892181-10-1Relevant academic research and scientific papers
Optimization of chloronitrobenzamides (CNBs) as therapeutic leads for human African trypanosomiasis (HAT)
Hwang, Jong Yeon,Smithson, David,Zhu, Fangyi,Holbrook, Gloria,Connelly, Michele C.,Kaiser, Marcel,Brun, Reto,Guy, R. Kiplin
, p. 2850 - 2860 (2013/05/21)
We previously reported the discovery of the activity of chloronitrobenzamides (CNBs) against bloodstream forms of Trypanosoma brucei. Herein we disclose extensive structure-activity relationship and structure-property relationship studies aimed at identification of tractable early leads for clinical development. These studies revealed a promising lead compound, 17b, that exhibited nanomolar potency against T. brucei (EC 50 = 27 nM for T. b. brucei, 7 nM for T. b. rhodesiense, and 2 nM for T. b. gambiense) with excellent selectivity for parasite cells relative to mammalian cell lines (EC50 > 25 μM). In addition compound 17b displayed suitable physiochemical characteristics and microsomal stability (t1/2 > 4 h for human and mouse) to justify pursuing in vivo studies.
