B. Markus et al., SYNTHESIS OF C-14-LABELED CGS 16949A (FADROZOLE HCL), A POTENT AROMATASE INHIBITOR, Journal of labelled compounds & radiopharmaceuticals, 39(11), 1997, pp. 885-890
Citations number
6
Categorie Soggetti
Chemistry Analytical","Pharmacology & Pharmacy","Biochemical Research Methods
CGS 16949A (Fadrozole HCl) is an aromatase inhibitor currently used in
Japan for the treatment of estrogen-dependent cancer. A C-14-labeled
form of this compound was synthesized for metabolism and pharmacokinet
ic studies. The synthesis pathway includes six steps, which are shown
in synthetic Scheme 2. Initially, 4-bromotoluene was reacted with [C-1
4]CuCN to yield 4-tolunitrile-[C-14]-cyano. The nitrile was brominated
on the a carbon to give an intermediate that was used to N-alkylate a
known imidazole analogue. The product was treated with thionyl chlori
de to convert a 3-hydroxy propyl moiety to its chloro analogue. Treatm
ent with potassium butoxide gave [C-14] fadrozole as the free base via
ring closure. Hydrogen chloride gas was used to give the desired salt
[C-14]CGS 16949A. Using this procedure, [C-14]CGS 16949A was prepared
with 97% radiochemical purity. The overall radiochemical yield for th
e synthesis was 1% from [C-14]KCN.