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Synthesis of Deuterium Labeled 5, 5-Dimethyl-3-(α, α, α-trifluoro-4-nitro-m-tolyl) Hydantoin

[ Vol. 12 , Issue. 1 ]

Author(s):

Ratna Sekhar Bolla*, Narasimha Murthy Gandikota and Ivaturi Venkata Kasi Viswanath*   Pages 82 - 87 ( 6 )

Abstract:


Objective: Stable and non-radioactive isotope labeled compounds gained significance in recent drug discovery and other various applications such as bio-analytical studies. The modern bioanalytical techniques can study the adverse therapeutic effects of drugs by comparing isotopically labeled internal standards. A well-designed labeled compound can provide high-quality information about the identity and quantification of drug-related compounds in biological samples. This information can be very useful at key decision points in drug development. In this study, we tried to synthesize Nilutamide- d6 which can be useful to study the adverse effects of Nilutamide, and based on these can modify or widen the new drug derivatives. Nilutamide is a nonsteroidal antiandrogen which is used in the treatment of prostate cancer. The aim of this study was to develop a synthetic approach to prepare deuterium labeled [2H6]-5, 5-dimethylimidazolidine-2, 4-dione and [2H6]-nilutamide.

Methods: Since nilutamide is a derivative of hydantoin, it involves the synthesis of Dimethylhydantoin via Bucherer-Bergs hydantoin synthesis, followed by oxidative N-arylation with 4-iodo-1-nitro-2- (trifluoromethyl) benzene.

Conclusion: We successfully synthesized [2H6]-nilutamide and [2H6]-dimethylhydantoin with good isotopic purity, measured to be of adequate quality for use as internal standards in bio-analytical studies. A brief mechanistic study of Bucherer-Bergs hydantoin reaction was carried and the reason for possible H/D exchange was explained.

Keywords:

Bucherer-Bergs hydantoin synthesis, [2H6]- 5, 5-dimethyl imidazolidine-2, 4-dione, [2H6]-nilutamide, antineoplastic, non-steroidal antiandrogen, prostate cancer, deuterium labeling.

Affiliation:

Department of Chemistry, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Guntur Dist 522502, Department of Chemistry, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Guntur Dist 522502, Department of Chemistry, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Guntur Dist 522502

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