Design and synthesis of simplified sordaricin derivatives as inhibitors of fungal protein synthesis.
A reduction of the tetracyclic skeleton of sordarins and sordaricins to a cyclopentane ring bearing the pharmacophore functional groups led to new derivatives retaining part of their in vitro and whole-cell activity.
Cuevas
J C
JC
Glaxo Wellcome, S.A., Research Department, Parque Tecnológico de Madrid, Spain.
Lavandera
J L
JL
Martos
J L
JL
D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D001682:Biological Availability; D002176:Candida albicans / Q000187:drug effects / Q000378:metabolism; D002474:Cell-Free System; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005656:Fungal Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D051379:Mice; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D011500:Protein Synthesis Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship