1226786-03-3Relevant articles and documents
Discovery of novel n-substituted prolinamido indazoles as potent rho kinase inhibitors and vasorelaxation agents
Yao, Yangyang,Li, Renze,Liu, Xiaoyu,Yang, Feilong,Yang, Ying,Li, Xiaoyu,Shi, Xiang,Yuan, Tianyi,Fang, Lianhua,Du, Guanhua,Jiao, Xiaozhen,Xie, Ping
, (2017)
Inhibitors of Rho kinase (ROCK) have potential therapeutic applicability in a wide range of diseases, such as hypertension, stroke, asthma and glaucoma. In a previous article, we described the lead discovery of DL0805, a new ROCK I inhibitor, showing potent inhibitory activity (IC50 6.7 μM). Herein, we present the lead optimization of compound DL0805, resulting in the discovery of 24- and 39-fold more-active analogues 4a (IC50 0.27 μM) and 4b (IC50 0.17 μM), among other active analogues. Moreover, ex-vivo studies demonstrated that 4a and 4b exhibited comparable vasorelaxant activity to the approved drug fasudil in rat aortic rings. The research of a preliminary structure-activity relationship (SAR) indicated that the target compounds containing a β-proline moiety have improved activity against ROCK I relative to analogues bearing an β-proline moiety, and among the series of the derivatives with a β-proline-derived indazole scaffold, the inhibitory activity of the target compounds with a benzyl substituent is superior to those with a benzoyl substituent.
Pyrrolidines
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Page/Page column 36-37, (2010/06/11)
This invention relates to a class of pyrrolidine compounds of formula (I), and pharmaceutically acceptable derivatives thereof, to their use in medicine, to compositions containing them, and to processes for their preparation. It also relates to intermedi
