Bioorganic & Medicinal Chemistry Letters 2012-01-01

Inhibition of noroviruses by piperazine derivatives.

Dengfeng Dou, Guijia He, Sivakoteswara Rao Mandadapu, Sridhar Aravapalli, Yunjeong Kim, Kyeong-Ok Chang, William C Groutas

Index: Bioorg. Med. Chem. Lett. 22(1) , 377-9, (2012)

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Abstract

There is currently an unmet need for the development of small-molecule therapeutics for norovirus infection. The piperazine scaffold, a privileged structure embodied in many pharmacological agents, was used to synthesize an array of structurally-diverse derivatives which were screened for anti-norovius activity in a cell-based replicon system. The studies described herein demonstrate for the first time that functionalized piperazine derivatives possess anti-norovirus activity. Furthermore, these studies have led to the identification of two promising compounds (6a and 9l) that can be used as a launching pad for the optimization of potency, cytotoxicity, and drug-like characteristics.Copyright © 2011 Elsevier Ltd. All rights reserved.