title: Glyco-optimization of aminoglycosides: new aminoglycosides as novel anti-infective agents.
abstract: Glyco-optimization (OPopS) of aminoglycosides has been performed by replacing the existing sugar moiety with a variety of sugar derivatives. Glycosylation of the 6-position of nebramine provided a library of novel 4,6-linked aminoglycosides (AMGs). Among them, compounds 8b,g,i,l, and 8u with 2"-amino, 2",3"-diamino, 2",4"-diamino, 3",4"-diamino, 3"-amino groups, respectively, showed significant antimicrobial activity against Gram-(+) and -(-) bacteria. Several were particularly potent against Pseudomonus aeruginosa with MICs in the 1-2 microg/mL range.
authors.affiliation: Department of Chemistry, Optimer Pharmaceuticals, Inc., 10110 Sorrento Valley Road, Suite C, San Diego, CA 92121, USA. ssucheck@optimerpharma.com
authors.forename: Sulan
authors.initials: S
authors.lastname: Yao
authors.forename: Paulo W M
authors.initials: PW
authors.lastname: Sgarbi
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Marby
authors.forename: David
authors.initials: D
authors.lastname: Rabuka
authors.forename: Sean M
authors.initials: SM
authors.lastname: O'Hare
authors.forename: Mayling L
authors.initials: ML
authors.lastname: Cheng
authors.forename: Mrunali
authors.initials: M
authors.lastname: Bairi
authors.forename: Changyong
authors.initials: C
authors.lastname: Hu
authors.forename: San-Bao
authors.initials: SB
authors.lastname: Hwang
authors.forename: Chan-Kou
authors.initials: CK
authors.lastname: Hwang
authors.forename: Yoshi
authors.initials: Y
authors.lastname: Ichikawa
authors.forename: Pamela
authors.initials: P
authors.lastname: Sears
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Sucheck
mesh_terms: D000617:Aminoglycosides / Q000138:chemical synthesis* / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D014312:Trisaccharides / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000617:Aminoglycosides; D000890:Anti-Infective Agents; D014312:Trisaccharides