ABSTRACT
A functional cell-based screen identified 3-(4-chlorophenyl)-3-(2-(dimethylamino)ethyl)isochroman-1-one hydrochloride (AC-7954, 1) as a nonpeptidic agonist of the urotensin-II receptor. Racemic 1 had an EC50 of 300 nM at the human UII receptor and was highly selective. Testing of the enantiopure (+)- and (-)- 1 revealed that the UII receptor activity of racemic 1 resides primarily in (+)-1. Being a selective nonpeptidic druglike UII receptor agonist, (+)-1 will be useful as a pharmacological research tool and a potential drug lead.
Subject(s)
Chromans/chemistry , Receptors, Cell Surface/agonists , Receptors, G-Protein-Coupled , Animals , Chromans/pharmacology , Combinatorial Chemistry Techniques , Humans , Mice , Rats , Stereoisomerism , Structure-Activity RelationshipABSTRACT
Enantioenriched thiosulfinates have been obtained by dioxygenase- and chloroperoxidase-catalysed oxidation of 1,2-disulfides and dimethyl sulfoxide reductase-catalysed deoxygenation.
Subject(s)
Enzymes/chemistry , Oxygen/chemistry , Thiosulfonic Acids/chemistry , Acinetobacter/enzymology , Catalysis , Chloride Peroxidase/chemistry , Citrobacter/enzymology , Dioxygenases , Indicators and Reagents , Multienzyme Complexes/chemistry , Oxidation-Reduction , Oxygenases/chemistry , Pseudomonas putida/enzymology , StereoisomerismABSTRACT
A brief account is given of the role of preparative chromatography for the direct separation of enantiomers in the drug discovery process. Although it is not yet possible to predict the outcome of a chromatographic resolution attempt, and the optimisation procedure sometimes might be time-consuming, the technique is still indispensable as a means to obtain both enantiomers in pure form from a drug racemate for biological testing. The most suitable types of chiral stationary phases (CSPs) available for this purpose are discussed with special reference to loadability and compatibility with different mobile phase systems.