Optimization of 2-(1H-imidazo-2-yl)piperazines series of Trypanosoma brucei growth inhibitors as potential treatment for the second stage of HAT |
| |
| Institution: | 1. Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan;2. Matsumoto Yushi-Seiyaku Co., Ltd, 2-1-3, Shibukawa-cho, Yao-City, Osaka 581-0075, Japan;1. Department of Psychiatry, Columbia University Medical Center, New York, USA;2. Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, USA;3. Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, USA;4. Department of Pathology, Section on Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA;1. Department of Physics, Saint-Petersburg State University, Ulianovskaja 3, 198504 St.Petersburg, Russia;2. Faculty of Chemistry, University of Wroclaw, Joliot Curie 14, 50-383 Wroclaw, Poland;3. Department of Chemistry, University of Antwerp, Groenenborgelaan 171, B-2020 Antwerp, Belgium |
| |
| Abstract: | A previous publication from our laboratory reported the identification of a new class of 2-(1H-imidazo-2-yl)piperazines as potent T. brucei growth inhibitors as potential treatment for Human African Trypanosomiasis (HAT). This work describes the structure–activity relationship (SAR) around the hit compound 1, which led to the identification of the optimized compound 18, a single digit nanomolar inhibitor (EC50 7 nM), not cytotoxic and with optimal in vivo profile that made it a suitable candidate for efficacy studies in a mouse model mimicking the second stage of disease. |
| |
| Keywords: | Sleeping sickness Human African Trypanosomiasis (HAT) Antiparasitic |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
