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[ 14 C] and [ 3 H]‐labelling of Ragaglitazar: A dual acting PPARα and PPARγ agonist with hypolipidemic and anti‐diabetic activity
Author(s) -
Kristensen Jesper B.,
Johansen Steen K.,
Valsborg Jacob S.,
Martiny Lars,
Foged Christian
Publication year - 2003
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.690
Subject(s) - chemistry , tritium , yield (engineering) , labelling , catalysis , agonist , carbon 14 , chemical synthesis , specific activity , radiochemistry , medicinal chemistry , nuclear chemistry , organic chemistry , in vitro , receptor , biochemistry , enzyme , metallurgy , quantum mechanics , materials science , physics , nuclear physics
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‐ 14 C]acetate (5 steps/33% overall yield) or [U‐ 14 C]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.