Nocathiacin analogs: Synthesis and antibacterial activity of novel water-soluble amides.
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.
Xu
Libo
L
Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. libo_xu@merck.com
Farthing
Amy K
AK
Dropinski
James F
JF
Meinke
Peter T
PT
McCallum
Christine
C
Leavitt
Penny S
PS
Hickey
Emily J
EJ
Colwell
Lawrence
L
Barrett
John
J
Liu
Kun
K
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
D000577:Amides; D000900:Anti-Bacterial Agents; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D010879:Piperazines; C463319:nocathiacin I; D014867:Water