The Design, Synthesis and Evaluation of Rho-kinase Inhibitory Activity of 4-aryl-thiazole-2-amines

• Published in: Iranian journal of pharmaceutical research : IJPR Vol. 20; no. 3; pp. 121 - 131
• Main Authors: Wang, Linan, Ouyang, Ben, Fan, Meixia, Qi, Junhui, Yao, Lei
• Format: Journal Article
• Language: English
• Published: Iran Shaheed Beheshti University of Medical Sciences 2021
• Subjects: Original; Inhibitors; ROCK; Synthesis; 4-aryl-thiazole-2-amine; Kinase
• ISSN: 1735-0328; 1726-6890
• DOI: 10.22037/ijpr.2020.114468.14866

Rho-associated kinases (ROCK) are a class of serine/threonine kinases that play important roles in various biological processes. ROCK are becoming attractive targets for drug designing. A novel scaffold was designed according to molecular hybridization strategy, then a series of 4-aryl-5-aminomethyl-thiazole-2-amines were synthesized, and their inhibitory activities on ROCK were screened by enzyme-linked immunosorbent assay (ELISA). The results showed that 4-aryl-5-aminomethyl-thiazole-2-amines derivatives displayed certain ROCK II inhibitory activities. The IC value of the most potent compound 4v was found to be 20 nM. The preliminary structure-activity-relationship investigation showed that compounds with 4-pyridine substitution were generally found to be more potent than compounds with 3-pyridine substitution. The molecular docking studies indicated that more optimization work needs to conduct to obtain more potent ROCK inhibitors.