Novel triazole compounds as transforming growth factors (TGF) inhibitors

A compound of formula (Ia), (Ib), or (Ic):

• 41
• or a pharmaceutically acceptable salt, prodrug, tautomer, hydrate or solvate thereof, wherein:
• R1 is a saturated, unsaturated, or aromatic C3-C20 mono-, bi- or polycyclic ring optionally containing at least one heteroatom selected from the group consisting of N, O and S, wherein R1 can optionally be further independently substituted with at least one moiety independently selected from the group consisting of:
• carbonyl, halo, halo(C1-C6)alkyl, perhalo(C1-C6)alkyl, perhalo(C1-C6)alkoxy,
• (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, hydroxy, oxo, mercapto, (C1-C6)alkylthio, (C1-C6)alkoxy, (C5-C10)aryl or (C5-C10)heteroaryl, (C5-C10)aryloxy or (C5-C10)heteroaryloxy, (C5-C10)ar(C1-C6)alkyl or (C5-C10)heteroar(C1-C6)alkyl, (C5-C10)ar(C1-C6)alkoxy or (C5-C10)heteroar(C1-C6)alkoxy, HO—(C═O)—, ester, amido, ether, amino, amino(C1-C6)alkyl, (C1-C6)alkylamino(C1-C6)alkyl, di(C1-C6)alkylamino(C1-C6)alkyl, (C5-C10)heterocyclyl(C1-C6)alkyl, (C1-C6)alkyl- and di(C1-C6)alkylamino, cyano, nitro, carbamoyl, (C1-C6)alkylcarbonyl, (C1-C6)alkoxycarbonyl, (C1-C6)alkylaminocarbonyl, di(C1-C6)alkylaminocarbonyl, (C5-C10)arylcarbonyl, (C5-C10)aryloxycarbonyl, (C1-C6)alkylsulfonyl, and (C5-C10)arylsulfonyl;
• each R3 is independently selected from the group consisting of:
• hydrogen, halo, halo(C1-C6)alkyl, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, perhalo(C1-C6)alkyl, phenyl, (C5-C10)heteroaryl, (C5-C10)heterocyclic, (C3-C10)cycloalkyl, hydroxy, (C1-C6)alkoxy, perhalo(C1-C6)alkoxy, phenoxy, (C5-C10)heteroaryl-O—, (C5-C10)heterocyclic-O—, (C3-C10)cycloalkyl-O—, (C1-C6)alkyl-S—, (C1-C6)alkyl-SO2—, (C1-C6)alkyl-NH—SO2—, O2N—, NC—, amino, Ph(CH2)1-6HN—, (C1-C6)alkyl HN—, (C1-C6)alkylamino, [(C1-C6)alkyl]2-amino, (C1-C6)alkyl-SO2—NH—, amino(C═O)—, aminoO2S—, (C1-C6)alkyl-(C═O)—NH—, (C1-C6)alkyl-(C═O)—[(((C1-C6)alkyl)-N]—, phenyl-(C═O)—NH—, phenyl-(C═O)—[((C1-C6)alkyl)-N]—, (C1-C6)alkyl-(C═O)—, phenyl-(C═O)—, (C5-C10)heteroaryl-(C═O)—, (C5-C10)heterocyclic-(C═O)—, (C3-C10)cycloalkyl-(C═O)—, HO—(C═O)—, (C1-C6)alkyl-O—(C═O)—, H2N(C═O)—, (C1-C6)alkyl-NH—(C═O)—, [(C1-C6)alkyl]2—N—(C═O)—, phenyl-NH—(C═O)—, phenyl-[((C1-C6)alkyl)-N]—(C═O)—, (C5-C10)heteroaryl-NH—(C═O)—, (C5-C10)heterocyclic-NH—(C═O)—, (C3-C10)cycloalkyl-NH—(C═O)— and (C1-C6)alkyl-(C═O)—O—;
• where alkyl, alkenyl, alkynyl, phenyl, heteroaryl, heterocyclic, cycloalkyl, alkoxy, phenoxy, amino of R3 is optionally substituted by at least one substituent independently selected from (C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkyl, halo, H2N—, Ph(CH2)1-6HN—, and (C1-C6)alkylHN—;
• s is an integer from one to five;
• and
• R6 is selected from the group consisting of hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, phenyl, (C5-C10)heteroaryl, (C5-C10)heterocyclic, (C3-C10)cycloalkyl, (C1-C6)alkyl-(SO2)—, phenyl-(SO2)—, H2N—(SO2)—, (C1-C6)alkyl-NH—(SO2)—, ((C1-C6)alkyl)2N—(SO2)—, phenyl-NH—(SO2)—, (phenyl)2N—(SO2)—, (C1-C6)alkyl-(C═O)—, phenyl-(C═O)—, (C5-C10)heteroaryl-(C═O)—, (C5-C10)heterocyclic-(C═O)—, (C3-C10)cycloalkyl-(C═O)—, (C1-C6)alkyl-O—(C═O)—, (C5-C10)heterocyclic-O—(C═O)—, (C3-C10)cycloalkyl-O—(C═O)—, H2N—(C═O)—, (C1-C6)alkyl-NH—(C═O)—, phenyl-NH—(C═O)—, (C5-C10)heteroaryl-NH—(C═O)—, (C5-C10)heterocyclic-NH—(C═O)—, (C3-C10)cycloalkyl-NH—(C═O)—, ((C1-C6)alkyl)2N—(C═O)—, (phenyl)2N—(C═O)—, phenyl-[((C1-C6)alkyl)-N]—(C═O)—, (C5-C10)heteroaryl-[((C1-C6)alkyl)-N]—(C═O)—, (C5-C10)heterocyclic-[((C1-C6)alkyl)-N]—(C═O)—, and (C3-C10)cycloalkyl-[((C1-C6)alkyl)-N]—(C═O)—;
• where alkyl, alkenyl, alkynyl, phenyl, benzyl, heteroaryl, heterocyclic, cycloalkyl, alkoxy, phenoxy, amino of R6 is optionally substituted with at least one moiety independently selected from the group consisting of halo, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, perhalo(C1-C6)alkyl, (C3-C10)cycloalkyl, phenyl, benzyl, (C5-C10)heterocyclic, (C5-C10)heteroaryl, (C1-C6)alkyl-SO2—, formyl, NC—, (C1-C6)alkyl-(C═O)—, (C3C 10)cycloalkyl-(C═O)—, phenyl-(C═O)—, (C5-C10)heterocyclic-(C═O)—, (C5-C10)heteroaryl-(C═O)—, HO—(C═O)—, (C1-C6)alkyl-O—(C═O)—, (C3-C10)cycloalkyl-O—(C═O)—, (C5-C10)heterocyclic-O—(C═O)—, (C1-C6)alkyl-NH—(C═O)—, (C3-C10)cycloalkyl-NH—(C═O)—, phenyl-NH—(C═O)—, (C5-C10)heterocyclic-NH—(C═O)—, (C5-C10)heteroaryl-NH—(C═O)—, ((C1-C6)alkyl)2—N—(C═O)—, phenyl-[((C1-C6)alkyl)-N]—(C═O)—, hydroxy, (C1-C6)alkoxy, perhalo(C1-C6)alkoxy, (C3-C10)cycloalkyl-O—, phenoxy, (C5-C10)heterocyclic-O—, (C5-C10)heteroaryl-O—, (C1-C6)alkyl-(C═O)—O—, (C3-C10)cycloalkyl-(C═O)—O—, phenyl-(C═O)—O—, (C5-C10)heterocyclic-(C═O)—O—, (C5-C10)heteroaryl-(C═O)—O—, O2N—, amino, (C1-C6)alkylamino, ((C1-C6)alkyl)2-amino, formamidyl, (C1-C6)alkyl-(C═O)—NH—, (C3-C10)cycloalkyl-(C═O)—NH—, phenyl-(C═O)—NH—, (C5-C10)heterocyclic-(C═O)—NH—, (C5-C10)heteroaryl-(C═O)—NH—, (C1-C6)alkyl-(C═O)—[((C1-C6)alkyl)-N]—, phenyl-(C═O)—[(C1-C6)alkyl-N]—, (C1-C6)alkyl-SO2NH—, (C3-C10)cycloalkyl-SO2NH—, phenyl-SO2NH—, (C5-C10)heterocyclic-SO2NH— and (C5-C10)heteroaryl-SO2NH—;
• wherein the phenyl or heteroaryl moiety of a R6 substituent is optionally further substituted with at least one radical independently selected from the group consisting of halo, (C1-C6)alkyl, (C1-C6)alkoxy, perfluoro(C1-C6)alkyl and perfluoro(C1-C6)alkoxy,
• with the proviso that R1 is not a naphthyl or phenyl;
• and
• with the proviso that when R1 is a phenyl fused with an aromatic or non-aromatic cyclic ring of 5-7 members containing up to three N atoms, said N is other than —NH or —NC1-6alkyl or if said N is —NH or —NC1-6alkyl, then R1 must be further substituted;
• and
• with the proviso that when R1 is a phenyl fused with an aromatic or non-aromatic cyclic ring of 5-7 members containing 1-3 heteroatoms independently selected from O and S, then R1 must be further substituted.