title: Nocathiacin analogs: Synthesis and antibacterial activity of novel water-soluble amides.
abstract: Novel water-soluble amide analogs were synthesized from nocathiacin I (1) through the formation of the carboxylic acid intermediate followed by coupling to primary or secondary amines. Several compounds with potent antibacterial activity and adequate water solubility were identified. Of these, compound 19 was selected for more extensive evaluation because of its excellent in vitro antibacterial activity and in vivo efficacy, as well as clean off-target screening.
authors.affiliation: Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. libo_xu@merck.com
authors.forename: Libo
authors.initials: L
authors.lastname: Xu
authors.forename: Amy K
authors.initials: AK
authors.lastname: Farthing
authors.forename: James F
authors.initials: JF
authors.lastname: Dropinski
authors.forename: Peter T
authors.initials: PT
authors.lastname: Meinke
authors.forename: Christine
authors.initials: C
authors.lastname: McCallum
authors.forename: Penny S
authors.initials: PS
authors.lastname: Leavitt
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Hickey
authors.forename: Lawrence
authors.initials: L
authors.lastname: Colwell
authors.forename: John
authors.initials: J
authors.lastname: Barrett
authors.forename: Kun
authors.initials: K
authors.lastname: Liu
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000737:chemistry*; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry
chemical_list: D000577:Amides; D000900:Anti-Bacterial Agents; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D010879:Piperazines; C463319:nocathiacin I; D014867:Water