title: Inhibition of noroviruses by piperazine derivatives.
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.
authors: Department of Chemistry, Wichita State University, Wichita, KS 67260, USA.
authors: Dengfeng
authors: D
authors: Dou
authors: Guijia
authors: G
authors: He
authors: Sivakoteswara Rao
authors: SR
authors: Mandadapu
authors: Sridhar
authors: S
authors: Aravapalli
authors: Yunjeong
authors: Y
authors: Kim
authors: Kyeong-Ok
authors: KO
authors: Chang
authors: William C
authors: WC
authors: Groutas
mesh_terms: D020816:Amino Acid Motifs; D000998:Antiviral Agents / Q000494:pharmacology*; D017250:Caliciviridae Infections / Q000188:drug therapy*; D002460:Cell Line; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D006801:Humans; D008956:Models, Chemical; D029322:Norovirus / Q000187:drug effects / Q000378:metabolism*; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D010879:Piperazines