Pyrazole compounds as transforming growth factor (TGF) inhibitors

A compound of formula (Ia):

• or a pharmaceutically acceptable salt, tautomer thereof, wherein R1 is
• wherein R2a is independently selected from the group consisting of:
• (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, C3-C10)cycloalkyl, (C5-C10)aryl, (C1-C6)alkylaryl, amino, carbonyl, carboxyl, (C2-C6)acid, (C1-C6)ester, (C1-C6)alkoxy, nitro, halo, hydroxyl, (C1-C6)alkoxy(C1-C6)ester, and where (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C10)cycloalkyl, (C5-C10)aryl, amino, (C2-C6)acid, (C1-C6)ester, and (C1-C6)alkoxy of R2a is optionally substituted by 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, phenyl, (C3-C10)cycloalkyl, formyl, NC—, (C1-C6)alkyl-(C═O)—, phenyl-(C═O)—, HO—(C═O)—, (C1-C6)alkyl-O—(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)—, O2N—, amino, (C1-C6)alkylamino, ((C1-C6)alkyl)2-amino, (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[—, H2N—(C═O)—NH—, (C1-C6)alkyl-HN—(C═O)—NH—, ((C1-C6)alkyl)2N—(C═O)—NH—, (C1-C6)alkyl-HN—(C═O)—[((C1-C6)alkyl)-N]—, ((C1-C6)alkyl)2N—(C═O)—[(C1-C6)alkyl-N]—, phenyl-(C═O)—NH—, (phenyl)2N—(C═O)—NH—, phenyl-HN—(C═O)—[((C1-C6)alkyl)-N]—, (phenyl-)2N—(C═O)—[((C1-C6alkyl)-N]—, (C1-C6)alkyl-O—(C═O)—NH—, (C1-C6)alkyl-O—(C═O)—[((C1-C6)alkyl)-N]—, phenyl-O—(C═O)—NH—, phenyl-O—(C═O)—[(alkyl)-N]—, (C1-C6)alkyl-SO2NH—, phenyl-SO2NH—, (C1-C6)alkyl-SO2—, phenyl-SO2—, hydroxy, (C1-C6)alkoxy, perhalo(C1-C6)alkoxy, phenoxy, (C1-C6)alkyl-(C═O)—O—, (C1-C6)ester-(C1-C6)alkyl-O—, phenyl-(C═O)—O—, H2N—(C═O)—O—, (C1-C6)alkyl-HN—(C═O)—O—, ((C1-C6) alkyl)2N—(C═O)—O—, phenyl-HN—(C═O)—O—, and (phenyl)2N—(C═O)—O—;
• 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, (C3-C10)cycloalkyl, hydroxy, (C-C6)alkoxy, perhalo(C1-C6)alkoxy, phenoxy, (C3-C10)cycloalkyl-O—, (C1-C6)alkyl-S—, (C1-C6)alkyl-SO2—, (C1-C6)alkyl-NH—SO2—, O2N—, NC—, amino, Ph(CH2)1-66HN—, (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)—, (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)—, (C3-C10)cycloalkyl-NH—(C═O)— and (C1-C6)alkyl-(C═O)—O—;
• where alkyl, alkenyl, alkynyl, phenyl, 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 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, (C3-C10)cycloalkyl, hydroxy, (C1-C6)alkoxy, perhalo(C1-C6)alkoxy, phenoxy, (C3-C10)cycloalkyl-O—, (C1-C6)alkyl-S—, (C1-C6)alkyl-SO2—, (C1-C6)alkyl-NH—SO2—, O2N—, NC—, amino, Ph(CH2)1-6NH—, alkylNH—, (C1-C6)alkylamino, [(C1-C6)alkyl]2-amino, (C1-C6)alkyl-SO2—NH—, amino(C═O)—, aminoSO2—, (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)—, 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)—, (C3-C10)cycloalkyl-NH—(C═O)—and (C1-C6)alkyl-(C═O)—O—,
• where alkyl, alkenyl, alkynyl, phenyl, cycloalkyl, alkoxy, phenoxy, and 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)1-6—NH—, and (C1-C6)alkylNH—;
• and
• R6 is selected from the group consisting of hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, phenyl, (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)—, (C3-C10)cycloalkyl-(C═O)—, (C1-C6)alkyl-O—(C═O)—, (C═O)—, (C3-C10)cycloalkyl-O—(C═O)—, H2N—(C═O)—, (C1-C6)alkyl-NH—(C═O)—, phenyl-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)—, and (C3-C10)cycloalkyl-[((C1-C6)alkyl)-N]—(C═O)—;
• where alkyl, alkenyl, alkynyl, phenyl, benzyl, 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, (C1-C6)alkyl-SO2—, formyl, NC—, (C1-C6)alkyl-(C═O)—, (C3C10)cycloalkyl-(C═O)—, phenyl-(C═O)—, HO—(C═O)—, (C1-C6)alkyl-O—(C═O)—, (C3-C10 cycloalkyl-O—(C═O)—, (C1-C6)alkyl-NH—(C═O)—, (C3-C10)cycloalkyl-NH—(C═O)—, phenyl-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, (C1-C6)alkyl-(C═O)—O—, (C3-C10)cycloalkyl-(C═O)—O—, phenyl-(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—, (C1-C6)alkyl-(C═O)—[((C1-C6alkyl)-N]—, phenyl-(C═O)—[(C1-C6)alkyl-N]—, (C1-C6)alkyl-SO2NH—, (C3-C10)cycloalkyl-SO2NH—, phenyl-SO2NH—, wherein the phenyl 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.