Design of Novel Thiazole Bearing Pyrazole Derivatives and Their Dual Activities as ACE Inhibitors and Calcium Channel Blockers in Cardiovascular Disease

作者：Jiang, Cheng; Yuan, Zhi; Wang, Ju-Fei; Fu, Jie; Jiang, Guang-Jun; Zheng, Liang-Rong^*

来源：Latin American Journal of Pharmacy, 2016, 35(3): 440-449.

• angiotensin converting enzyme inhibitors
• hypertension
• synthesis
• thiazole
• vasorelaxation

In an attempt to develop drugs for cardio-vascular disease, present manuscript deal with the development of dual acting agents targeting angiotensin converting enzyme (ACE) and calcium channel to treat hypertension. These molecules were developed via efficient multi-step synthetic route in excellent yield. In ACE inhibitors assay, these compounds showed considerable percentage of inhibition (32-94 %) with IC50 = 1.2 and 1.5 mu M for most promising compound 6e and 6o, respectively. In molecular docking study with ACE, compound 6e revealed similar fashion of molecular interaction with catalytic residues His353, Ala 354, Tyr 523, Tyr 520, and Glu 152, comparable with standard lisinopril. Additionally, in rat aortic strip model, these molecules significantly induce vasorelaxaticin via inhibiting Ca2+ channel in dose dependent manner.

• 出版日期2016-4
• 单位浙江大学