title: MCR synthesis of praziquantel derivatives.
abstract: Schistosomiasis, a high volume neglected tropical disease affecting more than 200 million people worldwide, can only be effectively treated by the tetrahydroisoquinoline drug praziquantel (PZQ). Herein, we describe an efficient approach to access PZQ derivatives by the Ugi 4-component reaction followed by the Pictet-Spengler reaction in a two-step, one-pot procedure. 30 novel PZQ derivatives are described based on the Ugi 4-component reaction and an X-ray structure of a novel derivative revealing different conformation compared with PZQ is discussed. Several analogues comparable in activity to the drug PZQ have been identified based on an in vitro Schistosoma mansoni worm viability assay.
authors.affiliation: Department of Pharmaceutical Sciences, University of Pittsburgh, 3501 Fifth Avenue, BST3 11019, Pittsburgh, PA 1526, USA.
authors.forename: Haixia
authors.initials: H
authors.lastname: Liu
authors.forename: Samia
authors.initials: S
authors.lastname: William
authors.forename: Eberhardt
authors.initials: E
authors.lastname: Herdtweck
authors.forename: Sanaa
authors.initials: S
authors.lastname: Botros
authors.forename: Alexander
authors.initials: A
authors.lastname: Dömling
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic / Q000379:methods; D006224:Cricetinae / Q000469:parasitology; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D011223:Praziquantel / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D012550:Schistosoma mansoni / Q000187:drug effects*; D012552:Schistosomiasis / Q000188:drug therapy; D012555:Schistosomiasis mansoni / Q000188:drug therapy
chemical_list: D000871:Anthelmintics; D011223:Praziquantel