| Literature DB >> 27490827 |
Kimberly O Cameron1,2, Daniel W Kung1,2, Amit S Kalgutkar1,2, Ravi G Kurumbail1,2, Russell Miller1,2, Christopher T Salatto1,2, Jessica Ward1,2, Jane M Withka1,2, Samit K Bhattacharya1,2, Markus Boehm1,2, Kris A Borzilleri1,2, Janice A Brown1,2, Matthew Calabrese1,2, Nicole L Caspers1,2, Emily Cokorinos1,2, Edward L Conn1,2, Matthew S Dowling1,2, David J Edmonds1,2, Heather Eng1,2, Dilinie P Fernando1,2, Richard Frisbie1,2, David Hepworth1,2, James Landro1,2, Yuxia Mao1,2, Francis Rajamohan1,2, Allan R Reyes1,2, Colin R Rose1,2, Tim Ryder1,2, Andre Shavnya1,2, Aaron C Smith1,2, Meihua Tu1,2, Angela C Wolford1,2, Jun Xiao1,2.
Abstract
Adenosine monophosphate-activated protein kinase (AMPK) is a protein kinase involved in maintaining energy homeostasis within cells. On the basis of human genetic association data, AMPK activators were pursued for the treatment of diabetic nephropathy. Identification of an indazole amide high throughput screening (HTS) hit followed by truncation to its minimal pharmacophore provided an indazole acid lead compound. Optimization of the core and aryl appendage improved oral absorption and culminated in the identification of indole acid, PF-06409577 (7). Compound 7 was advanced to first-in-human trials for the treatment of diabetic nephropathy.Entities:
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Year: 2016 PMID： 27490827 DOI： 10.1021/acs.jmedchem.6b00866
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446