Two series of nitrogenous heterocycle compounds--1,2,4-trisubstituted imidazoles and 1,3,5-trisubstituted pyrazoles have been synthesized and evaluated for their ALK5 inhibitory activity and cytotoxicity in TGFbeta-Smad2 assay and MTT assay, respectively. The ALK4/5/7 inhibitory activity of some compound was also evaluated in ALK4/5/7 autophosphorylation assays. Compounds 6c and 14c showed relatively potent ALK5 inhibition while weak cytotoxicity. At the same time, compounds 6c and 14c display relatively better ALK5 selectivity versus ALK4/ALK7 (nearly 10-fold) compared with SB431542, a well known ALK5 inhibitor. Compound 6g2 proved to be a moderately selective ALK4 inhibitor versus ALK5 and ALK7 (>10-fold). The binding mode of 14c generated by flexible docking study shows that 14c fits well into the site cavity of ALK5 by forming several tight interactions.