Discovery, SAR, synthesis, pharmacokinetic and biochemical characterization of A-192411: a novel fungicidal lipopeptide-(I).
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.
Wang
Weibo
W
Infectious Diseases Research, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064, USA. ybennani@athersys.com
Li
Qun
Q
Hasvold
Lisa
L
Steiner
Beth
B
Dickman
Daniel A
DA
Ding
Hong
H
Clairborne
Akyio
A
Chen
Hui-Ju
HJ
Frost
David
D
Goldman
Robert C
RC
Marsh
Kennan
K
Hui
Yu-Hua
YH
Cox
Brian
B
Nilius
Angela
A
Balli
Darlene
D
Lartey
Paul
P
Plattner
Jacob J
JJ
Bennani
Youssef L
YL
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
C476327:A-192411; D000935:Antifungal Agents; D005936:Glucans; D009842:Oligopeptides; D012331:RNA, Fungal