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

被引：6

作者：

Elhady, Ahmed K. ^{[1
]}

Sigler, Sara C. ^{[2
]}

Noureldin, Nazih ^{[1
]}

Canzoneri, Joshua C. ^{[2
]}

Ahmed, Nermin S. ^{[1
]}

Piazza, Gary A. ^{[2
]}

Abadi, Ashraf H. ^{[1
]}

机构：

[1] German Univ Cairo, Fac Pharm & Biotechnol, Dept Pharmaceut Chem, Cairo 11835, Egypt

[2] Univ S Alabama, Mitchell Canc Inst, Drug Discovery Res Ctr, Dept Oncol Sci & Pharmacol, Mobile, AL 36608 USA

来源：

SCIENTIA PHARMACEUTICA | 2016年 / 84卷 / 03期

基金：

美国国家卫生研究院;

关键词：

Terahydro-beta-carboline; phosphodiesterase; 5; inhibitors; stereochemistry; structure-based design;

D O I：

10.3390/scipharm84030428

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：428 / 446

页数：19

共 17 条

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