Catechol pyrazolinones as trypanocidals: fragment-based design, synthesis, and pharmacological evaluation of nanomolar inhibitors of trypanosomal …

…, E van den Bogaart, E Chatelain, JR Ioset…

文献索引：Orrling, Kristina M.; Jansen, Chimed; Vu, Xuan Lan; Balmer, Vreni; Bregy, Patrick; Shanmugham, Anitha; England, Paul; Bailey, David; Cos, Paul; Maes, Louis; Adams, Emily; Van Den Bogaart, Erika; Chatelain, Eric; Ioset, Jean-Robert; Van De Stolpe, Andrea; Zorg, Stephanie; Veerman, Johan; Seebeck, Thomas; Sterk, Geert Jan; De Esch, Iwan J. P.; Leurs, Rob Journal of Medicinal Chemistry, 2012 , vol. 55, # 20 p. 8745 - 8756

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被引用次数: 24

摘要

Trypanosomal phosphodiesterases B1 and B2 (TbrPDEB1 and TbrPDEB2) play an important role in the life cycle of Trypanosoma brucei, the causative parasite of human African trypanosomiasis (HAT), also known as African sleeping sickness. We used homology modeling and docking studies to guide fragment growing into the parasite-specific P-pocket in the enzyme binding site. The resulting catechol pyrazolinones act as potent ...