Preparation of novel anthranilic acids as antibacterial agents. Extensive evaluation of alternative amide bioisosteres connecting the A- and the B-rings.

Atli Thorarensen, Brian D Wakefield, Donna L Romero, Keith R Marotti, Michael T Sweeney, Gary E Zurenko, Douglas C Rohrer, Fusen Han, Garold L Bryant

文献索引：Bioorg. Med. Chem. Lett. 17 , 2823, (2007)

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摘要

In the past few years, a significant effort has been devoted by Pharmacia toward the discovery of novel antibiotics. We have recently described the identification of an anthranilic acid lead 1 and the optimization resulting in the advanced lead 2. In this report, we describe the preparation of several selected amide bioisosteres connecting the A- and the B-rings. The E-alkene provided a rigid analog with equal potency to the corresponding amide. This indicates that the amide is not a recognition element rather acts as an appropriate spatial linker of the two important aryl A and B rings. The work here clearly demonstrates that the amide linker can be replaced with several functionalities without significant deterioration in the MIC activity.