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Syntheses of isotopically labeled 4‐[1‐(3,5,5,8,8‐pentamethyl‐5,6,7,8‐tetrahydro‐2‐naphthyl)ethenyl]benzoic acid (LGD1069), a potent retinoid x receptor‐selective ligand
Author(s) -
Zhang Lin,
Badea Beth Ann,
Enyeart Debra,
Berger Elaine M.,
Mais Dale E.,
Boehm Marcus F.
Publication year - 1995
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.2580360712
Subject(s) - chemistry , retinoid , benzoic acid , radioligand , ligand (biochemistry) , stereochemistry , retinoid x receptor , chemical synthesis , bioavailability , retinoid x receptor beta , retinoid x receptor alpha , retinoic acid receptor , retinoic acid , receptor , nuclear receptor , in vitro , biochemistry , pharmacology , transcription factor , medicine , gene
LGD1069, 4‐[1‐(3,5,5,8,8‐pentamethyl‐5,6,7,8‐tetrahydro‐2‐naphthyl)ethenyl] benzoic acid, is the first retinoid X receptor (RXR) selective retinoid to enter clinical trials for treatment of dermatological diseases and cancer. In order to examine biological properties such as receptor binding, metabolism and bioavailability, [ 13 C]‐, [ 14 C]‐, and [ 3 H]‐labeled LGD1069 is required. Herein, we describe synthetic methods for preparing isotopically labeled homologs of LGD1069 as well as comparative competition binding data for [6,7‐ 3 H]‐LGD1069 and [ 3 H]‐9‐ cis retinoic acid with RXR active retinoids. The final radiolabeled products, [6,7‐ 3 H]‐LGD1069 and 3‐[ 14 C]‐LGD1069 have specific activities of 56 Ci/mmol and 49 mCi/mmol, respectively. Radiochemical purities are 99.5% for [6,7‐ 3 H]‐LGD1069 and 99.0% for 3‐[ 14 C]‐LGD1069. The chemical purity is 99.0% for 3‐[ 13 CD 3 ]‐LGD1069. Competition binding studies with known retinoids show similar K d values when either [6,7‐ 3 H]‐LGD1069 or [ 3 H]‐9‐ cis retinoic acid is used as the radioligand.