 0.000 claims abstract description 23
- 108010031873 Secretory Phospholipases A2 Proteins 0.000 claims abstract description 23
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 10
- 239000000194 fatty acid Substances 0.000 claims abstract description 10
- 229930195729 fatty acid Natural products 0.000 claims abstract description 10
- 150000004665 fatty acids Chemical class 0.000 claims abstract description 10
- 230000001404 mediated effect Effects 0.000 claims abstract description 9
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 6
- 239000000203 mixture Substances 0.000 claims description 163
- -1 indole compound Chemical class 0.000 claims description 114
- 239000002253 acid Substances 0.000 claims description 94
- 229910052739 hydrogen Inorganic materials 0.000 claims description 78
- 239000001257 hydrogen Substances 0.000 claims description 69
- 125000005647 linker group Chemical group 0.000 claims description 61
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 57
- 150000002431 hydrogen Chemical class 0.000 claims description 36
- 125000001424 substituent group Chemical group 0.000 claims description 36
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 34
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 34
- 125000003118 aryl group Chemical group 0.000 claims description 31
- 238000000034 method Methods 0.000 claims description 31
- 125000004442 acylamino group Chemical group 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
- 229910052760 oxygen Inorganic materials 0.000 claims description 25
- 229910052717 sulfur Inorganic materials 0.000 claims description 25
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 24
- 150000001413 amino acids Chemical class 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 22
- 239000001301 oxygen Substances 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 20
- 125000003368 amide group Chemical group 0.000 claims description 20
- 125000004429 atom Chemical group 0.000 claims description 20
- 239000011593 sulfur Substances 0.000 claims description 20
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 20
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 19
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 19
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 19
- 230000002452 interceptive effect Effects 0.000 claims description 18
- 239000000651 prodrug Substances 0.000 claims description 18
- 229940002612 prodrug Drugs 0.000 claims description 18
- 230000002378 acidificating effect Effects 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- 150000001408 amides Chemical group 0.000 claims description 14
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 125000000539 amino acid group Chemical group 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 9
- 239000012453 solvate Substances 0.000 claims description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
- 125000003277 amino group Chemical group 0.000 claims description 8
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 125000004104 aryloxy group Chemical group 0.000 claims description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 5
- RNQBSGBIXRVGAB-UHFFFAOYSA-N methyl 2-[(1-benzyl-2-methyl-3-oxamoyl-7,8-dihydro-6h-cyclopenta[g]indol-4-yl)oxy]acetate Chemical compound CC1=C(C(=O)C(N)=O)C=2C(OCC(=O)OC)=CC=3CCCC=3C=2N1CC1=CC=CC=C1 RNQBSGBIXRVGAB-UHFFFAOYSA-N 0.000 claims description 5
- XJOYKEUYMKOUFJ-UHFFFAOYSA-N methyl 2-[[1-[(3-fluorophenyl)methyl]-2-methyl-3-oxamoyl-7,8-dihydro-6h-cyclopenta[g]indol-4-yl]oxy]acetate Chemical compound CC1=C(C(=O)C(N)=O)C=2C(OCC(=O)OC)=CC=3CCCC=3C=2N1CC1=CC=CC(F)=C1 XJOYKEUYMKOUFJ-UHFFFAOYSA-N 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- VCUWZUBFYRWFSA-UHFFFAOYSA-N 2-[(1-benzyl-2-ethyl-3-oxamoyl-7,8-dihydro-6h-cyclopenta[g]indol-4-yl)oxy]acetic acid Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)C=C3CCCC3=C2N1CC1=CC=CC=C1 VCUWZUBFYRWFSA-UHFFFAOYSA-N 0.000 claims description 4
- GPJLXZYUPFLUAV-UHFFFAOYSA-N 2-[(1-benzyl-2-methyl-3-oxamoyl-7,8-dihydro-6h-cyclopenta[g]indol-4-yl)oxy]acetic acid Chemical compound CC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)C=C3CCCC3=C2N1CC1=CC=CC=C1 GPJLXZYUPFLUAV-UHFFFAOYSA-N 0.000 claims description 4
- SACJSCPRTMXKND-UHFFFAOYSA-N 2-[4-[2-(benzenesulfonamido)-2-oxoethoxy]-1-benzyl-2-methyl-7,8-dihydro-6h-cyclopenta[g]indol-3-yl]-2-oxoacetamide Chemical compound C1=C2CCCC2=C2N(CC=3C=CC=CC=3)C(C)=C(C(=O)C(N)=O)C2=C1OCC(=O)NS(=O)(=O)C1=CC=CC=C1 SACJSCPRTMXKND-UHFFFAOYSA-N 0.000 claims description 4
- 125000003358 C2-C20 alkenyl group Chemical group 0.000 claims description 4
- 239000004305 biphenyl Substances 0.000 claims description 4
- 235000010290 biphenyl Nutrition 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- LBZKCAJYHMFIHZ-UHFFFAOYSA-N methyl 2-[(1-benzyl-2-ethyl-3-oxamoyl-7,8-dihydro-6h-cyclopenta[g]indol-4-yl)oxy]acetate Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(=O)OC)C=C3CCCC3=C2N1CC1=CC=CC=C1 LBZKCAJYHMFIHZ-UHFFFAOYSA-N 0.000 claims description 4
- KPHTURWORNAMCY-UHFFFAOYSA-N methyl 2-[[1-[(2-bromophenyl)methyl]-2-methyl-3-oxamoyl-7,8-dihydro-6h-cyclopenta[g]indol-4-yl]oxy]acetate Chemical compound CC1=C(C(=O)C(N)=O)C=2C(OCC(=O)OC)=CC=3CCCC=3C=2N1CC1=CC=CC=C1Br KPHTURWORNAMCY-UHFFFAOYSA-N 0.000 claims description 4
- SFRHPDAELMPMGD-UHFFFAOYSA-N methyl 2-[[1-[(4-fluorophenyl)methyl]-2-methyl-3-oxamoyl-7,8-dihydro-6h-cyclopenta[g]indol-4-yl]oxy]acetate Chemical compound CC1=C(C(=O)C(N)=O)C=2C(OCC(=O)OC)=CC=3CCCC=3C=2N1CC1=CC=C(F)C=C1 SFRHPDAELMPMGD-UHFFFAOYSA-N 0.000 claims description 4
- 125000005425 toluyl group Chemical group 0.000 claims description 4
- 125000002256 xylenyl group Chemical group C1(C(C=CC=C1)C)(C)* 0.000 claims description 4
- 125000006755 (C2-C20) alkyl group Chemical group 0.000 claims description 3
- QDOYKUBOULWYOE-UHFFFAOYSA-N 2-[[1-[(2-fluorophenyl)methyl]-2-methyl-3-oxamoyl-7,8-dihydro-6h-cyclopenta[g]indol-4-yl]oxy]acetic acid Chemical compound CC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)C=C3CCCC3=C2N1CC1=CC=CC=C1F QDOYKUBOULWYOE-UHFFFAOYSA-N 0.000 claims description 3
- NECXUEJKKBTQOR-UHFFFAOYSA-N 2-[[1-[(3-fluorophenyl)methyl]-2-methyl-3-oxamoyl-7,8-dihydro-6h-cyclopenta[g]indol-4-yl]oxy]acetic acid;hydrate Chemical compound O.CC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)C=C3CCCC3=C2N1CC1=CC=CC(F)=C1 NECXUEJKKBTQOR-UHFFFAOYSA-N 0.000 claims description 3
- KKLIXGKAGOYMQS-UHFFFAOYSA-N 2-[[2-methyl-3-oxamoyl-1-[(2-phenylphenyl)methyl]-7,8-dihydro-6h-cyclopenta[g]indol-4-yl]oxy]acetic acid Chemical compound CC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)C=C3CCCC3=C2N1CC1=CC=CC=C1C1=CC=CC=C1 KKLIXGKAGOYMQS-UHFFFAOYSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 3
- CKIAPLBTQDVUAK-UHFFFAOYSA-N methyl 2-[[2-methyl-3-oxamoyl-1-[(2-phenylphenyl)methyl]-7,8-dihydro-6h-cyclopenta[g]indol-4-yl]oxy]acetate Chemical compound CC1=C(C(=O)C(N)=O)C=2C(OCC(=O)OC)=CC=3CCCC=3C=2N1CC1=CC=CC=C1C1=CC=CC=C1 CKIAPLBTQDVUAK-UHFFFAOYSA-N 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
- XFWYGPJGSADHTQ-UHFFFAOYSA-N 2-[(1-benzyl-2-ethyl-3-oxamoyl-6,7,8,9-tetrahydrobenzo[g]indol-4-yl)oxy]acetic acid Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)C=C3CCCCC3=C2N1CC1=CC=CC=C1 XFWYGPJGSADHTQ-UHFFFAOYSA-N 0.000 claims description 2
- ZRGYYOLGPYAKHM-UHFFFAOYSA-N 2-[[1-[(2-bromophenyl)methyl]-2-methyl-3-oxamoyl-7,8-dihydro-6h-cyclopenta[g]indol-4-yl]oxy]acetic acid Chemical compound CC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)C=C3CCCC3=C2N1CC1=CC=CC=C1Br ZRGYYOLGPYAKHM-UHFFFAOYSA-N 0.000 claims description 2
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 2
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 2
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 2
- 125000000033 alkoxyamino group Chemical group 0.000 claims description 2
- 125000004694 alkoxyaminocarbonyl group Chemical group 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- 125000004691 alkyl thio carbonyl group Chemical group 0.000 claims description 2
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 2
- 125000004441 haloalkylsulfonyl group Chemical group 0.000 claims description 2
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 2
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- 150000003555 thioacetals Chemical class 0.000 claims description 2
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 11
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 3
- 229910006069 SO3H Inorganic materials 0.000 claims 2
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims 1
- 125000006553 (C3-C8) cycloalkenyl group Chemical group 0.000 claims 1
- PXKIHESMECOGFM-UHFFFAOYSA-N 2-[(1-benzyl-2-methyl-3-oxamoyl-6,7,8,9-tetrahydrobenzo[g]indol-4-yl)oxy]acetic acid Chemical compound CC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)C=C3CCCCC3=C2N1CC1=CC=CC=C1 PXKIHESMECOGFM-UHFFFAOYSA-N 0.000 claims 1
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims 1
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims 1
- KPXWDTTXZCZOHS-UHFFFAOYSA-N methyl 2-[(1-benzyl-2-ethyl-3-oxamoyl-6,7,8,9-tetrahydrobenzo[g]indol-4-yl)oxy]acetate Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(=O)OC)C=C3CCCCC3=C2N1CC1=CC=CC=C1 KPXWDTTXZCZOHS-UHFFFAOYSA-N 0.000 claims 1
- JQGNJUHTHIGZBR-UHFFFAOYSA-N methyl 2-[(1-benzyl-2-methyl-3-oxamoyl-6,7,8,9-tetrahydrobenzo[g]indol-4-yl)oxy]acetate Chemical compound CC1=C(C(=O)C(N)=O)C=2C(OCC(=O)OC)=CC=3CCCCC=3C=2N1CC1=CC=CC=C1 JQGNJUHTHIGZBR-UHFFFAOYSA-N 0.000 claims 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
- 230000001575 pathological effect Effects 0.000 claims 1
- 150000002475 indoles Chemical class 0.000 abstract description 26
- 206010040070 Septic Shock Diseases 0.000 abstract description 3
- 230000036303 septic shock Effects 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 198
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 129
- 239000000243 solution Substances 0.000 description 117
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 109
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 105
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 90
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 86
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical group CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 79
- 229940073584 methylene chloride Drugs 0.000 description 65
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 60
- 238000002360 preparation method Methods 0.000 description 59
- 239000007787 solid Substances 0.000 description 56
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 49
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 48
- 101150041968 CDC13 gene Proteins 0.000 description 46
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 46
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 43
- 235000019439 ethyl acetate Nutrition 0.000 description 43
- 238000005160 1H NMR spectroscopy Methods 0.000 description 40
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 40
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 40
- 238000006243 chemical reaction Methods 0.000 description 39
- 239000000741 silica gel Substances 0.000 description 39
- 229910002027 silica gel Inorganic materials 0.000 description 39
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 34
- 125000000217 alkyl group Chemical group 0.000 description 33
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 33
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 31
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 27
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 25
- 239000004480 active ingredient Substances 0.000 description 25
- 238000004587 chromatography analysis Methods 0.000 description 24
- 239000000706 filtrate Substances 0.000 description 24
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 23
- 239000000047 product Substances 0.000 description 23
- 229910000104 sodium hydride Inorganic materials 0.000 description 23
- 229910052938 sodium sulfate Inorganic materials 0.000 description 23
- 235000011152 sodium sulphate Nutrition 0.000 description 23
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 22
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 22
- 238000003828 vacuum filtration Methods 0.000 description 22
- 229910000024 caesium carbonate Inorganic materials 0.000 description 21
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 21
- 238000003756 stirring Methods 0.000 description 20
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 19
- 150000002148 esters Chemical class 0.000 description 19
- 239000002244 precipitate Substances 0.000 description 19
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 18
- 229920006395 saturated elastomer Polymers 0.000 description 18
- 235000001014 amino acid Nutrition 0.000 description 17
- 229940024606 amino acid Drugs 0.000 description 17
- 239000012044 organic layer Substances 0.000 description 17
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- 239000000725 suspension Substances 0.000 description 16
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical group CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 15
- 238000005481 NMR spectroscopy Methods 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 14
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 14
- 238000009472 formulation Methods 0.000 description 14
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 14
- 150000003254 radicals Chemical class 0.000 description 14
- 239000012279 sodium borohydride Substances 0.000 description 14
- 229910000033 sodium borohydride Inorganic materials 0.000 description 14
- 229910015845 BBr3 Inorganic materials 0.000 description 13
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 13
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- SSUCKKNRCOFUPT-UHFFFAOYSA-N o-[tert-butyl(dimethyl)silyl]hydroxylamine Chemical compound CC(C)(C)[Si](C)(C)ON SSUCKKNRCOFUPT-UHFFFAOYSA-N 0.000 description 1
- 239000012053 oil suspension Substances 0.000 description 1
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- 235000019161 pantothenic acid Nutrition 0.000 description 1
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- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
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- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
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- 201000006292 polyarteritis nodosa Diseases 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
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- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
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- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
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- 208000009169 relapsing polychondritis Diseases 0.000 description 1
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- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- SVOOVMQUISJERI-UHFFFAOYSA-K rhodium(3+);triacetate Chemical class [Rh+3].CC([O-])=O.CC([O-])=O.CC([O-])=O SVOOVMQUISJERI-UHFFFAOYSA-K 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
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- 239000000523 sample Substances 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000012056 semi-solid material Substances 0.000 description 1
- 201000001223 septic arthritis Diseases 0.000 description 1
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- 208000007056 sickle cell anemia Diseases 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
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- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 230000003156 vasculitic effect Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/58—[b]- or [c]-condensed
- C07D209/70—[b]- or [c]-condensed containing carbocyclic rings other than six-membered
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/58—[b]- or [c]-condensed
- C07D209/60—Naphtho [b] pyrroles; Hydrogenated naphtho [b] pyrroles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Rheumatology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Otolaryngology (AREA)
- Pain & Pain Management (AREA)
- Dermatology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US25639700P | 2000-12-18 | 2000-12-18 | |
| US60/256,397 | 2000-12-18 | ||
| PCT/US2001/043187 WO2002050030A2 (en) | 2000-12-18 | 2001-12-06 | Cycloalkylfused [g]-indole compounds as spla2-inhibitors in the treatment of inflammatory diseases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2430808A1 true CA2430808A1 (en) | 2002-06-27 |
Family
ID=22972097
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002430808A Abandoned CA2430808A1 (en) | 2000-12-18 | 2001-12-06 | Cycloalkylfused [g]-indole compounds as spla2-inhibitors in the treatment of inflammatory diseases |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US6974831B2 (OSRAM) |
| EP (1) | EP1349834A2 (OSRAM) |
| JP (1) | JP2004518658A (OSRAM) |
| AU (1) | AU2002233928A1 (OSRAM) |
| CA (1) | CA2430808A1 (OSRAM) |
| WO (1) | WO2002050030A2 (OSRAM) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005107767A2 (en) * | 2004-05-03 | 2005-11-17 | Ilypsa, Inc. | Modulation of lysophosphatidylcholine and treatment of diet-induced conditions |
| US20110104109A1 (en) * | 2005-07-13 | 2011-05-05 | Frank Bennett | Tetracyclic indole derivatives and their use for treating or preventing viral infections |
| AU2006311765A1 (en) * | 2005-11-03 | 2007-05-18 | Ilypsa, Inc. | Phospholipase inhibitors, including multi-valent phospholipase inhibitors, and use thereof, including as lumen-localized phospholipase inhibitors |
| JP2009515837A (ja) * | 2005-11-03 | 2009-04-16 | イリプサ， インコーポレイテッド | Ｃ４−酸性置換基を有するインドール化合物およびホスホリパーゼａ２インヒビターとしてのその使用 |
| WO2007056281A2 (en) * | 2005-11-03 | 2007-05-18 | Ilypsa, Inc. | Multivalent indole compounds and use thereof as phospholipase-a2 inhibitors |
| US20090239896A1 (en) * | 2005-11-03 | 2009-09-24 | Han-Ting Chang | Azaindole compounds and use thereof as phospholipase-a2 inhibitors |
| US20090306171A1 (en) * | 2005-11-03 | 2009-12-10 | Han-Ting Chang | Indole compounds having c4-amide substituents and use thereof as phospholipase-a2 inhibitors |
| WO2008082488A1 (en) * | 2006-12-22 | 2008-07-10 | Schering Corporation | 4, 5-ring annulated indole derivatives for treating or preventing of hcv and related viral infections |
| WO2008082484A1 (en) | 2006-12-22 | 2008-07-10 | Schering Corporation | 4,5-ring annulated indole derivatives for treating or preventing of hcv and related viral infections |
| ATE543808T1 (de) | 2006-12-22 | 2012-02-15 | Schering Corp | 5,6-ring-annelierte indolderivate und ihre verwendung |
| ATE541845T1 (de) * | 2007-08-29 | 2012-02-15 | Schering Corp | 2,3-substituierte azaindolderivate zur behandlung von virusinfektionen |
| JP5272008B2 (ja) * | 2007-08-29 | 2013-08-28 | メルク・シャープ・アンド・ドーム・コーポレーション | 置換インドール誘導体およびその使用の方法 |
| PE20090995A1 (es) * | 2007-08-29 | 2009-08-03 | Schering Corp | Derivados indolicos 2,3-sustituidos como inhibidores del virus de la hepatitis c (vhc) |
| JP5416708B2 (ja) * | 2007-11-16 | 2014-02-12 | メルク・シャープ・アンド・ドーム・コーポレーション | ３−アミノスルホニル置換インドール誘導体およびそれらの使用方法 |
| JP5249344B2 (ja) * | 2007-11-16 | 2013-07-31 | メルク・シャープ・アンド・ドーム・コーポレーション | ヘテロ環の３位が置換されたインドール誘導体およびその使用 |
| MX2010013630A (es) * | 2008-06-13 | 2010-12-21 | Schering Corp | Derivados triciclicos de indol y metodos de uso de los mismos. |
| NZ720946A (en) | 2009-04-29 | 2017-09-29 | Amarin Pharmaceuticals Ie Ltd | Pharmaceutical compositions comprising epa and a cardiovascular agent and methods of using the same |
| CN117120442A (zh) * | 2021-01-26 | 2023-11-24 | 薛定谔公司 | 用于治疗癌症、自身免疫性病症和炎性病症的三环化合物 |
| TW202417445A (zh) * | 2022-07-22 | 2024-05-01 | 美商薛定諤公司 | 環狀化合物及其使用方法 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE195935T1 (de) | 1993-03-25 | 2000-09-15 | Upjohn Co | Formyl- oder cyano- substituierte indolderivate mit dopaminergischer wirkung |
| IL109309A (en) * | 1993-04-16 | 2000-06-29 | Lilly Co Eli | 1-H-indole-3-acetic acid hydrazide SPLA2 inhibitors and pharmaceutical compositions containing them |
| IL109311A0 (en) | 1993-04-16 | 1994-07-31 | Lilly Co Eli | 1H-indole-3-acetamide sPla2 inhibitors |
| WO2000010568A1 (en) * | 1998-08-24 | 2000-03-02 | Draheim Susan E | Methods and compositions for treating periodontal disease with an inhibitor of secretory phospholipase a¿2? |
| US6140327A (en) * | 1999-05-12 | 2000-10-31 | Eli Lilly And Company | Morpholino-n-ethyl ester derivative of an indole sPLA2 inhibitor |
| US6831095B1 (en) * | 1999-09-20 | 2004-12-14 | Eli Lilly And Company | Hydroxyfunctional amide 1h-indole derivatives active as sPLA2 inhibitors |
-
2001
- 2001-12-06 US US10/450,741 patent/US6974831B2/en not_active Expired - Fee Related
- 2001-12-06 JP JP2002551527A patent/JP2004518658A/ja active Pending
- 2001-12-06 AU AU2002233928A patent/AU2002233928A1/en not_active Abandoned
- 2001-12-06 CA CA002430808A patent/CA2430808A1/en not_active Abandoned
- 2001-12-06 WO PCT/US2001/043187 patent/WO2002050030A2/en not_active Ceased
- 2001-12-06 EP EP01984924A patent/EP1349834A2/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| WO2002050030A2 (en) | 2002-06-27 |
| US20040077704A1 (en) | 2004-04-22 |
| AU2002233928A1 (en) | 2002-07-01 |
| WO2002050030A3 (en) | 2002-09-12 |
| US6974831B2 (en) | 2005-12-13 |
| JP2004518658A (ja) | 2004-06-24 |
| WO2002050030A8 (en) | 2003-11-13 |
| EP1349834A2 (en) | 2003-10-08 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |