Ratna Sekhar Bolla1, Narasimha Murthy Gandikota1, Ivaturi Venkata Kasi Viswanath1.
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. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
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. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Entities:
Keywords:
4-dione; 5-dimethyl imidazolidine-2; Bucherer-Bergs hydantoin synthesis; [2H6]- 5; [2H6]-nilutamide; antineoplastic; deuterium labeling; non-steroidal antiandrogen; prostate cancer.
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Year: 2019
PMID： 30854946 DOI： 10.2174/1874471012666181130162731
Source DB: PubMed Journal: Curr Radiopharm ISSN： 1874-4710