首页 | 本学科首页   官方微博 | 高级检索  
     


Synthesis and pharmacological study of Rho-kinase inhibitors: pharmacomodulations on the lead compound Fasudil
Authors:Logé Cédric  Siomboing Xavier  Wallez Valérie  Scalbert Elizabeth  Bennejean Caroline  Cario-Tourmaniantz Christelle  Loirand Gervaise  Gressier Bernard  Pacaud Pierre  Luyckx Michel
Affiliation:Faculté des Sciences Pharmaceutiques et Biologiques, BP 83, 59006 Lille Cedex, France. cloge@phare.univ-lille2.fr
Abstract:
With a view to specifying structure-activity relationships we have synthesised a new series of analogues of the Rho-kinase inhibitor 1-(5-isoquinolinesulfonyl)-homopiperazine (Fasudil). The structural modifications concerned the isoquinolinyl heterocycle and the sulfonyl group which are the two main features of this lead compound. These analogues were evaluated on the actin cytoskeleton and on the enzymatic activity of Rho-kinase. Most of the chemical modifications result in a loss of activity showing that interactions of Fasudil with the catalytic domain of Rho-kinase seem to be particularly definite and sensitive to structural variations. The presence of an isoquinolinyl nitrogen and a basic amino group separated by a spacer bearing a sulfonamide function are of utmost importance. Only the tetra-hydroisoquinoline analogue 3 shows the same activity as Fasudil. Moreover, this compound is unable to inhibit PKC biological activity contrary to Fasudil. The loss of the aromatic property could increase the selectivity level in favour of compound 3.
Keywords:
本文献已被 PubMed 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号