title: Identification of a broad-spectrum azasordarin with improved pharmacokinetic properties.
abstract: The synthesis and antifungal activity of 5'- and 5'-6'-substituted azasordarin derivatives are described. Modification of the 5'-position led to the discovery of the spirocyclopentyl analogue 7g, which is the first azasordarin to register single-digit MIC values versus Aspergillus spp. Further investigation identified the 5'-i-Pr derivative 7b, which displays superior pharmacokinetic properties compared to other azasordarins.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. michael.serrano-wu@bms.com
authors.forename: Michael H
authors.initials: MH
authors.lastname: Serrano-Wu
authors.forename: Denis R St
authors.initials: DR
authors.lastname: Laurent
authors.forename: Tina M
authors.initials: TM
authors.lastname: Carroll
authors.forename: Marco
authors.initials: M
authors.lastname: Dodier
authors.forename: Qi
authors.initials: Q
authors.lastname: Gao
authors.forename: Patrice
authors.initials: P
authors.lastname: Gill
authors.forename: Claude
authors.initials: C
authors.lastname: Quesnelle
authors.forename: Anne
authors.initials: A
authors.lastname: Marinier
authors.forename: Charles E
authors.initials: CE
authors.lastname: Mazzucco
authors.forename: Alicia
authors.initials: A
authors.lastname: Regueiro-Ren
authors.forename: Terry M
authors.initials: TM
authors.lastname: Stickle
authors.forename: Dedong
authors.initials: D
authors.lastname: Wu
authors.forename: Hyekyung
authors.initials: H
authors.lastname: Yang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yang
authors.forename: Ming
authors.initials: M
authors.lastname: Zheng
authors.forename: Mary E
authors.initials: ME
authors.lastname: Zoeckler
authors.forename: Dolatrai M
authors.initials: DM
authors.lastname: Vyas
authors.forename: Balu N
authors.initials: BN
authors.lastname: Balasubramanian
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D001230:Aspergillus / Q000187:drug effects; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D006027:Glycosides / Q000737:chemistry; D007192:Indenes; D007275:Injections, Intravenous; D051379:Mice; D008826:Microbial Sensitivity Tests; D013141:Spiro Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D001372:Aza Compounds; D006027:Glycosides; D007192:Indenes; D013141:Spiro Compounds; C003329:sordarin