94341-56-7Relevant academic research and scientific papers
Discovery of potent and efficacious cyanoguanidine-containing nicotinamide phosphoribosyltransferase (Nampt) inhibitors
Zheng, Xiaozhang,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,Wang, Yunli,Yuen, Po-Wai,Bair, Kenneth W.
, p. 337 - 343 (2014/01/17)
A co-crystal structure of amide-containing compound (4) in complex with the nicotinamide phosphoribosyltransferase (Nampt) protein and molecular modeling were utilized to design and discover a potent novel cyanoguanidine-containing inhibitor bearing a sulfone moiety (5, Nampt Biochemical IC50 = 2.5 nM, A2780 cell proliferation IC50 = 9.7 nM). Further SAR exploration identified several additional cyanoguanidine-containing compounds with high potency and good microsomal stability. Among these, compound 15 was selected for in vivo profiling and demonstrated good oral exposure in mice. It also exhibited excellent in vivo antitumor efficacy when dosed orally in an A2780 ovarian tumor xenograft model. The co-crystal structure of this compound in complex with the NAMPT protein was also determined.
Discovery of potent and efficacious cyanoguanidine-containing nicotinamide phosphoribosyltransferase (Nampt) inhibitors
Zheng, Xiaozhang,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,Wang, Yunli,Yuen, Po-Wai,Bair, Kenneth W.
, p. 337 - 343 (2015/03/18)
A co-crystal structure of amide-containing compound (4) in complex with the nicotinamide phosphoribosyltransferase (Nampt) protein and molecular modeling were utilized to design and discover a potent novel cyanoguanidine-containing inhibitor bearing a sulfone moiety (5, Nampt Biochemical IC50 = 2.5 nM, A2780 cell proliferation IC50 = 9.7 nM). Further SAR exploration identified several additional cyanoguanidine-containing compounds with high potency and good microsomal stability. Among these, compound 15 was selected for in vivo profiling and demonstrated good oral exposure in mice. It also exhibited excellent in vivo antitumor efficacy when dosed orally in an A2780 ovarian tumor xenograft model. The co-crystal structure of this compound in complex with the NAMPT protein was also determined.
Identification of 2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-derived ureas as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT)
Dragovich, Peter S.,Bair, Kenneth W.,Baumeister, Timm,Ho, Yen-Ching,Liederer, Bianca M.,Liu, Xiongcai,Liu, Yongbo,O'Brien, Thomas,Oeh, Jason,Sampath, Deepak,Skelton, Nicholas,Wang, Leslie,Wang, Weiru,Wu, Hongxing,Xiao, Yang,Yuen, Po-Wai,Zak, Mark,Zhang, Lei,Zheng, Xiaozhang
, p. 4875 - 4885 (2013/09/02)
Potent nicotinamide phosphoribosyltransferase (NAMPT) inhibitors containing 2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-derived ureas were identified using structure-based design techniques. The new compounds displayed improved aqueous solubilities, determined using a high-throughput solubility assessment, relative to previously disclosed urea and amide-containing NAMPT inhibitors. An optimized 2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-derived compound exhibited potent anti-NAMPT activity (18; BC NAMPT IC50 = 11 nM; PC-3 antiproliferative IC50 = 36 nM), satisfactory mouse PK properties, and was efficacious in a PC-3 mouse xenograft model. The crystal structure of another optimized compound (29; NAMPT IC50 = 10 nM; A2780 antiproliferative IC50 = 7 nM) in complex with the NAMPT protein was also determined.
AMIDO-BENZYL SULFONE AND SULFONAMIDE DERIVATIVES
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Page/Page column 74, (2013/09/12)
Disclosed are certain amido-benzyl sulfone and sulfonamide compounds, pharmaceutical compositions comprising such compounds, land methods of treatment using such compounds.
Identification of amides derived from 1H-pyrazolo[3,4-b]pyridine-5- carboxylic acid as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT)
Zheng, Xiaozhang,Bair, Kenneth W.,Bauer, Paul,Baumeister, Timm,Bowman, Krista K.,Buckmelter, Alexandre J.,Caligiuri, Maureen,Clodfelter, Karl H.,Feng, Yezhen,Han, Bingsong,Ho, Yen-Ching,Kley, Nikolai,Li, Hong,Liang, Xiaorong,Liederer, Bianca M.,Lin, Jian,Ly, Justin,O'Brien, Thomas,Oeh, Jason,Oh, Angela,Reynolds, Dominic J.,Sampath, Deepak,Sharma, Geeta,Skelton, Nicholas,Smith, Chase C.,Tremayne, Jarrod,Wang, Leslie,Wang, Weiru,Wang, Zhongguo,Wu, Hongxing,Wu, Jiansheng,Xiao, Yang,Yang, Guangxing,Yuen, Po-Wai,Zak, Mark,Dragovich, Peter S.
supporting information, p. 5488 - 5497 (2013/10/01)
Potent, 1H-pyrazolo[3,4-b]pyridine-containing inhibitors of the human nicotinamide phosphoribosyltransferase (NAMPT) enzyme were identified using structure-based design techniques. Many of these compounds exhibited nanomolar antiproliferation activities a
NOVEL COMPOUNDS AND COMPOSITIONS FOR THE INHIBITION OF NAMPT
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Page/Page column 391, (2012/03/26)
The present invention relates to compounds and compositions for the inhibition of NAMPT, their synthesis, applications and antidotes. An illustrative compound of the invention is shown below:
GUANIDINE COMPOUNDS AND COMPOSITIONS FOR THE INHIBITION OF NAMPT
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Page/Page column 80, (2012/03/26)
The present invention relates to compounds and compositions for the inhibition of NAMPT, their synthesis, applications and antidotes. An illustrative compound of the invention is shown below.
Substituted isothiazolones
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Page/Page column 25, (2010/11/25)
This invention is directed to a compound of Formula (I): and pharmaceutically acceptable forms thereof useful as inhibitors of cPLA2 and a method for preventing, treating or ameliorating a cPLA2 mediated inflammatory related disease, disorder or condition using a compound of Formula (I) and, more particularly, for preventing, treating or ameliorating a cPLA2 mediated inflammatory related disease, disorder or condition which results from the cellular secretion of TXB2 or LTB4.
Inhibitors of c-Jun N-terminal kinases
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Page/Page column 75, (2008/06/13)
The present invention relates to compounds that are inhibitors of c-jun N-terminal kinase 1, 2, or 3 (JNK1, JNK2, or JNK3), compositions containing the compounds and the use of the compounds in the prevention or treatment of disorders regulated by the activation of JNK1, JNK2 and JNK3.
A CHEMOSELECTIVE CONVERSION OF ALKYL AND ARYL AZIDES TO AMINES WITH SODIUM HYDROGENTELLURIDE
Suzuki, Hitomi,Takaoka, Koji
, p. 1733 - 1736 (2007/10/02)
By treatment with sodium hydrogentelluride in ethanol/ether at room temperature, alkyl and aryl azides are easily converted to the corresponding primary amines in good yields.
