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

ABSTRACT: 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 IC50 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.

SUBMITTER: Wang L

PROVIDER: S-EPMC8653655 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Wang Linan L Ouyang Ben B Fan Meixia M Qi Junhui J Yao Lei L

Iranian journal of pharmaceutical research : IJPR 20210101 3

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 ...[more]

PMID: 34903975

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