ABSTRACT
The first structure-activity relationships for a benzothiazole scaffold acting as an antagonist at GPR35 is presented. Analogues were designed based on a lead compound that was previously determined to have selective activity as a GPR35 antagonist. The synthetic route was modular in nature to independently explore the role of the middle and both ends of the scaffold. The activities of the analogues illustrate the importance of all three segments of the compound.
Subject(s)
Benzothiazoles/chemistry , Receptors, G-Protein-Coupled/antagonists & inhibitors , Benzothiazoles/chemical synthesis , Benzothiazoles/metabolism , Cell Line, Tumor , Humans , Inhibitory Concentration 50 , Protein Binding , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Structure-Activity RelationshipABSTRACT
The conversion of readily available silylalkynes, iodobenzene diacetate, and azide anions was utilized to form and react cyanocarbenes. A copper(II)-catalyzed reaction was found to react in a different manner. Both of these methods benefit from the formation and in situ reaction of hypervalent iodonium alkynyl triflates in O-H insertion reactions.
