54528-22-2Relevant academic research and scientific papers
Discovery of potent and efficacious urea-containing nicotinamide phosphoribosyltransferase (NAMPT) inhibitors with reduced CYP2C9 inhibition properties
Gunzner-Toste, Janet,Zhao, Guiling,Bauer, Paul,Baumeister, Timm,Buckmelter, Alexandre J.,Caligiuri, Maureen,Clodfelter, Karl H.,Fu, Bang,Han, Bingsong,Ho, Yen-Ching,Kley, Nikolai,Liang, Xiaorong,Liederer, Bianca M.,Lin, Jian,Mukadam, Sophie,O'Brien, Thomas,Oh, Angela,Reynolds, Dominic J.,Sharma, Geeta,Skelton, Nicholas,Smith, Chase C.,Sodhi, Jasleen,Wang, Weiru,Wang, Zhongguo,Xiao, Yang,Yuen, Po-Wai,Zak, Mark,Zhang, Lei,Zheng, Xiaozhang,Bair, Kenneth W.,Dragovich, Peter S.
, p. 3531 - 3538 (2013/07/28)
Potent, reversible inhibition of the cytochrome P450 CYP2C9 isoform was observed in a series of urea-containing nicotinamide phosphoribosyltransferase (NAMPT) inhibitors. This unwanted property was successfully removed from the described inhibitors throug
Structure-based identification of ureas as novel nicotinamide phosphoribosyltransferase (Nampt) inhibitors
Zheng, Xiaozhang,Bauer, Paul,Baumeister, Timm,Buckmelter, Alexandre J.,Caligiuri, Maureen,Clodfelter, Karl H.,Han, Bingsong,Ho, Yen-Ching,Kley, Nikolai,Lin, Jian,Reynolds, Dominic J.,Sharma, Geeta,Smith, Chase C.,Wang, Zhongguo,Dragovich, Peter S.,Oh, Angela,Wang, Weiru,Zak, Mark,Gunzner-Toste, Janet,Zhao, Guiling,Yuen, Po-Wai,Bair, Kenneth W.
, p. 4921 - 4937 (2013/07/26)
Nicotinamide phosphoribosyltransferase (Nampt) is a promising anticancer target. Virtual screening identified a thiourea analogue, compound 5, as a novel highly potent Nampt inhibitor. Guided by the cocrystal structure of 5, SAR exploration revealed that the corresponding urea compound 7 exhibited similar potency with an improved solubility profile. These studies also indicated that a 3-pyridyl group was the preferred substituent at one inhibitor terminus and also identified a urea moiety as the optimal linker to the remainder of the inhibitor structure. Further SAR optimization of the other inhibitor terminus ultimately yielded compound 50 as a urea-containing Nampt inhibitor which exhibited excellent biochemical and cellular potency (enzyme IC50 = 0.007 μM; A2780 IC50 = 0.032 μM). Compound 50 also showed excellent in vivo antitumor efficacy when dosed orally in an A2780 ovarian tumor xenograft model (TGI of 97% was observed on day 17).
4- { [ ( PYRIDIN- 3 - YL -METHYL) AMINOCARBONYL] AMINO} BENZENE - SULFONE DERIVATIVES AS NAMPT INHIBITORS FOR THERAPY OF DISEASES SUCH AS CANCER
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Page/Page column 230-231, (2012/03/26)
The present invention relates to compounds and compositions for the inhibition of NAMPT, their synthesis, applications and antidotes. An embodiment of the invention is the provision of a compound of Formula IIIA.
