title: Heterocyclyl Tetracyclines. 1. 7-Trifluoromethyl-8-Pyrrolidinyltetracyclines: Potent, Broad Spectrum Antibacterial Agents with Enhanced Activity against Pseudomonas aeruginosa.
abstract: Utilizing a total synthesis approach, the first 8-heterocyclyltetracyclines were designed, synthesized, and evaluated against panels of tetracycline- and multidrug-resistant Gram-positive and Gram-negative pathogens. Several compounds with balanced, highly potent in vitro activity against a broad range of bacterial isolates were identified through structure-activity relationships (SAR) studies. One compound demonstrated the best antibacterial activity against Pseudomonas aeruginosa both in vitro and in vivo for tetracyclines reported to date.
authors.affiliation: Discovery Chemistry, ‡Microbiology, Tetraphase Pharmaceuticals , 480 Arsenal Way, Watertown, Massachusetts 02472, United States.
authors.forename: Yonghong
authors.identifier: 0000-0001-9709-4530
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Discovery Chemistry, ‡Microbiology, Tetraphase Pharmaceuticals , 480 Arsenal Way, Watertown, Massachusetts 02472, United States.
authors.forename: Cuixiang
authors.initials: C
authors.lastname: Sun
authors.affiliation: Discovery Chemistry, ‡Microbiology, Tetraphase Pharmaceuticals , 480 Arsenal Way, Watertown, Massachusetts 02472, United States.
authors.forename: Diana K
authors.initials: DK
authors.lastname: Hunt
authors.affiliation: Discovery Chemistry, ‡Microbiology, Tetraphase Pharmaceuticals , 480 Arsenal Way, Watertown, Massachusetts 02472, United States.
authors.forename: Corey
authors.initials: C
authors.lastname: Fyfe
authors.affiliation: Discovery Chemistry, ‡Microbiology, Tetraphase Pharmaceuticals , 480 Arsenal Way, Watertown, Massachusetts 02472, United States.
authors.forename: Chi-Li
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Discovery Chemistry, ‡Microbiology, Tetraphase Pharmaceuticals , 480 Arsenal Way, Watertown, Massachusetts 02472, United States.
authors.forename: Trudy H
authors.initials: TH
authors.lastname: Grossman
authors.affiliation: Discovery Chemistry, ‡Microbiology, Tetraphase Pharmaceuticals , 480 Arsenal Way, Watertown, Massachusetts 02472, United States.
authors.forename: Joyce A
authors.initials: JA
authors.lastname: Sutcliffe
authors.affiliation: Discovery Chemistry, ‡Microbiology, Tetraphase Pharmaceuticals , 480 Arsenal Way, Watertown, Massachusetts 02472, United States.
authors.forename: Xiao-Yi
authors.initials: XY
authors.lastname: Xiao
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D054879:Halogenation; D006801:Humans; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D011760:Pyrrolidinones / Q000737:chemistry / Q000494:pharmacology; D013753:Tetracycline Resistance; D013754:Tetracyclines / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D011760:Pyrrolidinones; D013754:Tetracyclines