发现吲唑衍生物作为一类新型细菌DNA回旋酶B抑制剂
Discovery of Indazole Derivatives as a Novel Class of Bacterial Gyrase B Inhibitors.
作者信息
Zhang Jing, Yang Qingyi, Romero Jan Antoinette C, Cross Jason, Wang Bin, Poutsiaka Katherine M, Epie Felix, Bevan Douglas, Wu Yuchuan, Moy Terence, Daniel Anu, Chamberlain Brian, Carter Nicole, Shotwell Joseph, Arya Anu, Kumar Vipul, Silverman Jared, Nguyen Kien, Metcalf Chester A, Ryan Dominic, Lippa Blaise, Dolle Roland E
机构信息
Cubist Pharmaceuticals Inc. , Lexington, Massachusetts 02421, United States.
出版信息
ACS Med Chem Lett. 2015 Sep 8;6(10):1080-5. doi: 10.1021/acsmedchemlett.5b00266. eCollection 2015 Oct 8.
Antibacterials with a novel mechanism of action offer a great opportunity to combat widespread antimicrobial resistance. Bacterial DNA Gyrase is a clinically validated target. Through physiochemical property optimization of a pyrazolopyridone hit, a novel class of GyrB inhibitors were discovered. Guided by structure-based drug design, indazole derivatives with excellent enzymatic and antibacterial activity as well as great animal efficacy were discovered.
具有新型作用机制的抗菌药物为对抗广泛存在的抗菌耐药性提供了绝佳机会。细菌DNA旋转酶是一个经过临床验证的靶点。通过对吡唑并吡啶先导化合物进行理化性质优化，发现了一类新型的GyrB抑制剂。在基于结构的药物设计指导下，发现了具有优异酶活性和抗菌活性以及良好动物药效的吲唑衍生物。
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