253308-55-3Relevant academic research and scientific papers
PTP1B inhibitors: Synthesis and evaluation of difluoro-methylenephosphonate bioisosteres on a sulfonamide scaffold
Holmes, Christopher P.,Li, Xianfeng,Pan, Yijun,Xu, Caiding,Bhandari, Ashok,Moody, Claire M.,Miguel, Joy A.,Ferla, Steven W.,De Francisco, M. Nuria,Frederick, Brian T.,Zhou, Siqun,Macher, Natalie,Jang, Larry,Irvine, Jennifer D.,Grove, J. Russell
, p. 2719 - 2724 (2008)
We have synthesized and evaluated a series of triaryl sulfonamide-based PTP1B inhibitors in which a difluoro-methylenephosphonate group of a potent lead has been replaced by potential bioisosteric replacements. Several mono- or di-charged compounds (8a, 8b, and 15a) were shown exhibit inhibitory activity in the low micromolar range, demonstrating the feasibility of using this approach in identifying non-phosphonate pTyr mimetics in a small molecular scaffold. These results also provide a useful indication of the relative effectiveness of these pTyr mimetics.
Discovery and structure-activity relationships of novel sulfonamides as potent PTP1B inhibitors
Holmes, Christopher P.,Li, Xianfeng,Pan, Yijun,Xu, Caiding,Bhandari, Ashok,Moody, Claire M.,Miguel, Joy A.,Ferla, Steven W.,De Francisco, M. Nuria,Frederick, Brian T.,Zhou, Siqun,Macher, Natalie,Jang, Larry,Irvine, Jennifer D.,Grove, J. Russell
, p. 4336 - 4341 (2007/10/03)
A series of novel sulfonamides containing a single difluoromethylene- phosphonate group were discovered to be potent inhibitors of protein tyrosine phosphatase 1B. Structure-activity relationships around the scaffold were investigated, leading to the identification of compounds with IC50 or Ki values in the low nanomolar range. These sulfonamide-based inhibitors exhibit 100 and 30 times higher inhibitory activity than the corresponding tertiary amines and carboxamides, respectively.
