Synthesis and Antiprotozoal Activity of Dicationic <i>m</i>-Terphenyl and 1,3-Dipyridylbenzene Derivatives
作者:Donald A. Patrick、Mohamed A. Ismail、Reem K. Arafa、Tanja Wenzler、Xiaohua Zhu、Trupti Pandharkar、Susan Kilgore Jones、Karl A. Werbovetz、Reto Brun、David W. Boykin、Richard R. Tidwell
DOI:10.1021/jm400508e
日期:2013.7.11
Bis-pyridylimidamide derivative 31 was 25 times more potent than benznidazole against T. cruzi and slightly more potent than amphotericin B against L. amazonensis. Terphenyldiamidine 1 and dipyridylbenzene analogues 23 and 25 each cured 4/4 mice infected with T. b. rhodesiense STIB900 with four daily 5 mg/kg intraperitoneal doses, as well as with single doses of ≤10 mg/kg. Derivatives 5 and 28 (prodrugs
4,4“-Diamidino-米-三联苯(1制备并在体外测定对抗T)和36类似物rypanosoma布氏罗得西亚,克氏锥虫,疟原虫和利什曼原虫亚马孙。23种化合物对T. b具有很高的活性。罗得西亚或恶性疟原虫。最值得注意的是脒1,10,和11与IC 50 4nM的反对的布氏锥虫 罗得香和二甲基四氢嘧啶类似物4和9(IC 50)对恶性疟原虫的值≤3 nM 。双吡啶基酰亚胺酰胺衍生物31对T的效力是苯并咪唑的25倍。克鲁氏菌对亚马逊乳酸杆菌的杀伤力比两性霉素B强。三联苯二胺1和二吡啶基苯类似物23和25分别治愈了感染T.b的4/4小鼠。罗得西亚STIB900具有四个每日5mg / kg的腹膜内剂量,以及与单次剂量的≤10毫克/公斤。衍生物5和28(前药1和25)每只治愈3/4只小鼠,每天四次口服25 mg / kg口服剂量。