ZA200400849B - Combination therapy for the treatment of cancer. - Google Patents
Combination therapy for the treatment of cancer. Download PDFInfo
- Publication number
- ZA200400849B ZA200400849B ZA200400849A ZA200400849A ZA200400849B ZA 200400849 B ZA200400849 B ZA 200400849B ZA 200400849 A ZA200400849 A ZA 200400849A ZA 200400849 A ZA200400849 A ZA 200400849A ZA 200400849 B ZA200400849 B ZA 200400849B
- Authority
- ZA
- South Africa
- Prior art keywords
- group
- hydrogen
- formula
- alkyl
- cyclooxygenase
- Prior art date
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- 238000011282 treatment Methods 0.000 title claims description 108
- 206010028980 Neoplasm Diseases 0.000 title claims description 70
- 201000011510 cancer Diseases 0.000 title description 14
- 238000002648 combination therapy Methods 0.000 title description 8
- -1 piperazin-1-ylmethyl Chemical group 0.000 claims description 256
- 229910052739 hydrogen Inorganic materials 0.000 claims description 233
- 239000001257 hydrogen Substances 0.000 claims description 230
- 125000000217 alkyl group Chemical group 0.000 claims description 217
- 238000000034 method Methods 0.000 claims description 135
- 150000001875 compounds Chemical class 0.000 claims description 114
- 125000003118 aryl group Chemical group 0.000 claims description 102
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 99
- 239000000203 mixture Substances 0.000 claims description 94
- 150000003839 salts Chemical class 0.000 claims description 90
- 239000000126 substance Substances 0.000 claims description 88
- 125000003545 alkoxy group Chemical group 0.000 claims description 84
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 82
- 230000002265 prevention Effects 0.000 claims description 82
- 108010037462 Cyclooxygenase 2 Proteins 0.000 claims description 80
- 229940124639 Selective inhibitor Drugs 0.000 claims description 80
- 229940043355 kinase inhibitor Drugs 0.000 claims description 78
- 239000003909 protein kinase inhibitor Substances 0.000 claims description 74
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 73
- 125000005843 halogen group Chemical group 0.000 claims description 66
- 125000001072 heteroaryl group Chemical group 0.000 claims description 65
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 39
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 37
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 34
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 29
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 28
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 24
- 241000124008 Mammalia Species 0.000 claims description 21
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 17
- 125000001188 haloalkyl group Chemical group 0.000 claims description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims description 16
- 125000004104 aryloxy group Chemical group 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 150000003254 radicals Chemical group 0.000 claims description 14
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 13
- 125000006260 ethylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])C([H])([H])[H] 0.000 claims description 12
- 125000001153 fluoro group Chemical group F* 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 125000004953 trihalomethyl group Chemical group 0.000 claims description 12
- 125000001246 bromo group Chemical group Br* 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 11
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 claims description 11
- 229940122204 Cyclooxygenase inhibitor Drugs 0.000 claims description 10
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 125000002252 acyl group Chemical group 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 125000003282 alkyl amino group Chemical group 0.000 claims description 8
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 8
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 8
- 125000006263 dimethyl aminosulfonyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])S(*)(=O)=O 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims description 7
- 125000005099 aryl alkyl carbonyl group Chemical group 0.000 claims description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 7
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- 239000011593 sulfur Substances 0.000 claims description 7
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 125000005191 hydroxyalkylamino group Chemical group 0.000 claims description 6
- 238000002560 therapeutic procedure Methods 0.000 claims description 6
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical class OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 5
- 125000005110 aryl thio group Chemical group 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 4
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 4
- 125000001769 aryl amino group Chemical group 0.000 claims description 4
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 4
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
- 125000006262 isopropyl amino sulfonyl group Chemical group 0.000 claims description 4
- 125000006261 methyl amino sulfonyl group Chemical group [H]N(C([H])([H])[H])S(*)(=O)=O 0.000 claims description 4
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 2
- 125000004689 alkyl amino carbonyl alkyl group Chemical group 0.000 claims description 2
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 2
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 2
- 125000005097 aminocarbonylalkyl group Chemical group 0.000 claims description 2
- 125000001691 aryl alkyl amino group Chemical group 0.000 claims description 2
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 2
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 2
- 125000005141 aryl amino sulfonyl group Chemical group 0.000 claims description 2
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
- 125000005164 aryl thioalkyl group Chemical group 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000002837 carbocyclic group Chemical group 0.000 claims description 2
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 2
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical group C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 claims description 2
- 125000005241 heteroarylamino group Chemical group 0.000 claims description 2
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 2
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 2
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
- 125000004999 nitroaryl group Chemical group 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 2
- 125000003107 substituted aryl group Chemical group 0.000 claims description 2
- 102000010907 Cyclooxygenase 2 Human genes 0.000 claims 75
- 150000002431 hydrogen Chemical group 0.000 claims 62
- 125000001309 chloro group Chemical group Cl* 0.000 claims 10
- 125000001145 hydrido group Chemical group *[H] 0.000 claims 6
- 239000003757 phosphotransferase inhibitor Substances 0.000 claims 5
- ZFKBWSREWJOSSJ-VIFPVBQESA-N (2s)-6,8-dichloro-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound ClC1=CC(Cl)=C2O[C@H](C(F)(F)F)C(C(=O)O)=CC2=C1 ZFKBWSREWJOSSJ-VIFPVBQESA-N 0.000 claims 4
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims 4
- LPEFUBDIAFWXAA-UHFFFAOYSA-N 4-[2-(3-methylcyclohexyl)-1,3-oxazol-5-yl]benzenesulfonamide Chemical group C1C(C)CCCC1C1=NC=C(C=2C=CC(=CC=2)S(N)(=O)=O)O1 LPEFUBDIAFWXAA-UHFFFAOYSA-N 0.000 claims 3
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 3
- MNJVRJDLRVPLFE-UHFFFAOYSA-N etoricoxib Chemical group C1=NC(C)=CC=C1C1=NC=C(Cl)C=C1C1=CC=C(S(C)(=O)=O)C=C1 MNJVRJDLRVPLFE-UHFFFAOYSA-N 0.000 claims 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 3
- DEBZQUFVQZPPLC-UHFFFAOYSA-N 2h-chromene-3-carboxylic acid Chemical compound C1=CC=C2OCC(C(=O)O)=CC2=C1 DEBZQUFVQZPPLC-UHFFFAOYSA-N 0.000 claims 2
- NONBXOPYDWLZGR-UHFFFAOYSA-N 6-chloro-8-methyl-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound C1=C(C(O)=O)C(C(F)(F)F)OC2=C1C=C(Cl)C=C2C NONBXOPYDWLZGR-UHFFFAOYSA-N 0.000 claims 2
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 2
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims 2
- AVCMFIJXDZYZOT-VIFPVBQESA-N (2s)-6-chloro-2-(trifluoromethyl)-1,2-dihydroquinoline-3-carboxylic acid Chemical compound ClC1=CC=C2N[C@H](C(F)(F)F)C(C(=O)O)=CC2=C1 AVCMFIJXDZYZOT-VIFPVBQESA-N 0.000 claims 1
- 125000004869 2,2-dimethylpropylcarbonyl group Chemical group CC(CC(=O)*)(C)C 0.000 claims 1
- IWTSTYWGRNOWJQ-UHFFFAOYSA-N 2-(trifluoromethyl)-3h-benzo[f]chromene-3-carboxylic acid Chemical compound C1=CC=CC2=C(C=C(C(C(=O)O)O3)C(F)(F)F)C3=CC=C21 IWTSTYWGRNOWJQ-UHFFFAOYSA-N 0.000 claims 1
- RKHGFJBYFUHPRH-UHFFFAOYSA-N 2-(trifluoromethyl)-6-(trifluoromethylsulfanyl)-2h-thiochromene-3-carboxylic acid Chemical compound FC(F)(F)SC1=CC=C2SC(C(F)(F)F)C(C(=O)O)=CC2=C1 RKHGFJBYFUHPRH-UHFFFAOYSA-N 0.000 claims 1
- LZNNMMKMGKFYLL-UHFFFAOYSA-N 2h-pyran-3-carboxylic acid Chemical compound OC(=O)C1=CC=COC1 LZNNMMKMGKFYLL-UHFFFAOYSA-N 0.000 claims 1
- BOQXSZBPNKEVNE-UHFFFAOYSA-N 2h-thiochromene-3-carboxylic acid Chemical compound C1=CC=C2SCC(C(=O)O)=CC2=C1 BOQXSZBPNKEVNE-UHFFFAOYSA-N 0.000 claims 1
- HMBUMPBGRPVQME-UHFFFAOYSA-N 6,7-dichloro-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound ClC1=C(Cl)C=C2OC(C(F)(F)F)C(C(=O)O)=CC2=C1 HMBUMPBGRPVQME-UHFFFAOYSA-N 0.000 claims 1
- QOQKUIZOHDRLNJ-UHFFFAOYSA-N 6,8-dibromo-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound BrC1=CC(Br)=C2OC(C(F)(F)F)C(C(=O)O)=CC2=C1 QOQKUIZOHDRLNJ-UHFFFAOYSA-N 0.000 claims 1
- ZFKBWSREWJOSSJ-UHFFFAOYSA-N 6,8-dichloro-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound ClC1=CC(Cl)=C2OC(C(F)(F)F)C(C(=O)O)=CC2=C1 ZFKBWSREWJOSSJ-UHFFFAOYSA-N 0.000 claims 1
- UYZVEGRAOSUKSM-UHFFFAOYSA-N 6,8-ditert-butyl-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound C1=C(C(O)=O)C(C(F)(F)F)OC2=C1C=C(C(C)(C)C)C=C2C(C)(C)C UYZVEGRAOSUKSM-UHFFFAOYSA-N 0.000 claims 1
- QWKOPKMMJYYQRU-UHFFFAOYSA-N 6-(2-methylpropylsulfamoyl)-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound O1C(C(F)(F)F)C(C(O)=O)=CC2=CC(S(=O)(=O)NCC(C)C)=CC=C21 QWKOPKMMJYYQRU-UHFFFAOYSA-N 0.000 claims 1
- YKOKTKZEGDVFHJ-UHFFFAOYSA-N 6-(2-phenylacetyl)-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound C=1C=C2OC(C(F)(F)F)C(C(=O)O)=CC2=CC=1C(=O)CC1=CC=CC=C1 YKOKTKZEGDVFHJ-UHFFFAOYSA-N 0.000 claims 1
- HFVAUKNBDGHSCR-UHFFFAOYSA-N 6-(2-phenylethylsulfamoyl)-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound C=1C=C2OC(C(F)(F)F)C(C(=O)O)=CC2=CC=1S(=O)(=O)NCCC1=CC=CC=C1 HFVAUKNBDGHSCR-UHFFFAOYSA-N 0.000 claims 1
- XRCIFEVLZNDSDG-UHFFFAOYSA-N 6-(4-hydroxybenzoyl)-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound C=1C=C2OC(C(F)(F)F)C(C(=O)O)=CC2=CC=1C(=O)C1=CC=C(O)C=C1 XRCIFEVLZNDSDG-UHFFFAOYSA-N 0.000 claims 1
- YHQKTWYBVAMUJX-UHFFFAOYSA-N 6-(benzylsulfamoyl)-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound C=1C=C2OC(C(F)(F)F)C(C(=O)O)=CC2=CC=1S(=O)(=O)NCC1=CC=CC=C1 YHQKTWYBVAMUJX-UHFFFAOYSA-N 0.000 claims 1
- LJAIXLITIWWLMU-UHFFFAOYSA-N 6-(benzylsulfamoyl)-8-chloro-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound C=1C(Cl)=C2OC(C(F)(F)F)C(C(=O)O)=CC2=CC=1S(=O)(=O)NCC1=CC=CC=C1 LJAIXLITIWWLMU-UHFFFAOYSA-N 0.000 claims 1
- DBRFBZFRUCUHKM-UHFFFAOYSA-N 6-(furan-2-ylmethylsulfamoyl)-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound C=1C=C2OC(C(F)(F)F)C(C(=O)O)=CC2=CC=1S(=O)(=O)NCC1=CC=CO1 DBRFBZFRUCUHKM-UHFFFAOYSA-N 0.000 claims 1
- MQSZXCIMIPOLLQ-UHFFFAOYSA-N 6-(tert-butylsulfamoyl)-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound O1C(C(F)(F)F)C(C(O)=O)=CC2=CC(S(=O)(=O)NC(C)(C)C)=CC=C21 MQSZXCIMIPOLLQ-UHFFFAOYSA-N 0.000 claims 1
- CSOISVJKLBMNCK-UHFFFAOYSA-N 6-(trifluoromethoxy)-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound FC(F)(F)OC1=CC=C2OC(C(F)(F)F)C(C(=O)O)=CC2=C1 CSOISVJKLBMNCK-UHFFFAOYSA-N 0.000 claims 1
- MOYKDFAFGUWTQO-UHFFFAOYSA-N 6-benzylsulfonyl-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound C=1C=C2OC(C(F)(F)F)C(C(=O)O)=CC2=CC=1S(=O)(=O)CC1=CC=CC=C1 MOYKDFAFGUWTQO-UHFFFAOYSA-N 0.000 claims 1
- OODLETPYKNYFPC-UHFFFAOYSA-N 6-bromo-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound BrC1=CC=C2OC(C(F)(F)F)C(C(=O)O)=CC2=C1 OODLETPYKNYFPC-UHFFFAOYSA-N 0.000 claims 1
- BSCFTYXHRKRJKJ-UHFFFAOYSA-N 6-bromo-8-chloro-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound BrC1=CC(Cl)=C2OC(C(F)(F)F)C(C(=O)O)=CC2=C1 BSCFTYXHRKRJKJ-UHFFFAOYSA-N 0.000 claims 1
- WTTFVQCIUHZESW-UHFFFAOYSA-N 6-bromo-8-methoxy-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound C1=C(C(O)=O)C(C(F)(F)F)OC2=C1C=C(Br)C=C2OC WTTFVQCIUHZESW-UHFFFAOYSA-N 0.000 claims 1
- VEENGDJNDWZTOU-UHFFFAOYSA-N 6-chloro-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound ClC1=CC=C2OC(C(F)(F)F)C(C(=O)O)=CC2=C1 VEENGDJNDWZTOU-UHFFFAOYSA-N 0.000 claims 1
- XCTHXVRBSIHBAC-UHFFFAOYSA-N 6-chloro-2-(trifluoromethyl)-2h-thiochromene-3-carboxylic acid Chemical compound ClC1=CC=C2SC(C(F)(F)F)C(C(=O)O)=CC2=C1 XCTHXVRBSIHBAC-UHFFFAOYSA-N 0.000 claims 1
- OQLFETWYMAJDSQ-UHFFFAOYSA-N 6-chloro-4-phenyl-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound C12=CC(Cl)=CC=C2OC(C(F)(F)F)C(C(=O)O)=C1C1=CC=CC=C1 OQLFETWYMAJDSQ-UHFFFAOYSA-N 0.000 claims 1
- FIGFIPYZSNLSOF-UHFFFAOYSA-N 6-chloro-7-ethyl-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound O1C(C(F)(F)F)C(C(O)=O)=CC2=C1C=C(CC)C(Cl)=C2 FIGFIPYZSNLSOF-UHFFFAOYSA-N 0.000 claims 1
- ZQRBVSGXWNRTHN-UHFFFAOYSA-N 6-chloro-7-methyl-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound O1C(C(F)(F)F)C(C(O)=O)=CC2=C1C=C(C)C(Cl)=C2 ZQRBVSGXWNRTHN-UHFFFAOYSA-N 0.000 claims 1
- ARTWTAYIQKFKNP-UHFFFAOYSA-N 6-chloro-7-phenyl-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound C1=C2OC(C(F)(F)F)C(C(=O)O)=CC2=CC(Cl)=C1C1=CC=CC=C1 ARTWTAYIQKFKNP-UHFFFAOYSA-N 0.000 claims 1
- QBEGCKDFGWDVKY-UHFFFAOYSA-N 6-chloro-8-ethyl-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound C1=C(C(O)=O)C(C(F)(F)F)OC2=C1C=C(Cl)C=C2CC QBEGCKDFGWDVKY-UHFFFAOYSA-N 0.000 claims 1
- CUHYRNMEWAAFPL-UHFFFAOYSA-N 6-chloro-8-fluoro-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound ClC1=CC(F)=C2OC(C(F)(F)F)C(C(=O)O)=CC2=C1 CUHYRNMEWAAFPL-UHFFFAOYSA-N 0.000 claims 1
- CBMIVBLNFVXYHN-UHFFFAOYSA-N 6-chloro-8-propan-2-yl-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound C1=C(C(O)=O)C(C(F)(F)F)OC2=C1C=C(Cl)C=C2C(C)C CBMIVBLNFVXYHN-UHFFFAOYSA-N 0.000 claims 1
- YKJCXFQLAGEPJU-UHFFFAOYSA-N 6-iodo-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound IC1=CC=C2OC(C(F)(F)F)C(C(=O)O)=CC2=C1 YKJCXFQLAGEPJU-UHFFFAOYSA-N 0.000 claims 1
- WRXXEGPVSCGBRF-UHFFFAOYSA-N 6-methylsulfonyl-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound O1C(C(F)(F)F)C(C(O)=O)=CC2=CC(S(=O)(=O)C)=CC=C21 WRXXEGPVSCGBRF-UHFFFAOYSA-N 0.000 claims 1
- GZVGBJIOQBOCCF-UHFFFAOYSA-N 6-nitro-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound [O-][N+](=O)C1=CC=C2OC(C(F)(F)F)C(C(=O)O)=CC2=C1 GZVGBJIOQBOCCF-UHFFFAOYSA-N 0.000 claims 1
- TUUVNDRPGFNCAA-UHFFFAOYSA-N 6-tert-butyl-2-(trifluoromethyl)-2h-thiochromene-3-carboxylic acid Chemical compound S1C(C(F)(F)F)C(C(O)=O)=CC2=CC(C(C)(C)C)=CC=C21 TUUVNDRPGFNCAA-UHFFFAOYSA-N 0.000 claims 1
- ZVWOGLMGGCMZOF-UHFFFAOYSA-N 7,8-dimethyl-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound C1=C(C(O)=O)C(C(F)(F)F)OC2=C(C)C(C)=CC=C21 ZVWOGLMGGCMZOF-UHFFFAOYSA-N 0.000 claims 1
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- 230000010076 replication Effects 0.000 description 1
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- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
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- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000009291 secondary effect Effects 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
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- 150000003384 small molecules Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
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- 150000003512 tertiary amines Chemical class 0.000 description 1
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- 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
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic 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
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Plant Substances (AREA)
- Plural Heterocyclic Compounds (AREA)
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JP (1) | JP2005501843A (sk) |
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AP (1) | AP2004002995A0 (sk) |
AR (1) | AR038957A1 (sk) |
AT (1) | ATE414512T1 (sk) |
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CO (1) | CO5560544A2 (sk) |
CZ (1) | CZ2004356A3 (sk) |
DE (1) | DE60229959D1 (sk) |
EA (1) | EA008137B1 (sk) |
EC (1) | ECSP045021A (sk) |
GE (1) | GEP20063868B (sk) |
HR (1) | HRP20040170A2 (sk) |
HU (1) | HUP0500424A3 (sk) |
IL (1) | IL159887A0 (sk) |
IS (1) | IS7137A (sk) |
MA (1) | MA27060A1 (sk) |
MX (1) | MXPA04001464A (sk) |
NO (1) | NO20040516L (sk) |
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OA (1) | OA12651A (sk) |
PE (1) | PE20030332A1 (sk) |
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RS (1) | RS13204A (sk) |
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UA (1) | UA77002C2 (sk) |
WO (1) | WO2003015608A2 (sk) |
ZA (1) | ZA200400849B (sk) |
Families Citing this family (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2002346457A1 (en) * | 2001-11-21 | 2003-06-10 | Pharmacia And Upjohn Company | Pharmaceutical formulations comprising indolinone derivatives |
US6747025B1 (en) | 2002-11-27 | 2004-06-08 | Allergan, Inc. | Kinase inhibitors for the treatment of disease |
AU2003295658A1 (en) * | 2002-11-27 | 2004-06-23 | Allergan, Inc. | Indol derivatives and their use as kinase inhibitors |
JP3814285B2 (ja) | 2002-12-19 | 2006-08-23 | ファイザー・インク | 眼疾患の治療に有用なプロテインキナーゼ阻害剤としての2−(1h−インダゾール−6−イルアミノ)−ベンズアミド化合物 |
US7157577B2 (en) * | 2003-03-07 | 2007-01-02 | Sugen Inc. | 5-sulfonamido-substituted indolinone compounds as protein kinase inhibitors |
US20070123593A1 (en) * | 2003-10-08 | 2007-05-31 | Rose-Marie Dannenfelser | Pharmaceutical composition comprising 5-methyl-2(2'-chloro-6'-fluoroanilino)phenylacetic acid |
WO2005118543A1 (ja) * | 2004-06-03 | 2005-12-15 | Ono Pharmaceutical Co., Ltd. | キナーゼ阻害薬およびその用途 |
US20060009510A1 (en) * | 2004-07-09 | 2006-01-12 | Pharmacia & Upjohn Company Llc | Method of synthesizing indolinone compounds |
AU2006245421A1 (en) * | 2005-05-12 | 2006-11-16 | Pfizer Inc. | Anticancer combination therapy using sunitinib malate |
US20070015728A1 (en) * | 2005-07-08 | 2007-01-18 | Ford John P | Metered-dose and safety and compliance packaging for systemic anticancer therapy |
CA2663147A1 (en) * | 2006-09-11 | 2008-03-20 | Curis, Inc. | Substituted 2-indolinone as ptk inhibitors containing a zinc binding moiety |
US20090004213A1 (en) * | 2007-03-26 | 2009-01-01 | Immatics Biotechnologies Gmbh | Combination therapy using active immunotherapy |
WO2009030270A1 (en) * | 2007-09-03 | 2009-03-12 | Novartis Ag | Dihydroindole derivatives useful in parkinson's disease |
GB0813873D0 (en) * | 2008-07-30 | 2008-09-03 | Univ Dundee | Compounds |
EP2181991A1 (en) * | 2008-10-28 | 2010-05-05 | LEK Pharmaceuticals D.D. | Novel salts of sunitinib |
EP2186809A1 (en) * | 2008-11-13 | 2010-05-19 | LEK Pharmaceuticals D.D. | New crystal form of sunitinib malate |
WO2012042421A1 (en) | 2010-09-29 | 2012-04-05 | Pfizer Inc. | Method of treating abnormal cell growth |
RU2495628C1 (ru) * | 2012-04-18 | 2013-10-20 | Государственное бюджетное учреждение здравоохранения Московской области "Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского" (ГБУЗ МО МОНИКИ им. М.Ф. Владимирского) | Способ выбора тактики лечения актинического кератоза |
TWI646091B (zh) * | 2012-12-28 | 2019-01-01 | 日商衛斯克慧特股份有限公司 | 鹽類及晶形 |
RU2015143526A (ru) * | 2013-03-13 | 2017-04-19 | Бостон Байомедикал, Инк. | Производные 3-(арил или гетероарил)метилениндолин-2-она в качестве ингибиторов киназного пути раковых стволовых клеток для лечения рака |
CN103923014A (zh) * | 2014-05-05 | 2014-07-16 | 宁夏宝马药业有限公司 | 环肌酸制备方法 |
CA3010848A1 (en) | 2016-01-08 | 2017-07-13 | Euclises Pharmaceuticals, Inc. | Combination of a chromene compound and a second active agent |
CN111759883B (zh) * | 2020-07-23 | 2021-09-17 | 浙江农林大学 | 山核桃内果皮提取物在制备抗卵巢癌产品中的应用 |
CN114853736B (zh) * | 2022-07-06 | 2022-10-21 | 北京鑫开元医药科技有限公司 | 具有trk抑制活性的化合物、制备方法、组合物及其用途 |
Family Cites Families (114)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BE553661A (sk) * | 1955-12-23 | |||
US3840597A (en) | 1971-02-24 | 1974-10-08 | Riker Laboratories Inc | Substituted 2-phenoxy alkane-sulfonanilides |
US4002749A (en) * | 1975-08-12 | 1977-01-11 | E. R. Squibb & Sons, Inc. | Substituted indolinones |
US4053613A (en) * | 1975-09-17 | 1977-10-11 | E. R. Squibb & Sons, Inc. | 1,3,thiazolinyl and 1,3 thiazinyl substituted indolinones |
DE2756113A1 (de) | 1977-12-16 | 1979-06-21 | Thomae Gmbh Dr K | Neue 4-hydroxy-2h-1,2-benzothiazin- 3-carboxamid-1,1-dioxide, verfahren zu ihrer herstellung und diese enthaltende arzneimittel |
DE3310891A1 (de) * | 1983-03-25 | 1984-09-27 | Boehringer Mannheim Gmbh, 6800 Mannheim | Neue indolinon-(2)-derivate, verfahren zu ihrer herstellung, diese verbindungen enthaltende arzneimittel und zwischenprodukte |
DE3426419A1 (de) * | 1984-07-18 | 1986-01-23 | Boehringer Mannheim Gmbh, 6800 Mannheim | Neue oxindol-derivate, verfahren zu ihrer herstellung, diese verbindungen enthaltende arzneimittel und zwischenprodukte |
DD290192A5 (de) | 1986-11-13 | 1991-05-23 | Eisai Co. Ltd,Jp | Pyridinderivat mit antiulzeroeser wirkung |
JPH0753725B2 (ja) | 1987-10-08 | 1995-06-07 | 富山化学工業株式会社 | 4h―1―ベンゾピラン―4―オン誘導体およびその塩、それらの製造法並びにそれらを含有する抗炎症剤 |
GB8816944D0 (en) * | 1988-07-15 | 1988-08-17 | Sobio Lab | Compounds |
RU2034842C1 (ru) | 1989-07-25 | 1995-05-10 | Алкалоида Ведьесети Дьяр | Производные хинолина и способ их получения |
GB9004483D0 (en) * | 1990-02-28 | 1990-04-25 | Erba Carlo Spa | New aryl-and heteroarylethenylene derivatives and process for their preparation |
US5302606A (en) * | 1990-04-16 | 1994-04-12 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Styryl-substituted pyridyl compounds which inhibit EGF receptor tyrosine kinase |
US5196446A (en) * | 1990-04-16 | 1993-03-23 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Certain indole compounds which inhibit EGF receptor tyrosine kinase |
FR2672596B1 (fr) | 1991-02-07 | 1995-07-13 | Roussel Uclaf | Nouveaux derives bicycliques azotes, leur procede de preparation, les nouveaux intermediaires obtenus, leur application a titre de medicaments et les compositions pharmaceutiques les renfermant. |
FR2676444B1 (fr) | 1991-05-16 | 1995-03-10 | Sanofi Elf | Nouveaux derives d'amino-3 pyridazines actifs sur le systeme nerveux central, procede de preparation et compositions pharmaceutiques en contenant. |
GB9115160D0 (en) * | 1991-07-12 | 1991-08-28 | Erba Carlo Spa | Methylen-oxindole derivatives and process for their preparation |
US5124347A (en) * | 1991-07-31 | 1992-06-23 | Warner-Lambert Co. | 3-5-ditertiarybutylphenyl-4-hydroxymethylidene derivatives of 1,3-dihydro-2H-indole-2-ones as antiinflammatory agents |
US5322950A (en) * | 1991-12-05 | 1994-06-21 | Warner-Lambert Company | Imidazole with angiotensin II antagonist properties |
US5389661A (en) * | 1991-12-05 | 1995-02-14 | Warner-Lambert Company | Imidazole and 1,2,4-triazole derivatives with angiotensin II antagonist properties |
FR2694004B1 (fr) * | 1992-07-21 | 1994-08-26 | Adir | Nouvelles 3-(Hydroxybenzylidényl)-indoline-2-ones et 3-(hydroxybenzylidényl)-indoline-2-thiones, leurs procédés de préparation, et les compositions pharmaceutiques qui les contiennent. |
DE69301894T2 (de) | 1992-10-28 | 1996-11-07 | Shionogi & Co | Benzylidenderivate |
US5604260A (en) | 1992-12-11 | 1997-02-18 | Merck Frosst Canada Inc. | 5-methanesulfonamido-1-indanones as an inhibitor of cyclooxygenase-2 |
GB9226855D0 (en) * | 1992-12-23 | 1993-02-17 | Erba Carlo Spa | Vinylene-azaindole derivatives and process for their preparation |
EP0759432A1 (en) | 1993-01-15 | 1997-02-26 | G.D. Searle & Co. | Use of medicaments containing 3,4-diaryl furans and analogs thereof for treating a skin-related condition |
FR2701260B1 (fr) | 1993-02-05 | 1995-05-05 | Esteve Labor Dr | Dérivés de 2-[4-(4-azolylbutyl)-1-pipérazinyl]-5-hydroxypyrimidine, leur préparation et leur application en tant que médicaments. |
US5409944A (en) | 1993-03-12 | 1995-04-25 | Merck Frosst Canada, Inc. | Alkanesulfonamido-1-indanone derivatives as inhibitors of cyclooxygenase |
TW269679B (sk) | 1993-04-27 | 1996-02-01 | Wellcome Found | |
WO1994026731A1 (en) | 1993-05-13 | 1994-11-24 | Merck Frosst Canada Inc. | 2-substituted-3,4-diarylthiophene derivatives as inhibitors of cyclooxygenase |
US5380738A (en) | 1993-05-21 | 1995-01-10 | Monsanto Company | 2-substituted oxazoles further substituted by 4-fluorophenyl and 4-methylsulfonylphenyl as antiinflammatory agents |
US5474995A (en) | 1993-06-24 | 1995-12-12 | Merck Frosst Canada, Inc. | Phenyl heterocycles as cox-2 inhibitors |
US5436265A (en) | 1993-11-12 | 1995-07-25 | Merck Frosst Canada, Inc. | 1-aroyl-3-indolyl alkanoic acids and derivatives thereof useful as anti-inflammatory agents |
US5344991A (en) | 1993-10-29 | 1994-09-06 | G.D. Searle & Co. | 1,2 diarylcyclopentenyl compounds for the treatment of inflammation |
US5475018A (en) | 1993-11-30 | 1995-12-12 | G. D. Searle & Co. | 1,5-diphenyl pyrazole compounds for treatment of inflammation |
DK0924201T3 (da) | 1993-11-30 | 2002-05-21 | Searle & Co | Tricyclisk substitueret pyrazolylbenzensulfonamider og deres anvendelse som cyclooxygenase II-inhibitorer |
US5466823A (en) | 1993-11-30 | 1995-11-14 | G.D. Searle & Co. | Substituted pyrazolyl benzenesulfonamides |
ES2133740T3 (es) | 1994-02-10 | 1999-09-16 | Searle & Co | Espiro-compuestos sustituidos para el tratamiento de la inflamacion. |
AU2424895A (en) | 1994-05-04 | 1995-11-29 | G.D. Searle & Co. | Substituted spirodienes for the treatment of inflammation |
US5418254A (en) | 1994-05-04 | 1995-05-23 | G. D. Searle & Co. | Substituted cyclopentadienyl compounds for the treatment of inflammation |
US5486534A (en) | 1994-07-21 | 1996-01-23 | G. D. Searle & Co. | 3,4-substituted pyrazoles for the treatment of inflammation |
CA2195847A1 (en) | 1994-07-27 | 1996-02-08 | John J. Talley | Substituted thiazoles for the treatment of inflammation |
US5620999A (en) | 1994-07-28 | 1997-04-15 | Weier; Richard M. | Benzenesulfonamide subtituted imidazolyl compounds for the treatment of inflammation |
US5616601A (en) | 1994-07-28 | 1997-04-01 | Gd Searle & Co | 1,2-aryl and heteroaryl substituted imidazolyl compounds for the treatment of inflammation |
RU2128175C1 (ru) | 1994-08-09 | 1999-03-27 | Эйсай Ко., Лтд. | Конденсированный пиридазин или его фармакологически приемлемая соль, средство, проявляющее ингибирующую активность в отношении циклической гмф- фосфодиэстеразы |
US5521213A (en) | 1994-08-29 | 1996-05-28 | Merck Frosst Canada, Inc. | Diaryl bicyclic heterocycles as inhibitors of cyclooxygenase-2 |
US5547975A (en) | 1994-09-20 | 1996-08-20 | Talley; John J. | Benzopyranopyrazolyl derivatives for the treatment of inflammation |
GB2294879A (en) | 1994-10-19 | 1996-05-15 | Merck & Co Inc | Cylcooxygenase-2 Inhibitors |
CA2200462A1 (en) | 1994-10-27 | 1996-05-09 | Merck Frosst Canada Inc. | Stilbene derivatives useful as cyclooxygenase-2 inhibitors |
US5739166A (en) | 1994-11-29 | 1998-04-14 | G.D. Searle & Co. | Substituted terphenyl compounds for the treatment of inflammation |
JP3181190B2 (ja) | 1994-12-20 | 2001-07-03 | 日本たばこ産業株式会社 | オキサゾール誘導体 |
JP2636819B2 (ja) | 1994-12-20 | 1997-07-30 | 日本たばこ産業株式会社 | オキサゾール系複素環式芳香族化合物 |
AU702591B2 (en) | 1994-12-21 | 1999-02-25 | Merck Frosst Canada Ltd. | Diaryl-2-(5H)-furanones as cox-2 inhibitors |
US5552422A (en) | 1995-01-11 | 1996-09-03 | Merck Frosst Canada, Inc. | Aryl substituted 5,5 fused aromatic nitrogen compounds as anti-inflammatory agents |
WO1996023786A1 (en) | 1995-01-31 | 1996-08-08 | Merck Frosst Canada Inc. | 5-methanesulfonamido-3h-isobenzofuran-1-ones as inhibitors of cyclooxygenase-2 |
US5596008A (en) | 1995-02-10 | 1997-01-21 | G. D. Searle & Co. | 3,4-Diaryl substituted pyridines for the treatment of inflammation |
US5686470A (en) | 1995-02-10 | 1997-11-11 | Weier; Richard M. | 2, 3-substituted pyridines for the treatment of inflammation |
US5633272A (en) | 1995-02-13 | 1997-05-27 | Talley; John J. | Substituted isoxazoles for the treatment of inflammation |
CN1107058C (zh) | 1995-02-13 | 2003-04-30 | G·D·瑟尔公司 | 用于治疗类症的取代的异噁唑 |
CA2212829A1 (en) | 1995-02-21 | 1996-08-29 | Jiro Takeo | Glutamic acid receptor agonist |
HUP9801602A3 (en) | 1995-04-04 | 1999-01-28 | Glaxo Group Ltd | Imidazo[1,2-a]pyridine derivatives, process for their production, pharmaceutical compositions and use thereof |
GB9507298D0 (en) * | 1995-04-07 | 1995-05-31 | Pharmacia Spa | Substituted indolylmethylene-oxindale analogues as tyrosine kinase inhibitors |
US5691374A (en) | 1995-05-18 | 1997-11-25 | Merck Frosst Canada Inc. | Diaryl-5-oxygenated-2-(5H) -furanones as COX-2 inhibitors |
CA2221692A1 (en) | 1995-05-19 | 1996-11-21 | G.D. Searle & Co. | Substituted oxazoles for the treatment of inflammation |
US5510368A (en) | 1995-05-22 | 1996-04-23 | Merck Frosst Canada, Inc. | N-benzyl-3-indoleacetic acids as antiinflammatory drugs |
US5639780A (en) | 1995-05-22 | 1997-06-17 | Merck Frosst Canada, Inc. | N-benzyl indol-3-yl butanoic acid derivatives as cyclooxygenase inhibitors |
US5643933A (en) | 1995-06-02 | 1997-07-01 | G. D. Searle & Co. | Substituted sulfonylphenylheterocycles as cyclooxygenase-2 and 5-lipoxygenase inhibitors |
CA2223154A1 (en) | 1995-06-02 | 1996-12-05 | G.D. Searle & Co. | Heterocyclo substituted hydroxamic acid derivatives as cyclooxygenase-2 and 5-lipoxygenase inhibitors |
US5880141A (en) * | 1995-06-07 | 1999-03-09 | Sugen, Inc. | Benzylidene-Z-indoline compounds for the treatment of disease |
EP0833622B8 (en) | 1995-06-12 | 2005-10-12 | G.D. Searle & Co. | Compositions comprising a cyclooxygenase-2 inhibitor and a 5-lipoxygenase inhibitor |
US6342510B1 (en) | 1995-06-12 | 2002-01-29 | G. D. Searle & Co. | Treatment of inflammation and inflammation-related disorders with a combination of a cyclooxygenase-2 inhibitors and a leukotriene B4 receptor antagonist |
US5700816A (en) | 1995-06-12 | 1997-12-23 | Isakson; Peter C. | Treatment of inflammation and inflammation-related disorders with a combination of a cyclooxygenase-2 inhibitor and a leukotriene A4 hydrolase inhibitor |
CA2180624C (en) | 1995-07-12 | 2006-12-12 | Cheuk Kun Lau | Diphenyl-1,2,3-thiadiazoles as anti-inflammatory agents |
GB9514518D0 (en) | 1995-07-15 | 1995-09-13 | Sod Conseils Rech Applic | Guanidine salt inhibitors of NO synthase and cyclooxygenase |
US5968974A (en) | 1995-07-19 | 1999-10-19 | Merck & Co., Inc. | Method of treating colonic adenomas |
ES2220983T3 (es) | 1995-07-19 | 2004-12-16 | MERCK & CO., INC. | Procedimiento de tratamiento de adenomas de colon. |
AU6981996A (en) | 1995-09-27 | 1997-04-17 | Merck Frosst Canada Inc. | Compositions for treating inflammation containing certain prostaglandins and a selective cyclooxygenase-2 inhibitor |
GB9520584D0 (en) | 1995-10-09 | 1995-12-13 | Fujisawa Pharmaceutical Co | Pyrazole derivatives,processes for preparation thereof and pharmaceutical composition comprising the same |
UA57002C2 (uk) | 1995-10-13 | 2003-06-16 | Мерк Фросст Кенада Енд Ко./Мерк Фросст Кенада Енд Сі. | Похідне (метилсульфоніл)феніл-2-(5н)-фуранону, фармацевтична композиція та спосіб лікування |
US6376733B1 (en) | 1996-01-25 | 2002-04-23 | Exxonmobil Chemical Patents Inc. | Process for production of paraxylene |
US5733909A (en) | 1996-02-01 | 1998-03-31 | Merck Frosst Canada, Inc. | Diphenyl stilbenes as prodrugs to COX-2 inhibitors |
EA199800675A1 (ru) | 1996-02-01 | 1999-02-25 | Мерк Фросст Кэнада Инк. | Дифенилстильбены как пролекарства к ингибиторам циклооксигеназы(сох-2) |
AU710675B2 (en) | 1996-02-01 | 1999-09-30 | Merck Frosst Canada Ltd. | Alkylated styrenes as prodrugs to COX-2 inhibitors |
CA2246356A1 (en) | 1996-02-13 | 1997-08-21 | G.D. Searle & Co. | Compositions comprising a cyclooxygenase-2 inhibitor and a leukotriene b4 receptor antagonist |
EP0880363B1 (en) | 1996-02-13 | 2002-09-11 | G.D. SEARLE & CO. | Combinations, having immunosuppressive effects, containing a cyclooxygenase-2 inhibitor and a leukotriene a 4 hydrolase inhibitor |
CA2246265A1 (en) | 1996-02-13 | 1997-08-21 | G.D. Searle & Co. | Combinations having immunosuppressive effects, containing cyclooxygenase-2-inhibitors and 5-lipoxygenase inhibitors |
US6180651B1 (en) | 1996-04-04 | 2001-01-30 | Bristol-Myers Squibb | Diarylmethylidenefuran derivatives, processes for their preparation and their uses in therapeutics |
US5908858A (en) | 1996-04-05 | 1999-06-01 | Sankyo Company, Limited | 1,2-diphenylpyrrole derivatives, their preparation and their therapeutic uses |
PL195955B1 (pl) | 1996-04-12 | 2007-11-30 | Searle & Co | Związek, pochodna benzenosulfonamidu, sposób jegowytwarzania, kompozycja farmaceutyczna zawierająca go oraz jego zastosowanie |
DE69733756T2 (de) * | 1996-05-03 | 2006-06-01 | Abbott Laboratories, Abbott Park | Antiangiogenische peptiden, dafür kodierende polynukleotide und verfahren zur hemmung der angiogenesis |
US5677318A (en) | 1996-07-11 | 1997-10-14 | Merck Frosst Canada, Inc. | Diphenyl-1,2-3-thiadiazoles as anti-inflammatory agents |
US5776967A (en) | 1996-07-26 | 1998-07-07 | American Home Products Corporation | Pyranoindole inhibitors of COX--2 |
FR2751966B1 (fr) | 1996-08-01 | 1998-10-30 | Union Pharma Scient Appl | Nouveaux derives 1,2-diarylindoles, leurs procedes de preparation, et leurs utilisations en therapeutique |
FR2751964B1 (fr) | 1996-08-01 | 1998-10-30 | Union Pharma Scient Appl | Nouveaux derives diarylmethylene carbocycliques, leurs procedes de preparation, et leurs utilisations en therapeutique |
US5830911A (en) | 1996-08-14 | 1998-11-03 | American Home Products Corporation | Pyranoindole and tetrahydrocarbazole inhibitors of COX-2 |
US5681842A (en) | 1996-11-08 | 1997-10-28 | Abbott Laboratories | Prostaglandin synthase-2 inhibitors |
US5869524A (en) | 1996-11-12 | 1999-02-09 | American Home Products Corporation | Indene inhibitors of COX-2 |
JPH10158234A (ja) | 1996-12-02 | 1998-06-16 | Kotobuki Seiyaku Kk | 2−フェニルアズレン誘導体及びその製造方法 |
EP0846689B1 (en) | 1996-12-09 | 2004-01-14 | Pfizer Inc. | Benzimidazole compounds |
JP4167733B2 (ja) | 1996-12-16 | 2008-10-22 | 花王株式会社 | NF−κB活性化抑制剤 |
EP0863134A1 (en) | 1997-03-07 | 1998-09-09 | Merck Frosst Canada Inc. | 2-(3,5-difluorophenyl)-3-(4-(methyl-sulfonyl)phenyl)-2-cyclopenten-1-one useful as an inhibitor of cyclooxygenase-2 |
US6077850A (en) * | 1997-04-21 | 2000-06-20 | G.D. Searle & Co. | Substituted benzopyran analogs for the treatment of inflammation |
US6133305A (en) * | 1997-09-26 | 2000-10-17 | Sugen, Inc. | 3-(substituted)-2-indolinones compounds and use thereof as inhibitors of protein kinase activity |
FR2769311B1 (fr) | 1997-10-07 | 1999-12-24 | Union Pharma Scient Appl | Nouveaux derives 3,4-diarylthiazolin-2-one ou -2-thione, leurs procedes de preparation et leurs utilisations en therapeutique |
US5972986A (en) * | 1997-10-14 | 1999-10-26 | G.D. Searle & Co. | Method of using cyclooxygenase-2 inhibitors in the treatment and prevention of neoplasia |
FR2770131A1 (fr) | 1997-10-27 | 1999-04-30 | Union Pharma Scient Appl | Nouvelle association pharmaceutique a activite analgesique |
GB2330833A (en) | 1997-10-29 | 1999-05-05 | Merck & Co Inc | PREPARATION OF 4-(4-Methylsulfonylphenyl)-2-furanones USEFUL AS COX-2 INHIBITORS |
FR2771005B1 (fr) | 1997-11-18 | 2002-06-07 | Union Pharma Scient Appl | Nouvelle association pharmaceutique a activite analgesique |
FR2771412B1 (fr) | 1997-11-26 | 2000-04-28 | Adir | Nouveaux derives de pyrrole, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
CO5031249A1 (es) | 1998-05-29 | 2001-04-27 | Sugen Inc | Pirrol substituido-2-indolinonas inhibidoras de proteinci-nasas |
MXPA01006742A (es) * | 1998-12-31 | 2004-04-21 | Sugen Inc | Compuestos 3-heteroarilidenil-2-indolinona para modular la actividad de la quinasa de proteina y para utilizarse en la quimioterapia de cancer. |
PT1255536E (pt) * | 1999-12-22 | 2006-09-29 | Sugen Inc | Derivados de indolinona para a modulacao da tirosina proteina cinase de tipo c-kit |
JP2003535038A (ja) * | 1999-12-30 | 2003-11-25 | スージェン・インコーポレーテッド | 蛋白質キナーゼ活性の調節および癌化学療法において用いるための3−ヘテロアリーリデニル−2−インドリノン化合物 |
SK287142B6 (sk) * | 2000-02-15 | 2010-01-07 | Sugen, Inc. | Inhibítory proteínkináz na báze pyrolom substituovaného 2-indolinónu, farmaceutický prípravok s ich obsahom a ich použitie |
ES2290120T3 (es) * | 2000-03-17 | 2008-02-16 | Avocet Polymer Technologies, Inc. | Procedimientos para mejorar la dimension y el aspecto de una herida. |
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