746630-00-2Relevant academic research and scientific papers
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.
Heterocyclic benzene sulfonamide compound and application thereof
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Paragraph 0349-0353, (2020/07/21)
The invention relates to a heterocyclic benzene sulfonamide compound with a structure as shown in a formula (I) which is described in the specification and an application of the heterocyclic benzene sulfonamide compound in preparation of a ZAK inhibitor. The heterocyclic benzene sulfonamide compound can be used for effectively and highly selectively inhibiting ZAK protein kinase and further regulating the activation of downstream JNK/SAPK, p38, ERK and other pathways. The compound can be used for preparing medicines for preventing and treating various diseases related to ZAK kinase, such as myocardial hypertrophy, myocardial fibrosis, angina pectoris, coronary heart disease, heart failure, myocardial infarction and inflammation, and has the characteristics of better pharmacokinetics, low toxicity and higher druggability.
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.
