851634-64-5Relevant academic research and scientific papers
Structure-Based Design of N-(5-Phenylthiazol-2-yl)acrylamides as Novel and Potent Glutathione S-Transferase Omega 1 Inhibitors
Dai, Weiyang,Samanta, Soma,Xue, Ding,Petrunak, Elyse M.,Stuckey, Jeanne A.,Han, Yanyan,Sun, Duxin,Wu, Yong,Neamati, Nouri
, p. 3068 - 3087 (2019/03/07)
Using reported glutathione S-transferase omega 1 (GSTO1-1) cocrystal structures, we designed and synthesized acrylamide-containing compounds that covalently bind to Cys32 on the catalytic site. Starting from a thiazole derivative 10 (GSTO1-1 IC50 = 0.6 μM), compound 18 was synthesized and cocrystallized with GSTO1. Modification on the amide moiety of hit compound 10 significantly increased the GSTO1-1 inhibitory potency. We solved the cocrystal structures of new derivatives, 37 and 44, bearing an amide side chain bound to GSTO1. These new structures showed a reorientation of the phenyl thiazole core of inhibitors, 37 and 44, when compared to 18. Guided by the cocrystal structure of GSTO1:44, analogue 49 was designed, resulting in the most potent GSTO1-1 inhibitor (IC50 = 0.22 ± 0.02 nM) known to date. We believe that our data will form the basis for future studies of developing GSTO1-1 as a new drug target for cancer therapy.
NOVEL PYRROLE DERIVATIVE HAVING UREIDE GROUP AND AMINOCARBONYL GROUP AS SUBSTITUENTS
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Page/Page column 23, (2009/12/05)
Objects of the present invention are to study on the synthesis of a novel pyrrole derivative having a ureido group and an aminocarbonyl group as substituents or a salt thereof, to find a pharmacological effect of the derivative or a salt thereof, and to f
Novel 5-HT2A receptor ligands
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Page/Page column 14, (2010/02/11)
Compounds of formula I: are antagonists of the human 5-HT2A receptor, and hence useful in treatment or prevention of a variety of neurological conditions.
