Identification of a 4-fluorobenzyl l-valinate amide benzoxaborole (AN11736) as a potential development candidate for the treatment of Animal African Trypanosomiasis (AAT).
Identification of a 4-fluorobenzyl l-valinate amide benzoxaborole (AN11736) as a potential development candidate for the treatment of Animal African Trypanosomiasis (AAT).
复制标题
DOI：
10.1016/j.bmcl.2017.11.028
复制
发表时间：
2018-01-01
影响因子：
2.7
通讯作者：
Liang H
中科院分区：
文献类型：
--
作者：
Akama T;Zhang YK;Freund YR;Berry P;Lee J;Easom EE;Jacobs RT;Plattner JJ;Witty MJ;Peter R;Rowan TG;Gillingwater K;Brun R;Nare B;Mercer L;Xu M;Wang J;Liang H
设计并合成了新型的L-缬氨酸酰胺苯并氧杂硼杂环戊烯及其类似物，并进行了构效关系研究，以优化其对刚果锥虫（Trypanosoma congolense）的生长抑制活性。congolense）和间日锥虫Trypanosoma vivax（T.间日疟原虫）寄生虫。该研究鉴别了4-氟苄基（1-羟基-7-甲基-1，3-二氢苯并[c][1，2]氧杂硼杂环戊烯-6-羰基）-1-缬氨酸酯（5，AN 11736），其显示对T. congolense和1.3nM对T.间日疟原虫，并证明10 mg/kg单剂量对两种T. congolense和T.小鼠感染模型（IP给药）和靶动物牛中的间日疟，肌肉注射给药。AN 11736已进入早期开发研究。
Novel l-valinate amide benzoxaboroles and analogues were designed and synthesized for a structure-activity-relationship (SAR) investigation to optimize the growth inhibitory activity against Trypanosoma congolense (T. congolense) and Trypanosoma vivax (T. vivax) parasites. The study identified 4-fluorobenzyl (1-hydroxy-7-methyl-1,3-dihydrobenzo[c][1,2]oxaborole-6-carbonyl)-l-valinate (5, AN11736), which showed IC50 values of 0.15 nM against T. congolense and 1.3 nM against T. vivax, and demonstrated 100% efficacy with a single dose of 10 mg/kg against both T. congolense and T. vivax in mouse models of infection (IP dosing) and in the target animal, cattle, dosed intramuscularly. AN11736 has been advanced to early development studies.
登录
查看更多内容
影响因子：
2.7
作者：
Li, Xianfeng;Zhang, Suoming;Wright, Jon
通讯作者：
Wright, Jon
影响因子：
2.6
作者：
Shaw, A. P. M.;Cecchi, G.;Robinson, T. P.
通讯作者：
Robinson, T. P.
影响因子：
2.7
作者：
Ding, Charles Z.;Zhang, Yong-Kang;Wright, Jon
通讯作者：
Wright, Jon
影响因子：
2.4
作者：
Giordani F;Morrison LJ;Rowan TG;DE Koning HP;Barrett MP
通讯作者：
Barrett MP