Bicyclic derivatives of azabicyclic carboxamides, preparation thereof and therapeutic use thereof

A compound corresponding to formula (I):

• wherein:
• X1, X2, X3 and X4 represent, independently of each other, a group C—R1;
• W represents an oxygen or sulfur atom;
• n is equal to 0, 1, 2 or 3;
• Y represents an aryl or a heteroaryl optionally substituted with one or more groups chosen from a halogen atom, a group C1-C6-alkyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C3-alkylene, C1-C6-fluoroalkyl, hydroxyl, C1-C6-alkoxy, C3-C7-cycloalkyloxy, C3-C7-cycloalkyl-C1-C6-alkylene-O—, C1-C6-fluoroalkoxy, cyano, C(O)NR4R5, nitro, NR4R5, C1-C6-thioalkyl, thiol, —S(O)—C1-C6-alkyl, —S(O)2—C1-C6-alkyl, SO2NR4R5, NR6C(O)R7, NR6SO2R8, C(O)NR4R5, OC(O)NR4R5, —Si—(C1-C6-alkyl)3, —SF5, aryl-C1-C5-alkylene or aryl, heteroaryl-C1-C5-alkylene or heteroaryl;
• the groups C1-C6-alkyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C3-alkylene, C1-C6-fluoroalkyl, C1-C6-alkoxy, C3-C7-cycloalkyloxy, C3-C7-cycloalkyl-C1-C6-alkylene-O— being optionally substituted with a hydroxyl group, C1-C6-alkoxy or NR4R5, the aryl and heteroaryl groups being optionally substituted with one or more substituents R9, which may be identical to or different from each other;
• A represents the group of formula:
• Z1, Z2, Z3 and Z4 represent, independently of each other, a nitrogen atom, a carbon atom or a group C—R2,
• at least one from among Z1, Z2, Z3 and Z4 corresponding to a nitrogen atom and
• one from among Z1, Z2, Z3 and Z4, corresponding to a carbon atom, being bonded to the nitrogen atom of the amide or of the thioamide of formula (I);
• Ra and Rb form, together with the carbon atoms that bear them,
• either a partially unsaturated cycloalkyl, or an aryl;
• or a heterocycle, or a heteroaryl, which is 5- to 7-membered, comprising from 1 to 3 heteroatoms chosen from O, S and N;
• wherein when Ra and Rb together form, with the carbon atoms that bear them, a 5-membered ring, this ring comprising a nitrogen atom and carbon atoms, this ring being partially saturated or unsaturated, is excluded;
• the partially unsaturated cycloalkyl, the aryl, the heterocycle or the heteroaryl are optionally substituted with one or more substituents R3;
• R1 is chosen from a hydrogen atom, a halogen atom, C1-C6-alkyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C3-alkylene, C1-C6-fluoroalkyl, aryloxy-C1-C6-alkyl, heteroaryloxy-C1-C6-alkyl, aryl-C1-C3-alkylenoxy-C1-C6-alkyl, heteroaryl-C1-C3-alkylenoxy-C1-C6-alkyl, arylthio-C1-C6-alkyl, heteroarylthio-C1-C6-alkyl, aryl-C1-C3-alkylene-thio-C1-C6-alkyl, heteroaryl-C1-C3-alkylene-thio-C1-C6-alkyl, C1-C6-alkoxy, C3-C7-cycloalkyloxy, C3-C7-cycloalkyl-C1-C3-alkylenoxy, C1-C6-fluoroalkoxy, cyano, C(O)NR4R5, nitro, NR4R5, C1-C6-thioalkyl, C3-C7-cycloalkylthio, C3-C7-cycloalkyl-C1-C3-alkylene-thio, —S(O)—C1-C6-alkyl, —S(O)—C3-C7-cycloalkyl, —S(O)—C1-C3-alkylene-C3-C7-cycloalkyl, 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—, SO2NR4R5, —Si—(C1-C6-alkyl)3, —SF5, NR6C(O)R7, NR6SO2R8, C(O)NR4R5, OC(O)NR4R5, aryl, heteroaryl, aryl-C1-C5-alkylene, heteroaryl-C1-C5-alkylene, aryloxy, arylthio, heteroaryloxy or heteroarylthio;
• the heteroaryl or aryl groups being optionally substituted with one or more substituents R9, which may be identical to or different from each other;
• R2 represents a hydrogen atom, a halogen atom or a group C1-C6-alkyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C3-alkylene, C1-C6-fluoroalkyl, C1-C6-alkoxy, C3-C7-cycloalkyloxy, C3-C7-cycloalkyl-C1-C3-alkylene-O—, hydroxyl, thiol or C1-C6-fluoroalkoxy;
• R3 represents, when it is borne by a carbon atom, a hydrogen atom or a hydroxyl, thiol, C1-C6-alkyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C3-alkylene, C1-C6-fluoroalkyl, C1-C6-alkoxy, C3-C7-cycloalkyloxy, C3-C7-cycloalkyl-C1-C3-alkylenoxy, C1-C6-alkoxy-C1-C3-alkylene, C3-C7-cycloalkyloxy-C1-C3-alkylene, C3-C7-cycloalkyl-C1-C3-alkylenoxy-C1-C3-alkylene, C(O)NR4R5, C(O)O—C1-C6-alkyl, CO2H, oxo or thio group;
• the groups C1-C6-alkyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C3-alkylene, C1-C6-fluoroalkyl, C1-C6-alkoxy, C3-C7-cycloalkyloxy, C3-C7-cycloalkyl-C1-C3-alkylenoxy, C1-C6-alkoxy-C1-C3-alkylene, C3-C7-cycloalkyloxy-C1-C3-alkylene, C3-C7-cycloalkyl-C1-C3-alkylenoxy-C1-C3-alkylene are optionally substituted with a hydroxyl group, C1-C6-alkoxy, —OC(O)—C1-C6-alkyl or NR4R5;
• or
• R3 represents, when it is borne by a nitrogen atom, a hydrogen atom or a group C1-C6-alkyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C3-alkylene, C1-C6-fluoroalkyl, aryl-C(O)—, C1-C6-alkyl-C(O)—, C3-C7-cycloalkyl-C(O)—, C3-C7-cycloalkyl-C1-C3-alkylene-C(O)—, C1-C6-fluoroalkyl-C(O)—, aryl-S(O), C1-C6-alkyl-S(O)—, C1-C6-fluoroalkyl-S(O)—, aryl-S(O)2—, 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—, C1-C6-alkyl-O—C(O)—, aryl-C1-C3-alkyl-O—C(O)—, C3-C7-cycloalkyl-O—C(O)—, C3-C7-cycloalkyl-C1-C3-alkylene-O—C(O)—, C1-C6-fluoroalkyl-O—C(O), aryl-O—C(O)—, heteroaryl-O—C(O)—, heteroaryl or aryl;
• the heteroaryl and aryl groups being optionally substituted with one or more substituents R9, which may be identical to or different from each other;
• the groups C1-C6-alkyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C3-alkylene and C1-C6-fluoroalkyl are optionally substituted with a hydroxyl group, C1-C6-alkoxy or NR4R5;
• R4 and R5, represent, independently of each other, a hydrogen atom or a group C1-C6-alkyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C3-alkylene, aryl-C1-C5-alkylene or aryl, or R4 and R5 together form, with the nitrogen atom that bears them, an azetidine, pyrrolidine, piperidine, azepine, morpholine, thiomorpholine, piperazine or homopiperazine group;
• the group NR4R5 being optionally substituted with a group C1-C6-alkyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C3-alkylene, aryl-C1-C6-alkylene, aryl, heteroaryl, aryl-S(O)2—, 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-C(O)—, C1-C6-alkyl-C(O)—, C3-C7-cycloalkyl-C(O)—, C3-C7-cycloalkyl-C1-C3-alkylene-C(O)—, C1-C6-fluoroalkyl-C(O)—, hydroxyl, C1-C6-alkyloxy, C3-C7-cycloalkyloxy, C3-C7-cycloalkyl-C1-C3-alkylenoxy, C1-C6-fluoroalkyl, aryloxy-C1-C6-alkylene, aryloxy, heteroaryloxy-C1-C6-alkylene or heteroaryloxy;
• R6 and R7 represent, independently of each other, a hydrogen atom or a group C1-C6-alkyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C3-alkylene, aryl-C1-C6-alkylene or aryl;
• the aryl group being optionally substituted with one or more substituents chosen from a halogen atom and a group C1-C6-alkyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C3-alkylene, C1-C6-fluoroalkyl, C1-C6-alkoxy, C3-C7-cycloalkyloxy, C3-C7-cycloalkyl-C1-C3-alkylenoxy, C1-C6-fluoroalkoxy, nitro or cyano;
• or R6 and R7 together form a 4- to 7-membered lactam comprising the nitrogen atom and the C(O) group that bear them;
• R8 represents a group C1-C6-alkyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C3-alkylene, aryl-C1-C6-alkylene or aryl;
• the aryl group being optionally substituted with one or more substituents chosen from a halogen atom, a group C1-C6-alkyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C3-alkylene, C1-C6-fluoroalkyl, C1-C6-alkoxy, C3-C7-cycloalkyloxy, C3-C7-cycloalkyl-C1-C3-alkylenoxy, C1-C6-fluoroalkoxy, nitro or cyano;
• or R6 and R8 together form a 4- to 7-membered sultam comprising the nitrogen atom and the S(O)2 group that bear them;
• R9 represents a halogen atom, a group C1-C6-alkyl, C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C3-alkylene, C1-C6-fluoroalkyl, C1-C6-alkoxy, C3-C7-cycloalkyloxy, C3-C7-cycloalkyl-C1-C3-alkylenoxy, or C1-C6-fluoroalkoxy;
• these groups being optionally substituted with a group OH, C1-C6-alkoxy or NR4R5;
• or alternatively R9 represents a nitro group, cyano or NR4R5;
• the sulfur atom(s) of the compound of general formula (I) optionally being in oxidized form;
• the nitrogen atom(s) of the compound of general formula (I) optionally being in oxidized form;
• or an acid-addition salt thereof.