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

Article abstract of DOI:10.1002/jlcr.2580360712

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, [¹³C]-, [¹⁴C]-, and [³H]-labeled LGD1069 is required. Herein, we describe synthetic methods for preparing isotopically labeled homologs of LGD 1069 as well as comparative competition binding data for [6,7-³H]-LGD1069 and [³H]-9-cis retinoic acid with RXR active retinoids. The final radiolabeled products, [6,7-³H]-LGD1069 and 3-[¹⁴C]-LGD1069 have specific activities of 56 Ci/mmol and 49 mCi/mmol, respectively. Radiochemical purities are 99.5% for [6,7-³H]-LGD1069 and 99.0% for 3-[¹⁴C]-LGD1069. The chemical purity is 99.0% for 3-[¹³CD₃]-LGD1069. Competition binding studies with known retinoids show similar K(d) values when either [6,7-³H]-LGD1069 or [³H]-9-cis retinoic acid is used as the radioligand.