1365643-24-8Relevant articles and documents
Discovery of INT131: A selective PPARγ modulator that enhances insulin sensitivity
Taygerly, Joshua P.,McGee, Lawrence R.,Rubenstein, Steven M.,Houze, Jonathan B.,Cushing, Timothy D.,Li, Yang,Motani, Alykhan,Chen, Jin-Long,Frankmoelle, Walter,Ye, Guosen,Learned, Marc R.,Jaen, Juan,Miao, Shichang,Timmermans, Pieter B.,Thoolen, Martin,Kearney, Patrick,Flygare, John,Beckmann, Holger,Weiszmann, Jennifer,Lindstrom, Michelle,Walker, Nigel,Liu, Jinsong,Biermann, Donna,Wang, Zhulun,Hagiwara, Atsushi,Iida, Tetsuya,Aramaki, Hisateru,Kitao, Yuki,Shinkai, Hisashi,Furukawa, Noboru,Nishiu, Jun,Nakamura, Motonao
, p. 979 - 992 (2013)
PPARγ is a member of the nuclear hormone receptor family and plays a key role in the regulation of glucose homeostasis. This Letter describes the discovery of a novel chemical class of diarylsulfonamide partial agonists that act as selective PPARγ modulators (SPPARγMs) and display a unique pharmacological profile compared to the thiazolidinedione (TZD) class of PPARγ full agonists. Herein we report the initial discovery of partial agonist 4 and the structure-activity relationship studies that led to the selection of clinical compound INT131 (3), a potent PPARγ partial agonist that displays robust glucose-lowering activity in rodent models of diabetes while exhibiting a reduced side-effects profile compared to marketed TZDs.
Salicylanilide Analog Minimizes Relapse of Clostridioides difficile Infection in Mice
Blake, Steven,Thanissery, Rajani,Rivera, Alissa J.,Hixon, Mark S.,Lin, Mingliang,Theriot, Casey M.,Janda, Kim D.
supporting information, p. 6898 - 6908 (2020/07/28)
Clostridioides difficile infection (CDI) causes serious and sometimes fatal symptoms like diarrhea and pseudomembranous colitis. Although antibiotics for CDI exist, they are either expensive or cause recurrence of the infection due to their altering the colonic microbiota, which is necessary to suppress the infection. Here, we leverage a class of known membrane-targeting compounds that we previously showed to have broad inhibitory activity across multiple Clostridioides difficile strains while preserving the microbiome to develop an efficacious agent. A new series of salicylanilides was synthesized, and the most potent analog was selected through an in vitro inhibitory assay to evaluate its pharmacokinetic parameters and potency in a CDI mouse model. The results revealed reduced recurrence of CDI and diminished disturbance of the microbiota in mice compared to standard-of-care vancomycin, thus paving the way for novel therapy that can potentially target the cell membrane of C. difficile to minimize relapse in the recovering patient.
NOVEL POLYAMIDEIMIDE HAVING LOW THERMAL EXPANSION COEFFICIENT
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Paragraph 0119; 0120; 0121; 0122, (2015/11/24)
The present invention relates to a polyamideimide comprising an asymmetric dicarboxylic acid derivative wherein, from among a cyclic group A and a cyclic group B, two substitutents groups R and R' are bonded only to the cyclic group A on one side. A polym
