Bioorganic & Medicinal Chemistry Letters 2013-03-15

Novel 3-O-carbamoyl erythromycin A derivatives (carbamolides) with activity against resistant staphylococcal and streptococcal isolates.

Thomas V Magee, Seungil Han, Sandra P McCurdy, Thuy-Trinh Nguyen, Karl Granskog, Eric S Marr, Bruce A Maguire, Michael D Huband, Jinshan Michael Chen, Timothy A Subashi, Veerabahu Shanmugasundaram

Index: Bioorg. Med. Chem. Lett. 23(6) , 1727-31, (2013)

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Abstract

A novel series of 3-O-carbamoyl erythromycin A derived analogs, labeled carbamolides, with activity versus resistant bacterial isolates of staphylococci (including macrolide and oxazolidinone resistant strains) and streptococci are reported. An (R)-2-aryl substituent on a pyrrolidine carbamate appeared to be critical for achieving potency against resistant strains. Crystal structures showed a distinct aromatic interaction between the (R)-2-aryl (3-pyridyl for 4d) substituent on the pyrrolidine and G2484 (G2505, Escherichia coli) of the Deinococcus radiodurans 50S ribosome (3.2Å resolution).Copyright © 2013 Elsevier Ltd. All rights reserved.