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Syntheses of dual‐radioisotope‐labeled CP‐I, a GABA A receptor partial agonist
Author(s) -
Zhang Yinsheng,
Greenfield Laura,
Hong Yang
Publication year - 2011
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.1889
Subject(s) - chemistry , tritium , imidazole , agonist , halogenation , stereochemistry , partial agonist , chemical synthesis , receptor , chloroacetyl chloride , chloride , radiochemistry , organic chemistry , biochemistry , physics , nuclear physics , in vitro
CP‐I is a potent subtype‐selective GABA A receptor partial agonist. Owing to its significant metabolic cleavage at C 8 observed in preliminary biotransformation studies with non‐radiolabeled CP‐I, the syntheses of CP‐I labeled at the right or left hand side with 14 C or labeled with 3H at the right hand side were required. The two compounds labeled with 14 C at the left or right hand side were synthesized in 2 and 5 radio‐synthetic steps using [ 14 C]2‐chloroacetyl chloride and [ 14 C]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 [ 14 C]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.