1407972-35-3Relevant articles and documents
Fragment-based identification of amides derived from trans-2-(pyridin-3-yl) cyclopropanecarboxylic acid as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT)
Giannetti, Anthony M.,Zheng, Xiaozhang,Skelton, Nicholas J.,Wang, Weiru,Bravo, Brandon J.,Bair, Kenneth W.,Baumeister, Timm,Cheng, Eric,Crocker, Lisa,Feng, Yezhen,Gunzner-Toste, Janet,Ho, Yen-Ching,Hua, Rongbao,Liederer, Bianca M.,Liu, Yongbo,Ma, Xiaolei,O'Brien, Thomas,Oeh, Jason,Sampath, Deepak,Shen, Youming,Wang, Chengcheng,Wang, Leslie,Wu, Hongxing,Xiao, Yang,Yuen, Po-Wai,Zak, Mark,Zhao, Guiling,Zhao, Qiang,Dragovich, Peter S.
, p. 770 - 792 (2014/03/21)
Potent, trans-2-(pyridin-3-yl)cyclopropanecarboxamide-containing inhibitors of the human nicotinamide phosphoribosyltransferase (NAMPT) enzyme were identified using fragment-based screening and structure-based design techniques. Multiple crystal structures were obtained of initial fragment leads, and this structural information was utilized to improve the biochemical and cell-based potency of the associated molecules. Many of the optimized compounds exhibited nanomolar antiproliferative activities against human tumor lines in in vitro cell culture experiments. In a key example, a fragment lead (13, KD = 51 μM) was elaborated into a potent NAMPT inhibitor (39, NAMPT IC 50 = 0.0051 μM, A2780 cell culture IC50 = 0.000 49 μM) which demonstrated encouraging in vivo efficacy in an HT-1080 mouse xenograft tumor model.
NOVEL COMPOUNDS AND COMPOSITIONS FOR THE INHIBITION OF NAMPT
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Page/Page column 89-90, (2012/11/14)
The present invention relates to compounds and composition for inhibition of NAMPT, their synthesis, applications and antidotes. An illustrative compound of the invention is shown below.
