Patent RU-2718876-C2 (RU)
Inventor: TSYAN Syanpin
IPC: C07D471/04
Filed: 2014-08-22
Granted: 2020-04-15
Abstract: FIELD: medicine; pharmaceuticals. 
     SUBSTANCE: invention relates to a novel compound of formula Ia or a pharmaceutically acceptable salt thereof. Compounds have inhibitory activity on EGFR, EGFR L858R, EGFR T790M, EGFR L858R/T790M BTK, KDR or JAK3 and can be used in treating cancer, such as non-small-cell lung cancer, breast cancer, colon cancer, thyroid cancer or ovarian cancer. In formula Ia, 
     
       
     
     X 1  is CR 2  or N; X 2  is CR 11 ; X 3  is CR 12 ; X 4  is CR 13 ; X 5  is CR 14 ; R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 11 , R 12 , R 13  and R 14  independently represent hydrogen, cyano, halogen, unsubstituted or substituted C 1 -C 6  alkoxy, unsubstituted or substituted cycloalkyloxy, unsubstituted or substituted geterotsikloalkiloksi, unsubstituted or substituted C 1 -C 6  alkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted amino, unsubstituted or substituted alkoxycarbonyl, or unsubstituted or substituted aminocarbonyl; R 8 , R 9  and R 10  independently represent hydrogen, cyano, halogen, optionally substituted C 1 -C 6  alkoxy, optionally substituted alkoxycarbonyl or E, where at least one of R 8 , R 9  and R 10  is E; and E is selected from 
     
       
     
     where alkoxy is -O- (unsubstituted or substituted C 1 -C 6  alkyl); alkoxycarbonyl is -(C=O)-(unsubstituted or substituted C 1 -C 6  alkoxy); heterocycloalkyloxy is -O-(unsubstituted or substituted heterocycloalkyl); cycloalkyloxy represents -O-(unsubstituted or substituted C 3 -C 7  cycloalkyl); aminocarbonyl is -C(=O)-NR b R c , where R b  is H, unsubstituted or substituted C 1 -C 6  alkyl, unsubstituted or substituted C 3 -C 7  cycloalkyl or unsubstituted or substituted heterocycloalkyl; and R c  is hydrogen or unsubstituted or substituted C 1 -C 4  alkyl; or R b  and R c , taken together with the nitrogen atom to which they are bonded, form an unsubstituted or substituted 4–8-member nitrogen-containing heterocycloalkyl, optionally containing 1 or 2 additional heteroatoms selected from O, N and S, in heterocycloalkyl ring; heteroaryl is 5–6-membered aromatic ring containing 1–3 heteroatoms selected from N, O and S; heterocycloalkyl is 3–8-member non-aromatic monocyclic ring containing 1–3 heteroatoms selected from N, O and S; substituted amino is -NHR d  or -NR d R e , where R d  is independently unsubstituted or substituted C 1 -C 6  alkyl, unsubstituted or substituted C 3 -C 7  cycloalkyl or unsubstituted or substituted heterocycloalkyl; and R e  are independently selected from unsubstituted or substituted C 1 -C 6  alkyl, unsubstituted or substituted C 3 -C 7  cycloalkyl or unsubstituted or substituted heterocycloalkyl; and where substituted alkyl, substituted heterocycloalkyl, substituted heteroaryl and substituted cycloalkyl are substituted with one or more substituents independently representing C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, -OC 1 -C 4  alkyl, -C 1 -C 4  alkyl-OH, -C 1 -C 4  alkyl-OC 1 -C 4  alkyl, -OC 1 -C 4  haloalkyl, halogen, -OH, -NH 2 , -C 1 -C 4  alkyl-NH 2 , -N(C 1 -C 4  alkyl) (C 1 -C 4  alkyl), -NH(C 1 -C 4  alkyl), cyano, oxo (as a substitute for cycloalkyl and heterocycloalkyl), -CO 2 H, -C(O)OC 1 -C 4  alkyl, -CON(C 1 -C 4  alkyl)(C 1 -C 4  alkyl), -CONH-(C 1 -C 4  alkyl), -CONH 2 , -NHC(O)-(C 1 -C 4  alkyl), -N(C 1 -C 4  alkyl)C(O)-(C 1 -C 4  alkyl), -C(O)-C 1 -C 4  alkyl, -C(O)-C 1 -C 4  haloalkyl, -OC(O)-C 1 -C 4  alkyl, -SO 2 (C 1 -C 4  alkyl), -SO 2 (C 1 -C 4  haloalkyl), -SO 2 NH 2 , -SO 2 NH(C 1 -C 4  alkyl), -NHSO 2 (C 1 -C 4  alkyl) or -NHSO 2 (C 1 -C 4  haloalkyl). 
     EFFECT: disclosed are certain chemical compounds, compositions and methods. 
     67 cl, 7 tbl, 175 ex