Quinoline and quinoxaline derivatives as inhibitors of kinase enzymatic activity

A compound of formula (IA) or (IB), or a salt, or N-oxide thereof:

• wherein
• Y1 is a bond, or —C(═O);
• L1 is a divalent radical of formula -(Alk1)m(Q1)n(Alk2)p- wherein
• m, n and p are independently 0 or 1,
• Q1 is (i) an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5-13 ring members, or (ii), in the case where p is 0, a divalent radical of formula -Q2-X2— wherein X2 is —O—, —S— or NRA— wherein RA is hydrogen or optionally substituted C1-C3 alkyl, and Q2 is an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5-13 ring members,
• Alk1 and Alk2 independently represent optionally substituted divalent C3-C7 cycloalkyl radicals, or optionally substituted straight or branched, C1-C6 alkylene, C2-C6 alkenylene, or C2-C6 alkynylene radicals which may optionally contain or terminate in an ether (—O—), thioether (—S—) or amino (—NRA—) link wherein RA is hydrogen or optionally substituted C1-C3 alkyl;
• R6 is C1-C4 alkyl;
• RB hydrogen or C1-C3 alkyl;
• each L2 independently represents a radical of formula *—Z-(AlK4)b- wherein the bond marked * is directly connected to the nitrogen atom and wherein b is 0 or 1;
• Alk4 independently represents optionally substituted divalent C3-C7 cycloalkyl radicals, or optionally substituted straight or branched, C1-C6 alkylene, C2-C6 alkenylene, or C2-C6 alkynylene radical which may optionally contain or terminate in an ether (—O—), thioether (—S—) or amino (—NRA—) link wherein RA is hydrogen or optionally substituted C1-C3 alkyl;
• Z represents a —CO—, —SO2—, *—CONRB—, or *—CSNRB— radical, wherein the bond marked * is directly connected to the nitrogen atom;
• r is 0 or 1;
• and
• ring A is an optionally substituted 1,4-phenylene ring;
• and ring B is a mono- or bi-cyclic carbocyclic or heterocyclic ring or ring system having up to 12 ring atoms;
• R is a radical of formula (X) or (Y):
• wherein
• R1 is an ester group of formula —(C═O)OR9 which is hydrolysable by one or more intracellular carboxylesterase enzymes to a carboxylic acid group wherein R9 is
• (i) R7R8CH— wherein R7 is optionally substituted (C1-C3)alkyl-(Z1)a—(C1-C3)alkyl- or C2-C3)alkenyl-(Z1)a—(C1-C3)alkyl- wherein a is 0 or 1 and Z1 is —O—, —S—, or —NH—, and R8 is hydrogen or (C1-C3)alkyl- or R7 and R8 taken together with the carbon to which they are attached form an optionally substituted C3-C7 cycloalkyl ring or an optionally substituted heterocyclic ring of 5- or 6-ring atoms;
• or
• (ii) optionally substituted phenyl or monocyclic heterocyclic having 5 or 6 ring atoms;
• R4 is hydrogen;
• or optionally substituted C1-C6 alkyl, C3-C7 cycloalkyl, aryl, aryl(C1-C6 alkyl)-, heteroaryl, heteroaryl(C1-C6 alkyl)-, —(C═O)R3, —(C═O)OR3, or —(C═O)NR3 wherein R3 is hydrogen or optionally substituted (C1-C6)alkyl, C3-C7 cycloalkyl, aryl, aryl(C1-C6 alkyl)-, heteroaryl, or heteroaryl(C1-C6 alkyl)-;
• R41 is hydrogen or optionally substituted C1-C6 alkyl;
• and
• D is a monocyclic heterocyclic ring of 5 or 6 ring atoms wherein R1 is linked to a ring carbon adjacent the ring nitrogen shown, and ring D is optionally fused to a second carbocyclic or heterocyclic ring of 5 or 6 ring atoms in which case the bond shown intersected by a wavy line may be from a ring atom in said second ring.