HRP20040170A2 - Combination therapy for the treatment of cancer - Google Patents
Combination therapy for the treatment of cancer Download PDFInfo
- Publication number
- HRP20040170A2 HRP20040170A2 HR20040170A HRP20040170A HRP20040170A2 HR P20040170 A2 HRP20040170 A2 HR P20040170A2 HR 20040170 A HR20040170 A HR 20040170A HR P20040170 A HRP20040170 A HR P20040170A HR P20040170 A2 HRP20040170 A2 HR P20040170A2
- Authority
- HR
- Croatia
- Prior art keywords
- group
- hydrogen
- carboxylic acid
- alkyl
- trifluoromethyl
- Prior art date
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- 206010028980 Neoplasm Diseases 0.000 title claims description 83
- 201000011510 cancer Diseases 0.000 title claims description 46
- 238000011282 treatment Methods 0.000 title claims description 46
- 238000002648 combination therapy Methods 0.000 title description 8
- 150000001875 compounds Chemical class 0.000 claims description 268
- -1 piperazin-1-yl-methyl Chemical group 0.000 claims description 267
- 229910052739 hydrogen Inorganic materials 0.000 claims description 214
- 239000001257 hydrogen Substances 0.000 claims description 213
- 125000000217 alkyl group Chemical group 0.000 claims description 210
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 205
- 238000000034 method Methods 0.000 claims description 154
- 150000002431 hydrogen Chemical group 0.000 claims description 121
- 125000003118 aryl group Chemical group 0.000 claims description 117
- 125000003545 alkoxy group Chemical group 0.000 claims description 85
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 75
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 68
- 125000005843 halogen group Chemical group 0.000 claims description 65
- 125000001072 heteroaryl group Chemical group 0.000 claims description 63
- 150000003839 salts Chemical class 0.000 claims description 51
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 40
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 35
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 32
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 claims description 31
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 29
- 239000003909 protein kinase inhibitor Substances 0.000 claims description 29
- 108010037462 Cyclooxygenase 2 Proteins 0.000 claims description 27
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 27
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 21
- 125000000623 heterocyclic group Chemical group 0.000 claims description 21
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 20
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 19
- 229940043355 kinase inhibitor Drugs 0.000 claims description 19
- 125000001188 haloalkyl group Chemical group 0.000 claims description 18
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 17
- PIGFYZPCRLYGLF-UHFFFAOYSA-N Aluminum nitride Chemical compound [Al]#N PIGFYZPCRLYGLF-UHFFFAOYSA-N 0.000 claims description 16
- 125000004104 aryloxy group Chemical group 0.000 claims description 15
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 150000003254 radicals Chemical class 0.000 claims description 14
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 14
- 229940124639 Selective inhibitor Drugs 0.000 claims description 13
- 229940093444 Cyclooxygenase 2 inhibitor Drugs 0.000 claims description 12
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 claims description 12
- 125000004953 trihalomethyl group Chemical group 0.000 claims description 12
- 125000004429 atom Chemical group 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical group 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 125000002252 acyl group Chemical group 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 9
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 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
- 125000006260 ethylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 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 description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
- 239000001301 oxygen Substances 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
- 125000002947 alkylene 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
- 125000001153 fluoro group Chemical group F* 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
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 7
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 6
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound 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 6
- 125000005191 hydroxyalkylamino group Chemical group 0.000 claims description 6
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 125000005110 aryl thio group Chemical group 0.000 claims description 5
- 125000001246 bromo group Chemical group Br* 0.000 claims description 5
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 5
- 239000011593 sulfur Substances 0.000 claims description 5
- 229940122204 Cyclooxygenase inhibitor Drugs 0.000 claims description 4
- 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
- 125000000304 alkynyl 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
- 125000000392 cycloalkenyl 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
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 3
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical class OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 2
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 2
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 2
- 125000000278 alkyl amino alkyl 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
- 125000004103 aminoalkyl 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
- 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
- 125000001624 naphthyl group Chemical group 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 12
- 125000001145 hydrido group Chemical group *[H] 0.000 claims 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims 4
- 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 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 3
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims 3
- 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 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
- 239000003757 phosphotransferase inhibitor Substances 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
- MQHRBURXMDMQCY-UHFFFAOYSA-N 2-(trifluoromethyl)-2h-benzo[g]chromene-3-carboxylic acid Chemical compound C1=CC=C2C=C(OC(C(C(=O)O)=C3)C(F)(F)F)C3=CC2=C1 MQHRBURXMDMQCY-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
- LPEFUBDIAFWXAA-UHFFFAOYSA-N 4-[2-(3-methylcyclohexyl)-1,3-oxazol-5-yl]benzenesulfonamide Chemical compound C1C(C)CCCC1C1=NC=C(C=2C=CC(=CC=2)S(N)(=O)=O)O1 LPEFUBDIAFWXAA-UHFFFAOYSA-N 0.000 claims 1
- KJOSDRUNXOPTEP-UHFFFAOYSA-N 5,7-dichloro-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound C1=C(Cl)C=C2OC(C(F)(F)F)C(C(=O)O)=CC2=C1Cl KJOSDRUNXOPTEP-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
- XSYDNZXQHVDCQR-UHFFFAOYSA-N 6,7-difluoro-2-(trifluoromethyl)-1,2-dihydroquinoline-3-carboxylic acid Chemical compound FC1=C(F)C=C2NC(C(F)(F)F)C(C(=O)O)=CC2=C1 XSYDNZXQHVDCQR-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
- YCPMOEZRKIIFKJ-UHFFFAOYSA-N 6,8-dichloro-2-(trifluoromethyl)-2h-thiochromene-3-carboxylic acid Chemical compound ClC1=CC(Cl)=C2SC(C(F)(F)F)C(C(=O)O)=CC2=C1 YCPMOEZRKIIFKJ-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
- WRWBASOXAVOXNF-UHFFFAOYSA-N 6-(dimethylsulfamoyl)-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound O1C(C(F)(F)F)C(C(O)=O)=CC2=CC(S(=O)(=O)N(C)C)=CC=C21 WRWBASOXAVOXNF-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
- ZACVSMBOYXVARY-UHFFFAOYSA-N 6-(methylsulfamoyl)-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound O1C(C(F)(F)F)C(C(O)=O)=CC2=CC(S(=O)(=O)NC)=CC=C21 ZACVSMBOYXVARY-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
- KZZNJUPPFLIVKP-UHFFFAOYSA-N 6-chloro-1-methyl-2-(trifluoromethyl)-2h-quinoline-3-carboxylic acid Chemical compound ClC1=CC=C2N(C)C(C(F)(F)F)C(C(O)=O)=CC2=C1 KZZNJUPPFLIVKP-UHFFFAOYSA-N 0.000 claims 1
- GAQLCAMYZGDGAI-UHFFFAOYSA-N 6-chloro-2-(trifluoromethyl)-1,2-dihydro-1,8-naphthyridine-3-carboxylic acid Chemical compound ClC1=CN=C2NC(C(F)(F)F)C(C(=O)O)=CC2=C1 GAQLCAMYZGDGAI-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
- SNCBDVLECJZNBB-UHFFFAOYSA-N 6-chloro-7-(4-nitrophenoxy)-2-(trifluoromethyl)-2h-chromene-3-carboxylic acid Chemical compound C1=C2OC(C(F)(F)F)C(C(=O)O)=CC2=CC(Cl)=C1OC1=CC=C([N+]([O-])=O)C=C1 SNCBDVLECJZNBB-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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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PCT/US2002/025797 WO2003015608A2 (en) | 2001-08-15 | 2002-08-15 | Combination therapy for the treatment of cancer |
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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 |
CN1250526C (zh) | 1998-05-29 | 2006-04-12 | 苏根公司 | 吡咯取代的2-吲哚满酮蛋白激酶抑制剂 |
BR9916735A (pt) * | 1998-12-31 | 2001-09-25 | Sugen Inc | Compostos de 3-heteroarilidenil-2-indolinona para a modulação da atividade das cinases protéicas e para uso na quimioterapia do cancêr |
DE60029138T2 (de) * | 1999-12-22 | 2007-06-06 | Sugen, Inc., San Francisco | Verwendung von Indolinonverbindungen zur Herstellung von Pharmazeutika für die Modulation der Funktion c-kit Proteintyrosinkinase |
WO2001049287A1 (en) * | 1999-12-30 | 2001-07-12 | Sugen, Inc. | 3-heteroarylidenyl-2-indolinone compounds for modulating protein kinase activity and for use in cancer chemotherapy |
WO2001060814A2 (en) * | 2000-02-15 | 2001-08-23 | Sugen, Inc. | Pyrrole substituted 2-indolinone protein kinase inhibitors |
DE60128673D1 (de) * | 2000-03-17 | 2007-07-12 | Avocet Polymer Technologies In | Verfahren zur verbesserung der grösse und des aussehens einer wunde |
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