Synthesis and biological evaluation of non-peptidic cyclophilin ligands.
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.
Wu
Yong-Qian
YQ
Department of Research, Guilford Pharmaceuticals, Inc., 6611 Tributary Street, Baltimore, Maryland 21224, USA. wuy@guilfordpharm.com
Belyakov
Sergei
S
Choi
Chi
C
Limburg
David
D
Thomas IV
Bert E
BE
Vaal
Mark
M
Wei
Ling
L
Wilkinson
Douglas E
DE
Holmes
Agnes
A
Fuller
Mike
M
McCormick
Jocelyn
J
Connolly
Maureen
M
Moeller
Tim
T
Steiner
Joseph
J
Hamilton
Gregory S
GS
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
D008024:Ligands; D018696:Neuroprotective Agents; D014508:Urea; D021984:Cyclophilin A