title: Synthesis and antibacterial activity of novel water-soluble nocathiacin analogs.
abstract: Semi-synthetic water-soluble analogs were synthesized from nocathiacin I through the formation of a versatile intermediate nocathiacin amine 5, and subsequent transformation via reductive amination, acylation or urea formation. Several of the novel analogs displayed much improved aqueous solubility over 1, while retained antibacterial activity. Compound 15 and 16 from the amide series, demonstrated excellent in vitro and in vivo antibacterial activity.
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: Emily
authors.initials: E
authors.lastname: Hickey
authors.forename: Kun
authors.initials: K
authors.lastname: Liu
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013293:Enterococcus faecalis / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012995:Solubility; D013211:Staphylococcus aureus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014867:Water / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D010456:Peptides, Cyclic; D013844:Thiazoles; C463319:nocathiacin I; D014867:Water