Advancement of Imidazo[1,2-a]pyridines with Improved Pharmacokinetics and Nanomolar Activity Against Mycobacterium tuberculosis.
Advancement of Imidazo[1,2-a]pyridines with Improved Pharmacokinetics and Nanomolar Activity Against Mycobacterium tuberculosis.
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DOI：
10.1021/ml400088y
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发表时间：
2013-07-11
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.;Cramer, Jeffrey;Hipskind, Philip A.;Boshoff, Helena;Bailey, Mai A.;Aing, Torey;Ollinger, Juliane;Parish, Tanya;Miller, Marvin J.
合成了一组14个咪唑[1,2- A]吡啶-3-羧酰胺，并对其进行了抗结核分枝杆菌H37Rv的筛选。其中12种药物对复制菌的最小抑制浓度≤1 μM， 5种化合物（9、12、16、17和18）的MIC值≤0.006 μM。化合物13和18对MDR和XDR耐药临床Mtb菌株进行了筛选，其效力超过临床候选药物PA-824近10倍。采用口服和静脉给药的方法对化合物13和18在雄性小鼠体内的药动学进行了研究。这些结果表明，易于合成的咪唑[1,2-a]吡啶-3-羧酰胺是一类令人兴奋的新型强效、选择性抗结核药物，值得进一步开发。
A set of fourteen imidazo[1,2-a]pyridine-3-carboxamides was synthesized and screened against Mycobacterium tuberculosis H37Rv. The minimum inhibitory concentrations of twelve of these agents were ≤ 1 μM against replicating bacteria and five compounds (9, 12, 16, 17 and 18) had MIC values ≤ 0.006 μM. Compounds 13 and 18 were screened against a panel of MDR and XDR drug resistant clinical Mtb strains with the potency of 18 surpassing that of clinical candidate PA-824 by nearly 10 fold. The in vivo pharmacokinetics of compounds 13 and 18 were evaluated in male mice by oral (PO) and intravenous (IV) routes. These results indicate that readily synthesized imidazo[1,2-a]pyridine-3-carboxamides are an exciting new class of potent, selective anti-TB agents that merit additional development opportunities.
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DOI：
10.1073/pnas.0508392103
发表时间：
2006-01-10
影响因子：
11.1
作者：
Manjunatha, UH;Boshoff, H;Barry, CE
通讯作者：
Barry, CE
影响因子：
3.4
作者：
Ballell, Lluis;Bates, Robert H.;Young, Rob J.;Alvarez-Gomez, Daniel;Alvarez-Ruiz, Emilio;Barroso, Vanessa;Blanco, Delia;Crespo, Benigno;Escribano, Jaime;Gonzalez, Ruben;Lozano, Sonia;Huss, Sophie;Santos-Villarejo, Angel;Julio Martin-Plaza, Jose;Mendoza, Alfonso;Jose Rebollo-Lopez, Maria;Remuinan-Blanco, Modesto;Luis Lavandera, Jose;Perez-Herran, Esther;Javier Gamo-Benito, Francisco;Francisco Garcia-Bustos, Jose;Barros, David;Castro, Julia P.;Cammack, Nicholas
通讯作者：
Cammack, Nicholas
影响因子：
3.8
作者：
Zamek-Gliszczynski, Maciej J.;Sprague, Karen E.;Molina-Martin, Manuel
通讯作者：
Molina-Martin, Manuel
影响因子：
64.8
作者：
Stover, CK;Warrener, P;Baker, WR
通讯作者：
Baker, WR
影响因子：
4.2
作者：
Moraski, Garrett C.;Markley, Lowell D.;Hipskind, Philip A.;Boshoff, Helena;Cho, Sanghyun;Franzblau, Scott G.;Miller, Marvin J.
通讯作者：
Miller, Marvin J.