title: 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)-1H-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 1H-imidazoyl-1-yl substituents exhibited structural and functional attributes suitable for further investigation related to the development of more potent TGF-β inhibitors.
authors.affiliation: Centre for Green Chemistry, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Rudy
authors.initials: R
authors.lastname: Ciayadi
authors.forename: Mahesh
authors.initials: M
authors.lastname: Potdar
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Walton
authors.forename: Craig A
authors.initials: CA
authors.lastname: Harrison
authors.forename: Geoffrey F
authors.initials: GF
authors.lastname: Kelso
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Harris
authors.forename: Milton T W
authors.initials: MT
authors.lastname: Hearn
mesh_terms: D028341:Activins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D006571:Heterocyclic Compounds; D011725:Pyridines; D053773:Transforming Growth Factor beta1; C422405:activin A; D028341:Activins