Discovery of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1: optimization of kinase selectivity and pharmacokinetics.
Basic Information
ID: ALA2407065
Journal: Bioorg Med Chem Lett
Title: Discovery of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1: optimization of kinase selectivity and pharmacokinetics.
Authors: Hornberger KR, Chen X, Crew AP, Kleinberg A, Ma L, Mulvihill MJ, Wang J, Wilde VL, Albertella M, Bittner M, Cooke A, Kadhim S, Kahler J, Maresca P, May E, Meyn P, Romashko D, Tokar B, Turton R.
Abstract: The kinase selectivity and pharmacokinetic optimization of a series of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1 is described. The intersection of insights from molecular modeling, computational prediction of metabolic sites, and in vitro metabolite identification studies resulted in a simple and unique solution to both of these problems. These efforts culminated in the discovery of compound 13a, a potent, relatively selective inhibitor of TAK1 with good pharmacokinetic properties in mice, which was active in an in vivo model of ovarian cancer.
CiteXplore: 23856049
DOI: 10.1016/j.bmcl.2013.06.054
Patent ID: ┄