Bicyclic heterocyclic compounds as protein tyrosine kinase inhibitors

摘要

The invention relates to new bicyclic heterocyclic derivative compounds of formula (I): wherein R1, q, A, B, X1, X2, X3, X4, X5 and R2 are as defined herein, to pharmaceutical compositions comprising said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.;

主权项

1. A method for the treatment of a disease state or condition selected from multiple myeloma, bladder carcinoma, hepatocellular carcinoma, oral squamous cell carcinoma, cervical carcinoma, and urothelial carcinoma, which method comprises administering to a subject in need thereof a compound of the formula (I):wherein
represents a single or double bond, such that at least one bond within the 5 membered ring system is a double bond; Ring A may be optionally substituted by 1, 2 or 3 Ra groups; B represents a —V-carbocyclic group or a —W-heterocyclyl group wherein said carbocyclic and heterocyclyl groups may be optionally substituted by 1, 2 or 3 Ra groups; Re, Rf and Rw independently represent hydrogen or C1-6 alkyl; Ra represents halogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C3-8 cycloalkenyl, —ORx, —O—(CH2)n—ORx, haloC1-6 alkyl, haloC1-6 alkoxy, C1-6 alkanol, ═O, ═S, nitro, Si(Rx)4, —(CH2)s—CN, —S—Rx, —SO—Rx, —SO2—Rx, —CORx, —(CRxRy)s—COORz, —(CH2)s—CONRxRy, —(CH2)s—NRxRy, —(CH2)s—NRxCORy, —(CH2)s—NRxSO2—Ry, —(CH2)s—NH—SO2—NRxRy, —OCONRxRy, —(CH2)s—NRxCO2Ry, —O—(CH2)s—CRxRy—(CH2)t—ORz or —(CH2)s—SO2NRxRy groups; Rx, Ry and Rz independently represent hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkanol, hydroxy, C1-6 alkoxy, haloC1-6 alkyl, —CO—(CH2)n—C1-6 alkoxy, C3-8 cycloalkyl or C3-8 cycloalkenyl; R7 and R8 independently represent hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C3-8 cycloalkenyl, aryl, heterocyclyl or R7 and R8 together with the nitrogen atom to which they are attached may form a nitrogen containing heterocyclyl ring, wherein said C1-6 alkyl, aryl and heterocyclyl may be optionally substituted by 1, 2 or 3 Rb groups; R1 and Rb independently represent an Ra group or a —Y-carbocyclic or —Z-heterocyclyl group wherein said carbocyclic and heterocyclyl groups may be optionally substituted by 1, 2 or 3 Ra groups; V and W independently represent a bond or a —(CReRf)n— group; Y and Z independently represent a bond, —CO—(CH2)s—, —COO—, —(CH2)n—, —NRx—(CH2)s—, —(CH2)s—NRx—, —CONRx—, —NRxCO—, —SO2NRx—, —NRxSO2, —NRxCONRy—, —NRxCSNRy—, —O—(CH2)s—, —(CH2)s—O—, S—, —SO— or —(CH2)s—SO2—; n represents an integer from 1-4; s and t independently represent an integer from 0-4; q represents an integer from 0-2; or a pharmaceutically acceptable salt or solvate thereof.