Elhady Ahmed K, Sigler Sara C, Noureldin Nazih, Canzoneri Joshua C, Ahmed Nermin S, Piazza Gary A, Abadi Ashraf H
Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt.
Department of Oncologic Sciences and Pharmacology, Drug Discovery Research Center, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36608, USA.
Sci Pharm. 2015 Sep 26;84(3):428-446. doi: 10.3390/scipharm84030428.
Tadalafil is a clinically approved phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction and pulmonary arterial hypertension. It contains two chiral carbons, and the marketed isomer is the , isomer with a methyl substituent on the terminal nitrogen of the piperazinedione ring. In this report, tadalafil analogues with an extended hydrophilic side chain on the piperazine nitrogen were designed to interact with particular hydrophilic residues in the binding pocket. This leads to analogues with moderate inhibitory activity on phosphodiesterase-5, even for isomers in which chiral carbons are of the configuration.
他达拉非是一种临床批准用于治疗勃起功能障碍和肺动脉高压的磷酸二酯酶-5抑制剂。它含有两个手性碳，上市的异构体是哌嗪二酮环末端氮上带有甲基取代基的（此处原文缺失具体构型描述）异构体。在本报告中，设计了在哌嗪氮上带有延长亲水性侧链的他达拉非类似物，以与结合口袋中的特定亲水性残基相互作用。这导致了对磷酸二酯酶-5具有中等抑制活性的类似物，即使对于手性碳为（此处原文缺失具体构型描述）构型的异构体也是如此。
