Structure-based de novo design and synthesis of aminothiazole-based p38 MAP kinase inhibitors

被引：7
作者：
Park, Hwangseo [1 ]
Lee, Soyoung [2 ,3 ]
Hong, Sungwoo [2 ,3 ]
机构：
[1] Sejong Univ, Dept Biosci & Biotechnol, Seoul 143747, South Korea
[2] Korea Adv Inst Sci & Technol, IBS, Ctr Catalyt Hydrocarbon Functionalizat, Taejon 305701, South Korea
[3] Korea Adv Inst Sci & Technol, Dept Chem, Taejon 305701, South Korea
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 18期
基金：
新加坡国家研究基金会;
关键词：
De novo design; Kinase; p38; MAPK; Inhibitor; Anti-inflammatory drugs; DISCOVERY; POTENT; IDENTIFICATION;
D O I：
10.1016/j.bmcl.2015.07.094
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
p38 mitogen-activated protein kinase (MAPK) is a promising target for the development of therapeutics for various immunological diseases. We designed and synthesized aminothiazole-based p38 MAPK inhibitors of with IC50 values ranging from 0.1 to 2 mu M by means of the structure-based de novo design of phenyl-(2-phenylamino-thiazol-5-yl)-methanone scaffold. Because these newly identified inhibitors were also screened for having desirable physicochemical properties as a drug candidate, they deserve consideration for further investigation as anti-inflammatory drugs. Structural features relevant to the stabilization of the newly identified inhibitors in the ATP-binding site of p38 MAPK are discussed in detail. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码：3784 / 3787
页数：4
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