Ramnauth Jailall, Surman Mathew D, Sampson Peter B, Forrest Bryan, Wilson Jeff, Freeman Emily, Manning David D, Martin Fernando, Toro Andras, Domagala Megan, Awrey Donald E, Bardouniotis Elias, Kaplan Nachum, Berman Judd, Pauls Henry W
Affinium Pharmaceuticals Inc., 1243 Islington Avenue, Suite 600, Toronto, ON, Canada M8X 1Y9.
Bioorg Med Chem Lett. 2009 Sep 15;19(18):5359-62. doi: 10.1016/j.bmcl.2009.07.094. Epub 2009 Jul 23.
In the search for new antibacterial agents, the enzyme FabI has been identified as an attractive target. Employing a structure guided approach, the previously reported ene-amide series of FabI inhibitors were expanded to include 2,3,4,5-tetrahydro-1H-pyrido[2,3-b and e][1,4]diazepines. These novel series incorporate additional H-bonding functions and can be more water soluble than their naphthyridinone progenitors; diazepine 16c is shown to be efficacious in a mouse infection model.
在寻找新型抗菌剂的过程中，酶FabI已被确定为一个有吸引力的靶点。采用结构导向方法，先前报道的烯酰胺类FabI抑制剂系列得以扩展，纳入了2,3,4,5-四氢-1H-吡啶并[2,3-b和e][1,4]二氮杂卓。这些新型系列引入了额外的氢键功能，并且比其萘啶酮前体具有更高的水溶性；二氮杂卓16c在小鼠感染模型中显示出有效性。
