Substituted Oxazole- and Thiazole-Based Carboxamide and Urea Derivatives as Vanilloid Receptor Ligands II

A substituted compound of general formula (I),

• wherein
• X represents O or S;
• Y represents O, S or N—CN;
• Z represents N(R3b) or C(R4aR4b);
• R1 represents aryl or heteroaryl,
• wherein said aryl or heteroaryl may be unsubstituted or mono- or independently polysubstituted by one or more substituents, selected from the group consisting of H, F, Cl, Br, CN, OH, C1-4-alkyl, hydroxy-C1-4-alkyl, halo-C1-4-alkyl, cyano-C1-4-alkyl, C1-4-alkoxy-C1-4-alkyl, hydroxy-C1-4-alkoxy, halo-C1-4-alkoxy, cyano-C1-4-alkoxy;
• C1-4-alkoxy-C1-4-alkoxy;
• C1-4-alkylS(═O), hydroxy-C1-4-alkylS(═O), halo-C1-4-alkylS(═O), cyano-C1-4-alkylS(═O), C1-4-alkoxy-C1-4-alkylS(═O), C1-4-alkylS(═O)2, hydroxy-C1-4-alkylS(═O)2, halo-C1-4-alkylS(═O)2, cyano-C1-4-alkylS(═O)2, C1-4-alkoxy-C1-4-alkylS(═O)2, H2N, (C1-4-alkyl)(H)N, (hydroxy-C1-4-alkyl)(H)N, (halo-C1-4-alkyl)(H)N, (cyano-C1-4-alkyl)(H)N, (C1-4-alkoxy-C1-4-alkyl)(H)N, (C3-6-cycloalkyl)(H)N, (C3-7-heterocyclo-alkyl)(H)N, (C1-4-alkyl)2N, (hydroxy-C1-4-alkyl)(C1-4-alkyl)N, (halo-C1-4-alkyl)(C1-4-alkyl)N, (cyano-C1-4-alkyl)(C1-4-alkyl)N, (C1-4-alkoxy-C1-4-alkyl)(C1-4-alkyl)N, (C3-6-cycloalkyl)(C1-4-alkyl)N, (C3-7-heterocycloalkyl)(C1-4-alkyl)N, (hydroxy-C1-4-alkyl)2N, (C3-6-cyclo-alkyl)(hydroxy-C1-4-alkyl)N, (C3-7-heterocycloalkyl)(hydroxy-C1-4-alkyl)N,
• R2 represents C1-4-alkyl, hydroxy-C1-4-alkyl, halo-C1-4-alkyl, cyano-C1-4-alkyl, C1-4-alkoxy-C1-4-alkyl, C3-6-cycloalkyl or (C3-6-cycloalkyl)-C1-4-alkyl;
• R3a and R3b each independently represent H, C1-4-alkyl, hydroxy-C1-4-alkyl, halo-C1-4-alkyl, cyano-C1-4-alkyl or C1-4-alkoxy-C1-4-alkyl;
• R4a and R4b each independently represent H, F, Cl, CN, C1-4-alkyl, hydroxy-C1-4-alkyl, halo-C1-4-alkyl, cyano-C1-4-alkyl or C1-4-alkoxy-C1-4-alkyl;
• or
• R4a and R4b together with the carbon atom connecting them form a C3-6-cycloalkyl or a C3-7-heterocycloalkyl;
• and
• Ar represents aryl or heteroaryl,
• wherein said aryl or heteroaryl may be condensed with an aromatic or aliphatic ring to form a bicycle,
• and wherein said aryl or heteroaryl and said condensed aromatic or aliphatic ring each independently may be unsubstituted or mono- or independently polysubstituted by one or more substituents, selected from the group consisting of F, Cl, Br, CN, OH, ═O, C1-4-alkyl, hydroxy-C1-4-alkyl, halo-C1-4-alkyl, cyano-C1-4-alkyl, C1-4-alkoxy-C1-4-alkyl, hydroxy-C1-4-alkoxy, halo-C1-4-alkoxy, cyano-C1-4-alkoxy, C1-4-alkoxy-C1-4-alkoxy, hydroxy-C1-4-alkoxy-C1-4-alkyl, C1-4-alkylS(═O), hydroxy-C1-4-alkylS(═O), halo-C1-4-alkylS(═O), cyano-C1-4-alkylS(═O), C1-4-alkoxy-C1-4-alkylS(═O), C1-4-alkylS(═O)2, hydroxy-C1-4-alkylS(═O)2, halo-C1-4-alkylS(═O)2, cyano-C1-4-alkylS(═O)2, C1-4-alkoxy-C1-4-alkylS(═O)2, C1-4-alkylS(═O)C1-4-alkyl, hydroxy-C1-4-alkylS(═O)C1-4-alkyl, C1-4-alkylS(═O)2C1-4-alkyl, hydroxy-C1-4-alkylS(═O)2C1-4-alkyl, H2N, (C1-4-alkyl)(H)N, (hydroxy-C1-4-alkyl)(H)N, (halo-C1-4-alkyl)(H)N, (cyano-C1-4-alkyl)(H)N, (C1-4-alkoxy-C1-4-alkyl)(H)N, (C3-6-cycloalkyl)(H)N, (C3-7-heterocycloalkyl)(H)N, (C1-4-alkyl)2N, (hydroxy-C1-4-alkyl)(C1-4-alkyl)N, (halo-C1-4-alkyl)(C1-4-alkyl)N, (cyano-C1-4-alkyl)(C1-4-alkyl)N, (C1-4-alkoxy-C1-4-alkyl)(C1-4-alkyl)N, (C3-6-cyclo-alkyl)(C1-4-alkyl)N, (C3-7-heterocycloalkyl)(C1-4-alkyl)N, (hydroxy-C1-4-alkyl)2N, (C3-6-cycloalkyl)(hydroxy-C1-4-alkyl)N, (C3-7-heterocycloalkyl)-(hydroxy-C1-4-alkyl)N, (H)2NC1-4-alkyl, [(C1-4-alkyl)(H)N](C1-4-alkyl), [(hydroxy-C1-4-alkyl)(H)N](C1-4-alkyl), [(halo-C1-4-alkyl)(H)N](C1-4-alkyl), [(cyano-C1-4-alkyl)(H)N](C1-4-alkyl), [(C1-4-alkoxy-C1-4-alkyl)(H)N](C1-4-alkyl), [(C3-6-cycloalkyl)(H)N](C1-4-alkyl), [(C3-7-heterocycloalkyl)-(H)N](C1-4-alkyl), [(C1-4-alkyl)2N](C1-4-alkyl), [(hydroxy-C1-4-alkyl)(C1-4-alkyl)N](C1-4-alkyl), [(halo-C1-4-alkyl)(C1-4-alkyl)N](C1-4-alkyl), [(cyano-C1-4-alkyl)(C1-4-alkyl)N](C1-4-alkyl), [(C1-4-alkoxy-C1-4-alkyl)(C1-4-alkyl)N](C1-4-alkyl), [(C3-6-cycloalkyl)(C1-4-alkyl)N](C1-4-alkyl), [(C3-7-heterocycloalkyl)(C1-4-alkyl)N](C1-4-alkyl), [(hydroxy-C1-4-alkyl)2N](C1-4-alkyl), [(C3-6-cycloalkyl)(hydroxy-C1-4-alkyl)N](C1-4-alkyl), [(C3-7-hetero-cycloalkyl)(hydroxy-C1-4-alkyl)N](C1-4-alkyl), H2NC(═O), (C1-4-alkyl)(H)NC(═O), (hydroxy-C1-4-alkyl)(H)NC(═O), (halo-C1-4-alkyl)(H)N—C(═O), (cyano-C1-4-alkyl)(H)NC(═O), (C1-4-alkoxy-C1-4-alkyl)(H)—NC(═O), (C3-6-cycloalkyl)(H)NC(═O), (C3-7-heterocyclo-alkyl)(H)NC(═O), (C1-4-alkyl)2NC(═O), (hydroxy-C1-4-alkyl)(C1-4-alkyl)NC(═O), (halo-C1-4-alkyl)(C1-4-alkyl)NC(═O), (cyano-C1-4-alkyl)(C1-4-alkyl)NC(═O), (C1-4-alkoxy-C1-4-alkyl)(C1-4-alkyl)NC(═O), (C3-6-cyclo-alkyl)(C1-4-alkyl)NC(═O), (C3-7-heterocycloalkyl)(C1-4-alkyl)NC(═O), (hydroxy-C1-4-alkyl)2NC(═O), (C3-6-cycloalkyl)(hydroxy-C1-4-alkyl)NC(═O), (C3-7-heterocycloalkyl)(hydroxy-C1-4-alkyl)NC(═O), H2NS(═O)2, (C1-4-alkyl)(H)NS(═O)2, (hydroxy-C1-4-alkyl)(H)NS(═O)2, (halo-C1-4-alkyl)(H)NS(═O)2, (cyano-C1-4-alkyl)(H)NS(═O)2, (C1-4-alkoxy-C1-4-alkyl)(H)NS(═O)2, (C3-6-cycloalkyl)(H)N S(═O)2, (C3-7-heterocycloalkyl)(H)NS(═O)2, (C1-4-alkyl)2NS(═O)2, (hydroxy-C1-4-alkyl)(C1-4-alkyl)NS(═O)2, (halo-C1-4-alkyl)(C1-4-alkyl)NS(═O)2, (cyano-C1-4-alkyl)(C1-4-alkyl)NS(═O)2, (C1-4-alkoxy-C1-4-alkyl)(C1-4-alkyl)NS(═O)2, (C3-6-cycloalkyl)(C1-4-alkyl)NS(═O)2, (C3-7-heterocyclo-alkyl)(C1-4-alkyl)NS(═O)2, (hydroxy-C1-4-alkyl)2NS(═O)2, (C3-6-cyclo-alkyl)(hydroxy-C1-4-alkyl)NS(═O)2, (C3-7-heterocycloalkyl)(hydroxy-C1-4-alkyl)NS(═O)2, H2NS(═O)2N(H)C1-4-alkyl, (C1-4-alkyl)(H)NS(═O)2N(H)C1-4-alkyl, (hydroxy-C1-4-alkyl)(H)NS(═O)2N(H)C1-4-alkyl, (C1-4-alkyl)2NS(═O)2N(H)C1-4-alkyl, (C1-4-alkyl)S(═O)2N(H)C1-4-alkyl, (hydroxy-C1-4-alkyl)S(═O)2N(H)C1-4-alkyl, C3-6-cycloalkyl, (C3-6-cycloalkyl)-C1-4-alkyl, (C3-6-cycloalkyl)-C1-4-alkoxy, C3-7-hetero-cycloalkyl, (C3-7-heterocycloalkyl)-C1-4-alkyl, (C3-7-heterocycloalkyl)-C1-4-alkoxy,
• wherein said C3-6-cycloalkyl or C3-7-heterocycloalkyl may be unsubstituted or mono- or independently polysubstituted by one or more substituents, selected from H, F, Cl, Br, CN, OH, ═O, C1-4-alkyl, hydroxy-C1-4-alkyl, halo-C1-4-alkyl, cyano-C1-4-alkyl, C1-4-alkoxy-C1-4-alkyl, hydroxy-C1-4-alkoxy, halo-C1-4-alkoxy, cyano-C1-4-alkoxy and C1-4-alkoxy-C1-4-alkoxy;
• aryl, heteroaryl, (aryl)C1-4-alkyl or (heteroaryl)C1-4-alkyl,
• wherein said aryl or heteroaryl may be unsubstituted or mono- or independently polysubstituted by one or more substituents, selected from the group consisting of H, F, Cl, Br, CN, OH, C1-4-alkyl, hydroxy-C1-4-alkyl, halo-C1-4-alkyl, cyano-C1-4-alkyl, C1-4-alkoxy-C1-4-alkyl, hydroxy-C1-4-alkoxy, halo-C1-4-alkoxy, cyano-C1-4-alkoxy and C1-4-alkoxy-C1-4-alkoxy;
• optionally in the form of a single stereoisomer or a mixture of stereoisomers, in the form of the free compound and/or a physiologically acceptable salt or a solvate thereof.