Premium
Syntheses of the tricyclic cores of clozapine, dibenzo[b,f][1,4]thiazepin‐11(10H)‐one, and dibenzo[b,f][1,4]oxazepin‐11(10H)‐one in C‐14 labeled form by [ 14 C]carbonylation
Author(s) -
Elmore Charles S.,
Dorff Peter N.,
Richard Heys J.
Publication year - 2010
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.1802
Subject(s) - clozapine , chemistry , tricyclic , covalent bond , population , stereochemistry , carbonylation , biochemistry , organic chemistry , psychology , psychiatry , schizophrenia (object oriented programming) , carbon monoxide , catalysis , demography , sociology
Clozapine has been demonstrated to bind covalently to proteins as a result of metabolic activation that has been proposed to be a precursor to the serious side effects including death that occur in a small percentage of the population. The covalent modification of proteins by clozapine has been studied by several groups and is well documented; therefore, the department of drug metabolism desired to use [ 14 C]clozapine as a positive control for covalent binding assays. The preparation of [ 14 C]clozapine was first conducted using a previous reported route and then using a new route that utilized [ 14 C]carbonylation as the isotope incorporating step. While this route worked, it was not deemed superior to the previous route. However, this methodology proved quite effective in preparing C‐14 labeled dibenzothiazepine and dibenzoxapine ring systems. Copyright © 2010 John Wiley & Sons, Ltd.