title: Synthesis and antibacterial activity of pentacyclines: a novel class of tetracycline analogs.
abstract: Employing a highly efficient total synthesis approach, we synthesized and evaluated for antibacterial activity diverse and novel pentacycline analogs with systematic variations at C7, C8, C9, and C10. Certain substitution groups, as well as substitution patterns at various positions, were found to be preferred for increased antibacterial activity. A number of pentacycline analogs displayed potent activity in vitro and in vivo, especially against Gram-positive organisms. Several analogs have also shown promising oral bioavailability in rats and cynomolgus monkey.
authors.affiliation: Tetraphase Pharmaceuticals, Watertown, MA 02472, USA.
authors.forename: Cuixiang
authors.initials: C
authors.lastname: Sun
authors.forename: Diana K
authors.initials: DK
authors.lastname: Hunt
authors.forename: Roger B
authors.initials: RB
authors.lastname: Clark
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: Xiao-Yi
authors.initials: XY
authors.lastname: Xiao
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019540:Area Under Curve; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D008252:Macaca fascicularis; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D058990:Molecular Targeted Therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013754:Tetracyclines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D013754:Tetracyclines