title: Novel 3-O-carbamoyl erythromycin A derivatives (carbamolides) with activity against resistant staphylococcal and streptococcal isolates.
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).
authors: Pfizer Cardiovascular, Metabolic, and Endocrine Diseases (CVMED) Chemistry, 620 Memorial Dr, Cambridge, MA 02139, USA. thomas.v.magee@pfizer.com
authors: Thomas V
authors: TV
authors: Magee
authors: Seungil
authors: S
authors: Han
authors: Sandra P
authors: SP
authors: McCurdy
authors: Thuy-Trinh
authors: TT
authors: Nguyen
authors: Karl
authors: K
authors: Granskog
authors: Eric S
authors: ES
authors: Marr
authors: Bruce A
authors: BA
authors: Maguire
authors: Michael D
authors: MD
authors: Huband
authors: Jinshan Michael
authors: JM
authors: Chen
authors: Timothy A
authors: TA
authors: Subashi
authors: Veerabahu
authors: V
authors: Shanmugasundaram
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D034301:Deinococcus / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D004926:Escherichia coli / Q000378:metabolism; D008782:Methylurea Compounds / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D017434:Protein Structure, Tertiary; D011759:Pyrrolidines / Q000737:chemistry; D054681:Ribosome Subunits, Large, Bacterial / Q000737:chemistry / Q000378:metabolism; D013210:Staphylococcus / Q000187:drug effects / Q000302:isolation & purification*; D013291:Streptococcus / Q000187:drug effects / Q000302:isolation & purification*
chemical_list: D000900:Anti-Bacterial Agents; D008782:Methylurea Compounds; D011759:Pyrrolidines; D004917:Erythromycin; C032519:pyrrolidine; C006892:carbamol