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

Author(s): Ratna Sekhar Bolla*, Narasimha Murthy Gandikota, Ivaturi Venkata Kasi Viswanath*

Journal Name: Current Radiopharmaceuticals

Volume 12 , Issue 1 , 2019

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Graphical 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.

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Article Details

Year: 2019
Published on: 04 March, 2019
Page: [82 - 87]
Pages: 6
DOI: 10.2174/1874471012666181130162731
Price: $65

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