Syntheses of dual‐radioisotope‐labeled CP‐I, a GABAA receptor partial agonist

Abstract

AbstractCP‐I is a potent subtype‐selective GABAA receptor partial agonist. Owing to its significant metabolic cleavage at C8 observed in preliminary biotransformation studies with non‐radiolabeled CP‐I, the syntheses of CP‐I labeled at the right or left hand side with 14C or labeled with 3H at the right hand side were required. The two compounds labeled with 14C at the left or right hand side were synthesized in 2 and 5 radio‐synthetic steps using [14C]2‐chloroacetyl chloride and [14C]NaCN as starting radiolabeled materials, respectively. CP‐I was labeled with tritium at the right hand side by a tritium de‐halogenation method. Batches of radiolabeled CP‐I were mixed to give dual‐radioisotope‐labeled CP‐I. An efficient approach to [14C]fluoropyridinyl imidazole was developed, and a short synthesis of iodo‐substituted fluoropyridinyl imidazole was also achieved. The details of these syntheses are discussed. Copyright © 2011 John Wiley & Sons, Ltd.