N-(heteroaryl)-1H-indole-2-carboxamide derivatives and their use as vanilloid TRPV1 receptor ligands

A compound of the formula (I)

• wherein
• n is equal to 0, 1, 2 or 3;
• X1, X2, X3, X4, Z1, Z2, Z3, Z4 and Z5 represent, independently of each other, a hydrogen or halogen atom or a C1-C6-alkyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C3-alkylene, C1-C6-fluoroalkyl, C1-C6-alkoxy, C1-C6-fluoroalkoxy, cyano, C(O)NR1R2, nitro, NR1R2, C1-C6-thioalkyl, —S(O)—C1-C6-alkyl, —S(O)2—C1-C6-alkyl, SO2NR1R2, NR3COR4, NR3SO2R5 or aryl group, the aryl being optionally substituted with one or more substituents chosen from a halogen and a C1-C6-alkyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C3-alkylene, C1-C6-fluoroalkyl, C1-C6-alkoxy, C1-C6-fluoroalkoxy, nitro or cyano group;
• R1 and R2 represent, independently of each other, a hydrogen atom or a C1-C6-alkyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C3-alkylene or aryl group;
• or R1 and R2 form, together with the nitrogen atom that bears them, an azetidine, pyrrolidine, piperidine, azepine, morpholine, thiomorpholine, piperazine or homopiperazine group, said group being optionally substituted with a C1-C6-alkyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C3-alkylene or aryl group;
• R3 and R4 represent, independently of each other, a hydrogen atom or a C1-C6-alkyl or aryl group;
• R5 represents a C1-C6-alkyl or aryl group;
• W represents a fused bicyclic group of formula:
• linked to the nitrogen atom via positions 1, 2, 3 or 4;
• A represents a 5- to 7-membered heterocycle comprising from one to three heteroatoms chosen from O, S and N, wherein if one or more sulfur and/or nitrogen atoms are present, they are optionally in the oxidized form;
• the carbon atom(s) of A being optionally substituted with one or more groups chosen from a hydrogen atom and a C1-C6-alkyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C3-alkylene, C1-C6-fluoroalkyl, aryl, aryl-C1-C6-alkylene, oxo or thio group;
• the nitrogen atom(s) of A being optionally substituted with R6 when the nitrogen is adjacent to a carbon atom substituted with an oxo group, or with R7 in the other cases;
• R6 represents a hydrogen atom or a C1-C6-alkyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C3-alkylene, C1-C6-fluoroalkyl, aryl-C1-C6-alkylene or aryl group;
• R7 represents a hydrogen atom or a C1-C6-alkyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C3-alkylene, C1-C6-fluoroalkyl, aryl-C1-C6-alkylene, C1-C6-alkyl-C(O)—, C3-C7-cycloalkyl-C1-C3-alkylene-(CO)—, C1-C6-fluoroalkyl-C(O)—, C3-C7-cycloalkyl-C(O)—, aryl-C(O)—, aryl-C1-C6-alkylene-C(O)—, C1-C6-alkyl-S(O)2—, C1-C6-fluoroalkyl-S(O)2—, C3-C7-cycloalkyl-S(O)2—, C3-C7-cycloalkyl-C1-C3-alkylene-S(O)2—, aryl-S(O)2- or aryl-C1-C6-alkylene-S(O)2— or aryl group;
• and
• W is other than indolyl;
• or an addition salt thereof;
• and
• with the proviso that when W represents a quinolyl, X2 and X3 cannot be halogen;
• and
• with the proviso the following compounds are excluded:
• N-(quinol-7-yl)-1-benzyl-6-bromo-1H-indole-2-carboxamide;
• N-(quinol-7-yl)-1-benzyl-5-bromo-1H-indole-2-carboxamide;
• and
• N-(quinol-7-yl)-6-bromo-1-(4-(trifluoromethyl)benzyl)-1H-indole-2-carboxamide.