Advent of Imidazo[1,2-a]pyridine-3-carboxamides with Potent Multi- and Extended Drug Resistant Antituberculosis Activity.
Advent of Imidazo[1,2-a]pyridine-3-carboxamides with Potent Multi- and Extended Drug Resistant Antituberculosis Activity.
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DOI：
10.1021/ml200036r
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发表时间：
2011-06-09
影响因子：
4.2
通讯作者：
Miller, Marvin J.
中科院分区：
文献类型：
--
作者：
Moraski, Garrett C.;Markley, Lowell D.;Hipskind, Philip A.;Boshoff, Helena;Cho, Sanghyun;Franzblau, Scott G.;Miller, Marvin J.
合成了9个2，7-二甲基咪唑并[1，2-a]吡啶-3-甲酰胺和1个2，6-二甲基咪唑并[1，2-a]嘧啶-3-甲酰胺。评价化合物对复制型、非复制型、多重和广泛耐药Mtb菌株的体外抗结核活性。其中7种药物对各种结核菌株的MIC 90值≤ 1 μM。针对7种非结核菌株以及其他非分枝杆菌生物体筛选了该类（1）的代表性化合物，并证明了显著的微生物选择性。进行用化合物1处理的Mtb的转录谱实验以给出作用模式的初步指示。最后，评估化合物1、3、4和6的体内ADME性质。2，7-二甲基咪唑并[1，2-a]吡啶-3-甲酰胺类化合物是一种类药物且可合成的抗结核药物，其对多重和广泛耐药结核病具有优异的选择性效力，并具有良好的药代动力学。
A set of nine 2,7-dimethylimidazo[1,2-a]pyridine-3-carboxamides and one 2,6-dimethylimidazo[1,2-a]pyrimidine-3-carboxamide were synthesized. The compounds were evaluated for their in vitro anti-tuberculosis activity versus replicating, non-replicating, multi- and extensive drug resistant Mtb strains. The MIC90 values of seven of these agents were ≤ 1 μM against the various tuberculosis strains tested. A representative compound of this class (1) was screened against seven non-tubercular strains as well as other non-mycobacteria organisms and demonstrated remarkable microbe selectivity. A transcriptional profiling experiment of Mtb treated with compound 1 was performed to give a preliminary indication of the mode of action. Lastly, the in vivo ADME properties of compounds 1, 3, 4, and 6 were assessed. The 2,7-dimethylimidazo[1,2-a]pyridine-3-carboxamides are a drug-like and synthetically accessible class of anti-TB agents that have excellent selective potency against multi- and extensive drug resistant TB and encouraging pharmacokinetics.
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影响因子：
3.6
作者：
LOMBARDINO, JG
通讯作者：
LOMBARDINO, JG
影响因子：
3.6
作者：
Katritzky, AR;Xu, YJ;Tu, HB
通讯作者：
Tu, HB
DOI：
10.1073/pnas.97.3.1252
发表时间：
2000-02-01
影响因子：
11.1
作者：
De Voss, JJ;Rutter, K;Barry, CE
通讯作者：
Barry, CE
影响因子：
64.8
作者：
Stover, CK;Warrener, P;Baker, WR
通讯作者：
Baker, WR
影响因子：
4.8
作者：
Boshoff, HIM;Myers, TG;Barry, CE
通讯作者：
Barry, CE