THIENO[3,2-C]PYRIDIN-4(5H)-ONES AS BET INHIBITORS

摘要

Thienopyridone compounds of formula (I):;;or a salt thereof, pharmaceutical compositions containing such compounds and their use in therapy, in particular in the treatment of diseases or conditions for which a bromodomain inhibitor is indicated.

主权项

1. A compound of formula (I):wherein:
W is N or C—R8; X is N, CH or C(CH3); Z is N or C—R14; Y is N or C—R5 (subject to proviso that no more than 2 of W, X, Y and Z are N); R1 is C1-4alkyl; R2 is H, OH, C1-4alkyl, —N(CH3)2, —NH(CH3), halo, —CF3, —NH2, —OC1-4alkyl, —NHC(O)H, —NHC(O)C1-4alkyl, —N(CH3)C(O)C1-4alkyl, —NHCH(CH3)CH2OCH3, —N(CH3)CH2CH2OCH3, —OCH2CH2OCH3, —OCH2CH2CH2OH, —OCH(CH3)CH2OCH3, or R2 is a group selected from -G-CH2CH(R3)(R4), -G-CH(R3)(R4) and -G-R3 in which
G is NH, N(CH3), O, C(O)NH or NHC(O);R3 is phenyl, pyridinyl, C3-7cycloalkyl or a heterocycle optionally substituted by ═O; andR4 is H or C1-4 alkyl; R5 is H, C1-4alkyl, halo, —CF3, CN, OH, —OC1-4 alkyl, —CH2NH2, —OCF3 or —SO2CH3; R6 is —NR11R12 or a group R7; D is CH or N; E is N, O, CH or SO2; R7, when present, is H, OH, C1-4alkyl, —NH2, —SO2C1-4alkyl, —SO2phenyl, —SO2benzyl, —SO2N(CH3)2, —NHSO2CH3, —C(O)C1-4alkyl or —C(O)phenyl; R6 is H, C1-4alkyl, halo, —CF3, CN, OH, —OC1-4 alkyl, —OCF3, —OCH2phenyl or —OCH2C3-7cycloalkyl; R8 is H, C1-4alkyl, —C(O)NH2, —CO2CH3, —CF3, halo, OH, —OC1-4alkyl, —CH2OH, —C(O)NHCH3, —C(O)N(CH3)2, —CH2OC1-4alkyl, —CH2OCH2C3-7cycloalkyl or oxo; R10 is H, C1-4alkyl, —C(O)NH2, —CO2CH3, —CF3, halo, OH or —OC1, alkyl; R11 is H, C1-4alkyl or SO2CH3; R12 is H, C1-4alkyl, C1-4alkyleneNHR13, C1-4alkyleneOH, SO2CH3, a heterocycle or a heterocycle comprising SO2; R13 is H or SO2CH3; R14 is H, C1-4alkyl or NHC(O)C1-4alkyl; and n and m are each an integer independently selected from 0, 1 and 2; or a salt thereof.