107623-36-9Relevant academic research and scientific papers
CYCLOPROPYL AMIDE DERIVATIVES
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, (2014/05/24)
The present invention relates to certain cyclopropyl amide compounds, pharmaceutical compositions comprising such compounds, and methods of treating cancer, including leukemias and solid tumors, inflammatory diseases, osteoporosis, atherosclerosis, irritable bowel syndrome, and other diseases and medical conditions, with such compounds and pharmaceutical compositions. The present invention also relates to certain cyclopropyl amide compounds for use in inhibiting nicotinamide phosphoribosyltransferase ("NAMPT").
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.
