Calcium Channel Antagonists Discovered by a Multidisciplinary Approach
详细信息 查看全文
- 作者：Emanuele Carosati ; Gabriele Cruciani ; Alberto Chiarini ; Roberta Budriesi ; Pierfranco Ioan ; Raffaella Spisani ; Domenico Spinelli ; Barbara Cosimelli ; Fabio Fusi ; Maria Frosini ; Rosanna Matucci ; Frances
- 刊名：Journal of Medicinal Chemistry
- 出版年：2006
- 出版时间：August 24, 2006
- 年：2006
- 卷：49
- 期：17
- 页码：5206 - 5216
- 全文大小：322K
- 年卷期：v.49,no.17(August 24, 2006)
- ISSN：1520-4804
文摘
A multidisciplinary project has led to the discovery of novel, structurally diverse, L-type calcium entryblockers (CEBs). The absolute configuration of a recently reported CEB has been determined by vibrationalcircular dichroism spectroscopy, to assign the stereospecificity of the ligand-channel interaction. Thereafter,a virtual screening procedure was performed with the aim of identifying novel chemotypes for CEBs, startingfrom a database of purchasable compounds; 340 000 molecules were screened in silico in order to prioritizestructures of interest for bioscreening. As a result, 20 compounds were tested in vitro, and functional andbinding assays revealed several hits with promising behavior as CEBs.