2-Phenyl and 2-heterocyclic-4-(3-(pyridin-2-yl)-1H-pyrazol-4-yl)pyridines as inhibitors of TGF-β1 and activin A signalling.

Abstract Novel inhibitors of TGF-β1 and activin A signalling based on a 2-aryl-4-(3-(pyridin-2-yl)-1 H -pyrazol-4-yl)pyridine pharmacophore have been synthesised. Compounds containing phenyl or aromatic nitrogen heterocycle substituents inhibited both types of signalling with HEK-293T cells in culture, with a selectivity preference for TGF-β1. Synthetic compounds containing pyridin-3-yl, pyrazol-4-yl, pyrazol-1-yl or 1 H -imidazoyl-1-yl substituents exhibited structural and functional attributes suitable for further investigation related to the development of more potent TGF-β inhibitors.