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Identification and development of the 1,4-benzodiazepin-2-one and quinazoline-2,4-dione scaffolds as submicromolar inhibitors of HAT

Clark, Rachel L. and Clements, Carol J. and Barrett, Michael P. and Mackay, Simon P. and Rathnam, Rajendra P. and Owusu-Dapaah, George and Spencer, John and Huggan, Judith K. (2012) Identification and development of the 1,4-benzodiazepin-2-one and quinazoline-2,4-dione scaffolds as submicromolar inhibitors of HAT. Bioorganic and Medicinal Chemistry, 20 (20). pp. 6019-6033. ISSN 0968-0896

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Abstract

A library of 1,4-benzodiazepines has been synthesised and evaluated for activity against Trypanosoma brucei, a causative parasite of Human African Trypanosomiasis (HAT). The most potent of these derivatives has an MIC value of 0.97 mu M. Herein we report the design, synthesis and biological evaluation of the abovementioned compounds. (C) 2012 Elsevier Ltd. All rights reserved.