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MCR Synthesis of Praziquantel Derivatives
Author(s) -
Liu Haixia,
William Samia,
Herdtweck Eberhardt,
Botros Sanaa,
Dömling Alexander
Publication year - 2012
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2011.01288.x
Subject(s) - praziquantel , schistosoma mansoni , schistosomiasis , tropical disease , drug discovery , in vitro , combinatorial chemistry , drug , chemistry , schistosoma , stereochemistry , pharmacology , biology , medicine , biochemistry , disease , immunology , helminths
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.