|
|||||
|
|
Novel 3-O-carbamoyl erythromycin A derivatives (carbamolides) with activity against resistant staphylococcal and streptococcal isolates |
|
| Authors: | 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 |
| Institution: | 1. Pfizer Cardiovascular, Metabolic, and Endocrine Diseases (CVMED) Chemistry, 620 Memorial Dr, Cambridge, MA 02139, USA;2. Pfizer Structural Biology and Biophysics, Eastern Point Rd, Groton, CT 06340, USA;3. Cubist Pharmaceuticals, 65 Hayden Ave, Lexington, MA 02421, USA;4. Pfizer Primary Pharmacology Group, Eastern Point Rd, Groton, CT 06340, USA;5. Astra-Zeneca, 35 Gatehouse Lane, Waltham, MA 02451, USA;6. Pfizer Exploratory Discovery Chemistry, Eastern Point Rd, Groton, CT 06340, USA;7. Pfizer Computational Chemistry, Eastern Point Rd, Groton, CT 06340, USA |
| 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 (3.2 Å resolution). |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ | |