ABSTRACT
The first series of 2'-substituted 2-(3'-carboxybicyclo[1.1.1]pentyl)glycine derivatives, (2R)- and (2S)-(2',2'-dichloro-3'-carboxybicyclo[1.1.1]pentyl)glycine (10) and (11), and 2-(2'-chloro-3'-carboxybicyclo[1.1.1]pentyl)glycine (12) were synthesized and evaluated as mGluR ligands. Compounds 11 and 12 were shown to be competitive group I mGluR antagonists. These results are also discussed in light of docking studies with both the active (closed) and inactive (open) conformations of mGluR1.
Subject(s)
Bridged Bicyclo Compounds/chemical synthesis , Bridged Bicyclo Compounds/pharmacology , Glycine/analogs & derivatives , Receptors, Metabotropic Glutamate/drug effects , Bridged Bicyclo Compounds/metabolism , Glycine/chemical synthesis , Glycine/metabolism , Glycine/pharmacology , Ligands , Magnetic Resonance Spectroscopy , Models, Molecular , Receptors, Metabotropic Glutamate/metabolism , Structure-Activity RelationshipABSTRACT
A facile six-step synthesis of 2,2,3,4,4-d5-androsterone-beta-D-glucuronide (1) starting from epiandrosterone (2) in 63% yield is described and compared with several alternative synthetic pathways. Compound 1 can be used as an internal standard in screening procedures for anabolic steroids to monitor the hydrolysis step of the steroid glucuronides prior to gas chromatography-mass spectrometry (GC-MS) analysis. Thus, a time consuming solid-phase extraction step to remove possible hydrolysis inhibitors can be omitted.
