title: Synthesis and biological evaluation of non-peptidic cyclophilin ligands.
abstract: Peptidylprolyl isomerase cyclophilins play critical roles in a variety of biological processes. Recent findings that cyclophilins are present at high levels in the CNS and that cyclosporin A may possess neuroprotective/neurotrophic effects have prompted us to search for nonimmunosuppressant small molecule cyclophilin ligands. To this end, we report the lead identification through "virtual screening" and the synthesis of our first series of non-peptidic cyclophilin ligands, along with the preliminary biological results.
authors.affiliation: Department of Research, Guilford Pharmaceuticals, Inc., 6611 Tributary Street, Baltimore, Maryland 21224, USA. wuy@guilfordpharm.com
authors.forename: Yong-Qian
authors.initials: YQ
authors.lastname: Wu
authors.forename: Sergei
authors.initials: S
authors.lastname: Belyakov
authors.forename: Chi
authors.initials: C
authors.lastname: Choi
authors.forename: David
authors.initials: D
authors.lastname: Limburg
authors.forename: Bert E
authors.initials: BE
authors.lastname: Thomas IV
authors.forename: Mark
authors.initials: M
authors.lastname: Vaal
authors.forename: Ling
authors.initials: L
authors.lastname: Wei
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Wilkinson
authors.forename: Agnes
authors.initials: A
authors.lastname: Holmes
authors.forename: Mike
authors.initials: M
authors.lastname: Fuller
authors.forename: Jocelyn
authors.initials: J
authors.lastname: McCormick
authors.forename: Maureen
authors.initials: M
authors.lastname: Connolly
authors.forename: Tim
authors.initials: T
authors.lastname: Moeller
authors.forename: Joseph
authors.initials: J
authors.lastname: Steiner
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Hamilton
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D020650:Combinatorial Chemistry Techniques; D021984:Cyclophilin A / Q000037:antagonists & inhibitors*; D016208:Databases, Factual; D005727:Ganglia, Spinal / Q000187:drug effects / Q000648:ultrastructure; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects; D016501:Neurites / Q000187:drug effects; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D008024:Ligands; D018696:Neuroprotective Agents; D014508:Urea; D021984:Cyclophilin A