1365643-24-8Relevant academic research and scientific papers
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.
Salicylanilides Reduce SARS-CoV-2 Replication and Suppress Induction of Inflammatory Cytokines in a Rodent Model
Beutler, Nathan,Blake, Steven,Eubanks, Lisa M.,Janda, Kim D.,Ji, Henry,Manning, John T.,Maruyama, Junki,Paessler, Slobodan,Shaabani, Namir,Teijaro, John R.
, p. 2229 - 2237 (2021/08/24)
SARS-CoV-2 virus has recently given rise to the current COVID-19 pandemic where infected individuals can range from being asymptomatic, yet highly contagious, to dying from acute respiratory distress syndrome. Although the world has mobilized to create antiviral vaccines and therapeutics to combat the scourge, their long-term efficacy remains in question especially with the emergence of new variants. In this work, we exploit a class of compounds that has previously shown success against various viruses. A salicylanilide library was first screened in a SARS-CoV-2 activity assay in Vero cells. The most efficacious derivative was further evaluated in a prophylactic mouse model of SARS-CoV-2 infection unveiling a salicylanilide that can reduce viral loads, modulate key cytokines, and mitigate severe weight loss involved in COVID-19 infections. The combination of anti-SARS-CoV-2 activity, cytokine inhibitory activity, and a previously established favorable pharmacokinetic profile for the lead salicylanilide renders salicylanilides in general as promising therapeutics for COVID-19.
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.
Asymmetric Diamine Compounds Containing Two Functional Groups and Polymers Therefrom
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Paragraph 0102; 0103; 0104; 0105, (2015/02/25)
The present invention relates to a novel diamine compound, wherein two substituents R and R′ are introduced asymmetrically, and a polymer thereof. The polymer may have excellent solubility in the organic solvent and allows for easy processibility after im
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
Discovery of novel 2-hydroxydiarylamide derivatives as TMPRSS4 inhibitors
Kang, Sunghyun,Min, Hye-Jin,Kang, Min-Seo,Jung, Myung-Geun,Kim, Semi
, p. 1748 - 1751 (2013/04/10)
TMPRSS4 is a novel type II transmembrane serine protease that has been implicated in the invasion and metastasis of colon cancer cells. In this study, a novel series of 2-hydroxydiarylamide derivatives were synthesized and evaluated for inhibiting TMPRSS4 serine protease activity and suppressing cancer cell invasion. These derivatives demonstrated good inhibitory activity against TMPRSS4 serine protease, which correlated with the promising anti-invasive activity of colon cancer cells overexpressing TMPRSS4.
Poly(arylene ether)s with low refractive indices: Poly(biphenylene oxide)s with trifluoromethyl pendant groups via a meta-activated nitro displacement Reaction
Kim, Sun Dal,Ka, Duyoun,Chung, Im Sik,Kim, Sang Youl
experimental part, p. 3023 - 3031 (2012/06/30)
High-molecular-weight poly(biphenylene oxide)s (PBPO) were prepared from AB-type monomers, 4′(3′)-hydroxy-4-nitro-2,6-bis(trifluoromethyl) biphenyl, through a meta-activated nitro displacement reaction. The displacement of nitro leaving group activated by
