| Literature DB >> 25828863 |
Curt D Haffner1, J David Becherer1, Eric E Boros1, Rodolfo Cadilla1, Tiffany Carpenter1, David Cowan1, David N Deaton1, Yu Guo1, Wallace Harrington1, Brad R Henke1, Michael R Jeune1, Istvan Kaldor1, Naphtali Milliken1, Kim G Petrov1, Frank Preugschat1, Christie Schulte1, Barry G Shearer1, Todd Shearer1, Terrence L Smalley1, Eugene L Stewart1, J Darren Stuart1, John C Ulrich1.
Abstract
A series of thiazoloquin(az)olinones were synthesized and found to have potent inhibitory activity against CD38. Several of these compounds were also shown to have good pharmacokinetic properties and demonstrated the ability to elevate NAD levels in plasma, liver, and muscle tissue. In particular, compound 78c was given to diet induced obese (DIO) C57Bl6 mice, elevating NAD > 5-fold in liver and >1.2-fold in muscle versus control animals at a 2 h time point. The compounds described herein possess the most potent CD38 inhibitory activity of any small molecules described in the literature to date. The inhibitors should allow for a more detailed assessment of how NAD elevation via CD38 inhibition affects physiology in NAD deficient states.Entities:
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Year: 2015 PMID： 25828863 DOI： 10.1021/jm502009h
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446