JP2010500994A - Pi3kおよびmekモジュレーターを使用する方法 - Google Patents
Pi3kおよびmekモジュレーターを使用する方法 Download PDFInfo
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- JP2010500994A JP2010500994A JP2009524671A JP2009524671A JP2010500994A JP 2010500994 A JP2010500994 A JP 2010500994A JP 2009524671 A JP2009524671 A JP 2009524671A JP 2009524671 A JP2009524671 A JP 2009524671A JP 2010500994 A JP2010500994 A JP 2010500994A
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- Prior art keywords
- amino
- phenyl
- quinoxalin
- methyloxy
- sulfonyl
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- 238000000034 method Methods 0.000 title claims abstract description 54
- 108091007960 PI3Ks Proteins 0.000 title claims abstract description 40
- 102000010400 1-phosphatidylinositol-3-kinase activity proteins Human genes 0.000 title claims 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 359
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 40
- 201000011510 cancer Diseases 0.000 claims abstract description 27
- -1 —NHS (O) 2 R 8 Chemical group 0.000 claims description 584
- 229910052739 hydrogen Inorganic materials 0.000 claims description 331
- 239000001257 hydrogen Substances 0.000 claims description 330
- 125000000217 alkyl group Chemical group 0.000 claims description 256
- 125000003118 aryl group Chemical group 0.000 claims description 219
- 125000001072 heteroaryl group Chemical group 0.000 claims description 210
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 192
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 178
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 170
- 125000003342 alkenyl group Chemical group 0.000 claims description 149
- 150000002431 hydrogen Chemical class 0.000 claims description 146
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 116
- 125000003545 alkoxy group Chemical group 0.000 claims description 84
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 81
- 125000001188 haloalkyl group Chemical group 0.000 claims description 80
- 125000000304 alkynyl group Chemical group 0.000 claims description 73
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 72
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 71
- 125000003107 substituted aryl group Chemical group 0.000 claims description 65
- 125000000623 heterocyclic group Chemical group 0.000 claims description 64
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 63
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 60
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 58
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 57
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 54
- 150000003839 salts Chemical class 0.000 claims description 54
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 50
- 229910052799 carbon Inorganic materials 0.000 claims description 48
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 41
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 40
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 39
- 239000000203 mixture Substances 0.000 claims description 37
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 36
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 34
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 32
- 239000012453 solvate Substances 0.000 claims description 29
- 125000004043 oxo group Chemical group O=* 0.000 claims description 27
- 125000003282 alkyl amino group Chemical group 0.000 claims description 26
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 26
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 24
- 125000002252 acyl group Chemical group 0.000 claims description 22
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims description 22
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 21
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 19
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 17
- 125000004104 aryloxy group Chemical group 0.000 claims description 17
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 15
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 13
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 12
- 230000035772 mutation Effects 0.000 claims description 12
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 12
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 11
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 11
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 9
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 9
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 8
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 7
- BSMCAPRUBJMWDF-KRWDZBQOSA-N cobimetinib Chemical compound C1C(O)([C@H]2NCCCC2)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F BSMCAPRUBJMWDF-KRWDZBQOSA-N 0.000 claims description 6
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 5
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- 201000001441 melanoma Diseases 0.000 claims description 5
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 4
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 4
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 4
- 206010033128 Ovarian cancer Diseases 0.000 claims description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 claims description 4
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 claims description 4
- 108010091528 Proto-Oncogene Proteins B-raf Proteins 0.000 claims description 4
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 4
- COACPTNNJAFVAN-UHFFFAOYSA-N [3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-(3-hydroxyazetidin-1-yl)methanone Chemical compound C1C(O)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F COACPTNNJAFVAN-UHFFFAOYSA-N 0.000 claims description 4
- VALZSZJVEFACEZ-UHFFFAOYSA-N azetidine-3-carboxamide Chemical compound NC(=O)C1CNC1 VALZSZJVEFACEZ-UHFFFAOYSA-N 0.000 claims description 4
- 201000010881 cervical cancer Diseases 0.000 claims description 4
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 3
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 3
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims description 3
- 208000008383 Wilms tumor Diseases 0.000 claims description 3
- 125000000732 arylene group Chemical group 0.000 claims description 3
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 3
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000005349 heteroarylcycloalkyl group Chemical group 0.000 claims description 3
- 125000005549 heteroarylene group Chemical group 0.000 claims description 3
- 229940124530 sulfonamide Drugs 0.000 claims description 3
- DBTDBYINUJMLRZ-UHFFFAOYSA-N (3,3-difluoroazetidin-1-yl)-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]methanone Chemical compound C=1C=C(I)C=C(F)C=1NC1=C(F)C(F)=CC=C1C(=O)N1CC(F)(F)C1 DBTDBYINUJMLRZ-UHFFFAOYSA-N 0.000 claims description 2
- AMKMWZPNFOTRDH-UHFFFAOYSA-N (3-aminoazetidin-1-yl)-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]methanone Chemical compound C1C(N)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F AMKMWZPNFOTRDH-UHFFFAOYSA-N 0.000 claims description 2
- ZZJMLFCTJLGTEI-UHFFFAOYSA-N (3-aminoazetidin-1-yl)-[4-(2-fluoro-4-iodoanilino)thiophen-3-yl]methanone Chemical compound C1C(N)CN1C(=O)C1=CSC=C1NC1=CC=C(I)C=C1F ZZJMLFCTJLGTEI-UHFFFAOYSA-N 0.000 claims description 2
- OIEUKOXYYRCJOB-UHFFFAOYSA-N 1-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzoyl]-n-hydroxyazetidine-2-carboxamide Chemical compound ONC(=O)C1CCN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F OIEUKOXYYRCJOB-UHFFFAOYSA-N 0.000 claims description 2
- VGQZTOCHLVGGBK-UHFFFAOYSA-N 1-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzoyl]-n-hydroxyazetidine-3-carboxamide Chemical compound C1C(C(=O)NO)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F VGQZTOCHLVGGBK-UHFFFAOYSA-N 0.000 claims description 2
- OUZFPOWROZRFOA-UHFFFAOYSA-N 1-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzoyl]-n-methylazetidine-3-carboxamide Chemical compound C1C(C(=O)NC)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F OUZFPOWROZRFOA-UHFFFAOYSA-N 0.000 claims description 2
- JNRJARCELIUHEU-UHFFFAOYSA-N 1-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzoyl]azetidin-3-one Chemical compound C=1C=C(I)C=C(F)C=1NC1=C(F)C(F)=CC=C1C(=O)N1CC(=O)C1 JNRJARCELIUHEU-UHFFFAOYSA-N 0.000 claims description 2
- QYQLVTVZLMBZKM-UHFFFAOYSA-N 1-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzoyl]azetidine-2-carboxylic acid Chemical compound OC(=O)C1CCN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F QYQLVTVZLMBZKM-UHFFFAOYSA-N 0.000 claims description 2
- KDMCTGAOBPQHRZ-UHFFFAOYSA-N 1-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzoyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F KDMCTGAOBPQHRZ-UHFFFAOYSA-N 0.000 claims description 2
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 2
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims description 2
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 2
- 206010014733 Endometrial cancer Diseases 0.000 claims description 2
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
- 102000018471 Proto-Oncogene Proteins B-raf Human genes 0.000 claims description 2
- JLVKONGOFKFMSG-UHFFFAOYSA-N [3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-(3-ethenyl-3-hydroxyazetidin-1-yl)methanone Chemical compound C1C(O)(C=C)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F JLVKONGOFKFMSG-UHFFFAOYSA-N 0.000 claims description 2
- RWBREZLXOJSIET-UHFFFAOYSA-N [3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-(3-ethyl-3-hydroxyazetidin-1-yl)methanone Chemical compound C1C(CC)(O)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F RWBREZLXOJSIET-UHFFFAOYSA-N 0.000 claims description 2
- KDQMGKLTDPLARQ-UHFFFAOYSA-N [3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-(3-hydroxy-3-methylazetidin-1-yl)methanone Chemical compound C1C(C)(O)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F KDQMGKLTDPLARQ-UHFFFAOYSA-N 0.000 claims description 2
- DYULZSLYHAGCKA-UHFFFAOYSA-N [3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-(3-hydroxyiminoazetidin-1-yl)methanone Chemical compound C1C(=NO)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F DYULZSLYHAGCKA-UHFFFAOYSA-N 0.000 claims description 2
- VELUNLAKLQWONH-UHFFFAOYSA-N [3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-(3-methoxyazetidin-1-yl)methanone Chemical compound C1C(OC)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F VELUNLAKLQWONH-UHFFFAOYSA-N 0.000 claims description 2
- WCXUOAHSMZLHHJ-UHFFFAOYSA-N [3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-[2-(hydroxymethyl)azetidin-1-yl]methanone Chemical compound OCC1CCN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F WCXUOAHSMZLHHJ-UHFFFAOYSA-N 0.000 claims description 2
- KTWSVKCOTQHEKG-UHFFFAOYSA-N [3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-[3-(1,2-dihydroxyethyl)-3-hydroxyazetidin-1-yl]methanone Chemical compound C1C(C(O)CO)(O)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F KTWSVKCOTQHEKG-UHFFFAOYSA-N 0.000 claims description 2
- UPYUDZFHRQOICR-UHFFFAOYSA-N [3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-[3-(2,3-dihydroxypropyl)-3-hydroxyazetidin-1-yl]methanone Chemical compound C1C(CC(O)CO)(O)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F UPYUDZFHRQOICR-UHFFFAOYSA-N 0.000 claims description 2
- FHMBCSSWNHGFON-UHFFFAOYSA-N [3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-[3-(hydroxymethyl)azetidin-1-yl]methanone Chemical compound C1C(CO)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F FHMBCSSWNHGFON-UHFFFAOYSA-N 0.000 claims description 2
- HUUPFBKNECWODN-UHFFFAOYSA-N [3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-[3-[(dimethylamino)methyl]-3-hydroxyazetidin-1-yl]methanone Chemical compound C1C(CN(C)C)(O)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F HUUPFBKNECWODN-UHFFFAOYSA-N 0.000 claims description 2
- OQQZKLZIDXLDLJ-UHFFFAOYSA-N [3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-[3-hydroxy-3-(hydroxymethyl)azetidin-1-yl]methanone Chemical compound C1C(CO)(O)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F OQQZKLZIDXLDLJ-UHFFFAOYSA-N 0.000 claims description 2
- RSECRMOYVYYDGW-UHFFFAOYSA-N [3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-[3-hydroxy-3-(pyrrolidin-1-ylmethyl)azetidin-1-yl]methanone Chemical compound C1N(C(=O)C=2C(=C(F)C(F)=CC=2)NC=2C(=CC(I)=CC=2)F)CC1(O)CN1CCCC1 RSECRMOYVYYDGW-UHFFFAOYSA-N 0.000 claims description 2
- JMVZVVBBNYXKEV-UHFFFAOYSA-N [3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]methanone Chemical compound C1C(O)(C(F)(F)F)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F JMVZVVBBNYXKEV-UHFFFAOYSA-N 0.000 claims description 2
- BSMCAPRUBJMWDF-QGZVFWFLSA-N [3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-[3-hydroxy-3-[(2r)-piperidin-2-yl]azetidin-1-yl]methanone Chemical compound C1C(O)([C@@H]2NCCCC2)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F BSMCAPRUBJMWDF-QGZVFWFLSA-N 0.000 claims description 2
- ROZUZKLWYFJFQI-UHFFFAOYSA-N [3-(1-aminoethyl)-3-hydroxyazetidin-1-yl]-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]methanone Chemical compound C1C(C(N)C)(O)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F ROZUZKLWYFJFQI-UHFFFAOYSA-N 0.000 claims description 2
- GLTAPZSWBNABCW-UHFFFAOYSA-N [3-(aminomethyl)-3-hydroxyazetidin-1-yl]-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]methanone Chemical compound C1C(CN)(O)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F GLTAPZSWBNABCW-UHFFFAOYSA-N 0.000 claims description 2
- LSGPROFVHFKBPK-UHFFFAOYSA-N [3-(butylamino)azetidin-1-yl]-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]methanone Chemical compound C1C(NCCCC)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F LSGPROFVHFKBPK-UHFFFAOYSA-N 0.000 claims description 2
- ZGLBDNNACLJNLJ-UHFFFAOYSA-N [3-(diethylaminomethyl)-3-hydroxyazetidin-1-yl]-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]methanone Chemical compound C1C(CN(CC)CC)(O)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F ZGLBDNNACLJNLJ-UHFFFAOYSA-N 0.000 claims description 2
- LTRWLJURZZHUDX-UHFFFAOYSA-N [4-(2-fluoro-4-iodoanilino)thiophen-3-yl]-(3-hydroxyazetidin-1-yl)methanone Chemical compound C1C(O)CN1C(=O)C1=CSC=C1NC1=CC=C(I)C=C1F LTRWLJURZZHUDX-UHFFFAOYSA-N 0.000 claims description 2
- YVSXASJEPXDDQH-UHFFFAOYSA-N azetidin-1-yl-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]methanone Chemical compound C=1C=C(I)C=C(F)C=1NC1=C(F)C(F)=CC=C1C(=O)N1CCC1 YVSXASJEPXDDQH-UHFFFAOYSA-N 0.000 claims description 2
- KKCWBKUOPJMUQV-UHFFFAOYSA-N azetidine-2-carboxamide Chemical compound NC(=O)C1CCN1 KKCWBKUOPJMUQV-UHFFFAOYSA-N 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
- 230000001404 mediated effect Effects 0.000 claims description 2
- SBWFTBDLVKJJKG-UHFFFAOYSA-N n-[1-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzoyl]azetidin-3-yl]-2-methylpropanamide Chemical compound C1C(NC(=O)C(C)C)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F SBWFTBDLVKJJKG-UHFFFAOYSA-N 0.000 claims description 2
- FVMSYKSCRZQSRY-UHFFFAOYSA-N n-[1-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzoyl]azetidin-3-yl]-3,4-dihydroxybutanamide Chemical compound C1C(NC(=O)CC(O)CO)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F FVMSYKSCRZQSRY-UHFFFAOYSA-N 0.000 claims description 2
- VFYTWFMPMFOXFU-UHFFFAOYSA-N n-[1-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzoyl]azetidin-3-yl]acetamide Chemical compound C1C(NC(=O)C)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F VFYTWFMPMFOXFU-UHFFFAOYSA-N 0.000 claims description 2
- NMDYHLPRZQJKGH-UHFFFAOYSA-N n-[1-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzoyl]azetidin-3-yl]formamide Chemical compound C=1C=C(I)C=C(F)C=1NC1=C(F)C(F)=CC=C1C(=O)N1CC(NC=O)C1 NMDYHLPRZQJKGH-UHFFFAOYSA-N 0.000 claims description 2
- JAUYYOYZXIPIHA-UHFFFAOYSA-N n-[1-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzoyl]azetidin-3-yl]methanesulfonamide Chemical compound C1C(NS(=O)(=O)C)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F JAUYYOYZXIPIHA-UHFFFAOYSA-N 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 201000002528 pancreatic cancer Diseases 0.000 claims description 2
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- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 2
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- CYVGSEKMUPDFOK-UHFFFAOYSA-N n-[3-[[3-(3,5-dimethoxyanilino)quinoxalin-2-yl]sulfamoyl]phenyl]pyridine-4-carboxamide Chemical compound COC1=CC(OC)=CC(NC=2C(=NC3=CC=CC=C3N=2)NS(=O)(=O)C=2C=C(NC(=O)C=3C=CN=CC=3)C=CC=2)=C1 CYVGSEKMUPDFOK-UHFFFAOYSA-N 0.000 claims 1
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- A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
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- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- C—CHEMISTRY; METALLURGY
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- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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| US83830706P | 2006-08-16 | 2006-08-16 | |
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Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013151570A (ja) * | 2006-08-16 | 2013-08-08 | Exelixis Inc | Pi3kおよびmekモジュレーターを使用する方法 |
| JP2010513288A (ja) * | 2006-12-14 | 2010-04-30 | エグゼリクシス, インコーポレイテッド | Mek阻害剤の使用方法 |
| JP2013507415A (ja) * | 2009-10-12 | 2013-03-04 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | Pi3k阻害剤とmek阻害剤の併用 |
| JP2015038110A (ja) * | 2009-10-12 | 2015-02-26 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | Pi3k阻害剤とmek阻害剤の併用 |
| JP2013543008A (ja) * | 2010-11-19 | 2013-11-28 | グラクソスミスクライン、インテレクチュアル、プロパティー、ナンバー2、リミテッド | Braf阻害剤による治療方法 |
| JP2020520949A (ja) * | 2017-05-22 | 2020-07-16 | ユニバーシティ オブ ヴァージニア パテント ファウンデーションUniversity Of Verginia Patent Foundation | 組成物、並びにミトコンドリア脱共役剤を調製及び使用する方法 |
| JP2021525247A (ja) * | 2018-05-21 | 2021-09-24 | ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ | 複素縮合ピリドン化合物及びidh阻害剤としてのこれらの使用 |
| JP7304896B2 (ja) | 2018-05-21 | 2023-07-07 | ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ | 複素縮合ピリドン化合物及びidh阻害剤としてのこれらの使用 |
| JP2022511730A (ja) * | 2018-11-20 | 2022-02-01 | エヌフレクション セラピューティクス インコーポレイテッド | 皮膚障害の処置のためのシアノアリール-アニリン化合物 |
| JP7406264B2 (ja) | 2018-11-20 | 2023-12-27 | エヌフレクション セラピューティクス インコーポレイテッド | 皮膚障害の処置のためのシアノアリール-アニリン化合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| US20140100215A1 (en) | 2014-04-10 |
| AU2007284562A1 (en) | 2008-02-21 |
| EP2056829B1 (en) | 2012-01-04 |
| WO2008021389A2 (en) | 2008-02-21 |
| EP2056829A2 (en) | 2009-05-13 |
| CN104784695A (zh) | 2015-07-22 |
| WO2008021389A3 (en) | 2008-07-17 |
| JP2014122243A (ja) | 2014-07-03 |
| CA2658725A1 (en) | 2008-02-21 |
| JP2017226702A (ja) | 2017-12-28 |
| AU2007284562B2 (en) | 2013-05-02 |
| US8642584B2 (en) | 2014-02-04 |
| JP2013151570A (ja) | 2013-08-08 |
| HK1130438A1 (en) | 2009-12-31 |
| JP2016074743A (ja) | 2016-05-12 |
| ATE539752T1 (de) | 2012-01-15 |
| WO2008021389A8 (en) | 2009-03-12 |
| US20120302545A1 (en) | 2012-11-29 |
| EP2056829B9 (en) | 2012-09-26 |
| US20100075947A1 (en) | 2010-03-25 |
| CN101528231A (zh) | 2009-09-09 |
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