Novel oxazole and thiazole compounds as transforming growth factor (TGF) inhibitors

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

• 55
• or a pharmaceutically acceptable salt, prodrug, hydrate, tautomer or solvate thereof, wherein:
• X is O or S;
• 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;
• R4 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)alkylHN—, (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 R4 is optionally substituted by at least one substituent independently selected from the group consisting of (C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkyl, halo, H2N—, Ph(CH2)1-6HN—, (C1-C6)alkylHN, (C5-C10)heteroaryl and (C5-C10)heterocyclyl;
• with the proviso that when R4 is a substituted phenyl moiety, then (a) R1 is not naphthyl, phenyl or anthracenyl and (b) if R1 is a phenyl fused with an aromatic or non-aromatic cyclic ring of 5-7 members wherein said cyclic ring optionally contains up to three heteroatoms independently selected from N, O and S, then the fused cyclic ring of said R1 moiety is substituted;
• with the proviso that when R4 is NH2 and X is S, then R1 is not an amino-substituted pyridyl or pyrimidinyl moiety;
• and
• with the provisio that when in formula (Ia) R4 is CH3 and X is S, R1 is not a 3,4-dimethoxy substituted phenyl moiety.