Novel Cephalosporins Selectively Active on Nonreplicating Mycobacterium tuberculosis

作者：Gold Ben; Smith Robert; Quyen Nguyen; Roberts Julia; Ling Yan; Quezada Landys Lopez; Somersan Selin; Warrier Thulasi; Little David; Pingle Maneesh; Zhang David; Ballinger Elaine; Zimmerman Matthew; Dartois Veronique; Hanson Paul; Mitscher Lester A; Porubsky Patrick; Rogers Steven; Schoenen Frank J; Nathan Carl^*; Aube Jeffrey^*

来源：Journal of Medicinal Chemistry, 2016, 59(13): 6027-6044.

DOI：10.1021/acs.jmedchem.5b01833

We report two series of novel cephalosporins that are bactericidal to Mycobacterium tuberculosis alone of the pathogens tested, which only kill M. tuberculosis when its replication is halted by conditions resembling those believed to pertain in the host, and whose bactericidal activity is not dependent upon or enhanced by clavulanate, a beta-lactamase inhibitor. The two classes of cephalosporins bear an ester or alternatively an oxadiazole isostere at C-2 of the cephalosporin ring system, a position that is almost exclusively a carboxylic acid in clinically used agents in the class. Representatives of the series kill M. tuberculosis within macrophages without toxicity tothe macrophages or other mammalian cells.

• 出版日期2016-7-14