二价阳离子 2,6-二苯基吡嗪及其氮类似物的合成及抗原生动物活性。
Synthesis and antiprotozoal activity of dicationic 2,6-diphenylpyrazines and aza-analogues.
机构信息
Department of Chemistry, Georgia State University, Atlanta, GA 30303-3083, USA; Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
出版信息
Bioorg Med Chem. 2013 Nov 1;21(21):6732-41. doi: 10.1016/j.bmc.2013.08.006. Epub 2013 Aug 13.
Dicationic 2,6-diphenylpyrazines, aza-analogues and prodrugs were synthesized; evaluated for DNA affinity, activity against Trypanosoma brucei rhodesiense (T. b. r.) and Plasmodium falciparum (P. f.) in vitro, efficacy in T. b. r. STIB900 acute and T. b. brucei GVR35 CNS mouse models. Most diamidines gave poly(dA-dT)2 ΔTm values greater than pentamidine, IC50 values: T. b. r. (4.8-37nM) and P. f. (10-52nM). Most diamidines and prodrugs gave cures for STIB900 model (11, 19a and 24b 4/4 cures); 12 3/4 cures for GVR35 model. Metabolic stability half-life values for O-methylamidoxime prodrugs did not correlate with STIB900 results.
二嗪并[2,6-b]吡嗪类化合物、氮类似物和前药被合成；评估它们与 Trypanosoma brucei rhodesiense（T. b. r.）和 Plasmodium falciparum（P. f.）的体外 DNA 亲和力、活性、在 T. b. r. STIB900 急性和 T. b. brucei GVR35 CNS 小鼠模型中的疗效。大多数二脒类化合物的 poly(dA-dT)2 ΔTm 值大于戊二脒，IC50 值：T. b. r.（4.8-37nM）和 P. f.（10-52nM）。大多数二脒类化合物和前药对 STIB900 模型（11、19a 和 24b 4/4 治愈）、GVR35 模型（12 治愈）具有疗效。O-甲基酰胺肟前药的代谢稳定性半衰期值与 STIB900 结果没有相关性。
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