Palacios, Daniel, Meredith, Erik, Kawanami, Toshio, Chen, Xin, Darsigny, Veronique, Geno, Erin, Palermo, Mark, Guy, Chantale, Hewett, Jeffrey, Tierney, Laryssa, Thigale, Sachin, Weihofen, Wilhelm, Argikar, Upendra, Boynton, Geoffrey, George, Elizabeth, Wang, Louis, Adams, Christopher, Baird, Daniel and Busby, Scott (2017) Structure based design of Nicotinamide phosphoribosyltransferase (NAMPT) inhibitors from a phenotypic screen. ACS medicinal chemistry letters.

Abstract

ABSTRACT: Utilizing publicly available crystal structures of NAMPT and in silico docking of our internal compound library a NAMPT inhibitor obtained from a phenotypic screening effort was replaced with a more synthetically tractable scaffold. This compound then provided an excellent foundation for further optimization using crystallography driven structure based drug design. From this approach, two key motifs were identified, the (S, S) cyclopropyl carboxamide and the (S) methyl benzyl amine that endowed compounds with excellent cell based potency. As exemplified by compound 27e such compounds could be useful tools to explore NAMPT biology in vivo.

Item Type:	Article
Date Deposited:	22 Feb 2017 00:45
Last Modified:	22 Feb 2017 00:45
URI:	https://oak.novartis.com/id/eprint/30638