title: Discovery, SAR, synthesis, pharmacokinetic and biochemical characterization of A-192411: a novel fungicidal lipopeptide-(I).
abstract: The echinocandin class of cyclic lipopeptides has been simplified to discover potent antifungal compounds. Namely A-192411 shows good in vitro activity against common pathogenic yeasts and has an acceptable safety window in vivo. Discovery, limited SAR, synthesis, biochemical and pharmaco-dynamic profiles of A-192411 are presented.
authors.affiliation: Infectious Diseases Research, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064, USA. ybennani@athersys.com
authors.forename: Weibo
authors.initials: W
authors.lastname: Wang
authors.forename: Qun
authors.initials: Q
authors.lastname: Li
authors.forename: Lisa
authors.initials: L
authors.lastname: Hasvold
authors.forename: Beth
authors.initials: B
authors.lastname: Steiner
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Dickman
authors.forename: Hong
authors.initials: H
authors.lastname: Ding
authors.forename: Akyio
authors.initials: A
authors.lastname: Clairborne
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Chen
authors.forename: David
authors.initials: D
authors.lastname: Frost
authors.forename: Robert C
authors.initials: RC
authors.lastname: Goldman
authors.forename: Kennan
authors.initials: K
authors.lastname: Marsh
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Hui
authors.forename: Brian
authors.initials: B
authors.lastname: Cox
authors.forename: Angela
authors.initials: A
authors.lastname: Nilius
authors.forename: Darlene
authors.initials: D
authors.lastname: Balli
authors.forename: Paul
authors.initials: P
authors.lastname: Lartey
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Plattner
authors.forename: Youssef L
authors.initials: YL
authors.lastname: Bennani
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D002175:Candida / Q000187:drug effects / Q000378:metabolism; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004285:Dogs; D015195:Drug Design; D005658:Fungi / Q000187:drug effects / Q000378:metabolism*; D005936:Glucans / Q000378:metabolism; D000882:Haplorhini; D051379:Mice; D008826:Microbial Sensitivity Tests; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D012331:RNA, Fungal / Q000096:biosynthesis; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: C476327:A-192411; D000935:Antifungal Agents; D005936:Glucans; D009842:Oligopeptides; D012331:RNA, Fungal