746630-00-2Relevant articles and documents
Design, Synthesis, and Structure-Activity Relationships of 1,2,3-Triazole Benzenesulfonamides as New Selective Leucine-Zipper and Sterile-α Motif Kinase (ZAK) Inhibitors
Yang, Jianzhang,Shibu, Marthandam Asokan,Kong, Lulu,Luo, Jinfeng,Badrealamkhan, Farheen,Huang, Yanhui,Tu, Zheng-Chao,Yun, Cai-Hong,Huang, Chih-Yang,Ding, Ke,Lu, Xiaoyun
, p. 2114 - 2130 (2020)
ZAK is a new promising target for discovery of drugs with activity against antihypertrophic cardiomyopathy (HCM). A series of 1,2,3-triazole benzenesulfonamides were designed and synthesized as selective ZAK inhibitors. One of these compounds, 6p binds tightly to ZAK protein (Kd = 8.0 nM) and potently suppresses the kinase function of ZAK with single-digit nM (IC50 = 4.0 nM) and exhibits excellent selectivity in a KINOMEscan screening platform against a panel of 403 wild-type kinases. This compound dose dependently blocks p38/GATA-4 and JNK/c-Jun signaling and demonstrates promising in vivo anti-HCM efficacy upon oral administration in a spontaneous hypertensive rat (SHR) model. Compound 6p may serve as a lead compound for new anti-HCM drug discovery.
ANTIPROLIFERATIVE 2-(SULFO-PHENYL)-AMINOTHIAZOLE DERIVATIVES
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Page 61-62, (2010/02/08)
Aminothiazole compounds substituted with sulfur-containing groups are represented by the Formula (I), and their pharmaceutically acceptable salts, prodrugs, active metabolites, and pharmaceutically acceptable salts of said metabolites are described. These agents modulate and/or inhibit the cell proliferation and activity of protein kinases and are useful as pharmaceuticals for treating malignancies and other disorders.
