| Structural highlights
Publication Abstract from PubMed
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.
Discovery of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1: Optimization of kinase selectivity and pharmacokinetics.,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 Bioorg Med Chem Lett. 2013 Aug 15;23(16):4511-6. doi: 10.1016/j.bmcl.2013.06.054., Epub 2013 Jun 27. PMID:23856049[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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. Discovery of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1: Optimization of kinase selectivity and pharmacokinetics. Bioorg Med Chem Lett. 2013 Aug 15;23(16):4511-6. doi: 10.1016/j.bmcl.2013.06.054., Epub 2013 Jun 27. PMID:23856049 doi:10.1016/j.bmcl.2013.06.054
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