[14C] and [3H]‐labelling of Ragaglitazar: A dual acting PPARα and PPARγ agonist with hypolipidemic and anti‐diabetic activity

Currently, Ragaglitazar is being developed as a drug for the treatment of hyperglycaemia and hyperlipidemia in patients with type 2 diabetes. Here, we report the labelling of Ragaglitazar with carbon-14 and tritium for in vivo and in vitro investigations. Two different carbon-14 labelled as well as two different tritium labelled tracers of Ragaglitazar were synthesised. The carbon-14 label was introduced from either ethyl bromo[2-14C]acetate (5 steps/33% overall yield) or [U-14C]phenoxazine (4 steps/48% overall yield). Tritium was incorporated either by catalytic tritiation of an alkene precursor followed by chiral HPLC separation (2 steps/17% overall yield) or by catalytic tritium–halogen exchange of an aryl bromide precursor (2 steps/68% overall yield). Copyright © 2003 John Wiley & Sons, Ltd.