title: 8-Azatetracyclines: synthesis and evaluation of a novel class of tetracycline antibacterial agents.
abstract: A novel series of fully synthetic 8-azatetracyclines was prepared and evaluated for antibacterial activity. Compounds were identified that overcome both efflux (tet(K)) and ribosomal protection (tet(M)) tetracycline resistance mechanisms and are active against Gram-positive and Gram-negative organisms. Two compounds were identified that exhibit comparable efficacy to marketed tetracyclines in in vivo models of bacterial infection.
authors.affiliation: Tetraphase Pharmaceuticals, Inc, 480 Arsenal Street, Watertown, Massachusetts 02472, United States. rclark@tphase.com
authors.forename: Roger B
authors.initials: RB
authors.lastname: Clark
authors.forename: Minsheng
authors.initials: M
authors.lastname: He
authors.forename: Corey
authors.initials: C
authors.lastname: Fyfe
authors.forename: Denene
authors.initials: D
authors.lastname: Lofland
authors.forename: William J
authors.initials: WJ
authors.lastname: O'Brien
authors.forename: Louis
authors.initials: L
authors.lastname: Plamondon
authors.forename: Joyce A
authors.initials: JA
authors.lastname: Sutcliffe
authors.forename: Xiao-Yi
authors.initials: XY
authors.lastname: Xiao
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001682:Biological Availability; D004927:Escherichia coli Infections / Q000517:prevention & control; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D007275:Injections, Intravenous; D051379:Mice; D008826:Microbial Sensitivity Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000517:prevention & control; D013290:Streptococcal Infections / Q000517:prevention & control; D013329:Structure-Activity Relationship; D013753:Tetracycline Resistance / Q000187:drug effects; D013754:Tetracyclines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C558531:6-demethyl-6-deoxy-7-(dimethylamino)-8-azatetracycline; C558530:7-chloro-6-demethyl-6-deoxy-9-((3-(dimethylamino)-2,2-dimethylpropyl)amino)-8-azatetracycline; D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D013754:Tetracyclines