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Sci. Pharm. 2016, 84(3), 428-446; doi:10.3390/scipharm84030428

Structure-Based Design of Novel Tetrahydro-Beta-Carboline Derivatives with a Hydrophilic Side Chain as Potential Phosphodiesterase Inhibitors

1
Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt
2
Department of Oncologic Sciences and Pharmacology, Drug Discovery Research Center, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36608, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Thomas Erker
Received: 17 July 2015 / Accepted: 26 September 2015 / Published: 26 September 2015
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Abstract

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 6R, 12aR 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 S configuration. View Full-Text
Keywords: Terahydro-beta-carboline; phosphodiesterase 5 inhibitors; stereochemistry; structure-based design Terahydro-beta-carboline; phosphodiesterase 5 inhibitors; stereochemistry; structure-based design
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MDPI and ACS Style

Elhady, A.K.; Sigler, S.C.; Noureldin, N.; Canzoneri, J.C.; Ahmed, N.S.; Piazza, G.A.; Abadi, A.H. Structure-Based Design of Novel Tetrahydro-Beta-Carboline Derivatives with a Hydrophilic Side Chain as Potential Phosphodiesterase Inhibitors. Sci. Pharm. 2016, 84, 428-446.

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