European Journal of Medicinal Chemistry ( IF 6.0 ) Pub Date : 2020-05-19 , DOI: 10.1016/j.ejmech.2020.112409 Apeng Wang 1 , Chao Ma 1 , Yun Chai 2 , Xiujun Liu 1 , Kai Lv 1 , Lei Fu 3 , Bin Wang 3 , Xuedong Jia 4 , Mingliang Liu 1 , Yu Lu 3
|
A series of new benzothiazinone derivatives containing a symmetric 2-benzyl-2,7-diazaspiro[3.5]nonane moiety, based on the structure of LK02 discovered in our lab, were designed and synthesized. With one exception 3, all of them show excellent in vitro activity against both drug-sensitive and clinically isolated multidrug-resistant Mycobacterium tuberculosis (MTB) strains (MIC: < 0.016 μg/mL). Compound 2d with a methyl group at the benzylic carbon, was identified to have good safety and significant efficacy in an acute mouse model of TB, as well as better PK profiles than PBTZ169.
中文翻译：
鉴定含有2-苄基-2,7-二氮杂螺[3.5]壬烷部分的苯并噻嗪酮类药物作为新的抗结核药。
根据在我们实验室中发现的LK02的结构，设计并合成了一系列含有对称的2-苄基-2,7-二氮杂螺[3.5]壬烷部分的新的苯并噻嗪酮衍生物。除3个例外外，所有这些药物均对药物敏感和临床分离的耐多药结核分枝杆菌（MTB）菌株（MIC：<0.016μg/ mL）表现出优异的体外活性。经鉴定，在苄基碳原子上具有甲基的化合物2d在TB的急性小鼠模型中具有良好的安全性和显着的功效，并且比PBTZ169具有更好的PK特性。
京公网安备 11010802027423号