Synthesis and Activity of Analogoues of SB-219383: Novel Potent Inhibitors of Bacterial Tyrosyl tRNA Synthetase

摘要

SB-219383 is a naturally occurring antibiotic, which acts by inhibition of tyrosyl tRNA synthetase. Semi-synthetic derivatives of SB-219383 were prepared with the objective of elucidating the key features required for inhibition of tyrosyl tRNA synthetae in order to improve the antibacterial activity. Some ester and amide derivatives as well as monocyclic analogues exhibited sub-nanomolar inhibitory activity against tyrosyl tRNA synthetase.