Synthesis and bioactivity of new Finasteride conjugate

• Published in: Bioorganic & medicinal chemistry letters Vol. 21; no. 11; pp. 3439 - 3442
• Main Authors: Shuang, Zhao, Jiazhen, Wu, Lijuan, Yang, Zhuo, Li, Dahai, Yu, Jinfeng, Li, Jing, Yu, Yongtao, Liang, En-si, Wang, Xuexun, Fang
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.06.2011; Elsevier
• Subjects: 5-alpha Reductase Inhibitors - chemical synthesis; 5-alpha Reductase Inhibitors - chemistry; 5-alpha Reductase Inhibitors - pharmacology; 5α-Reductase; Acylation; Animals; Biological and medical sciences; Cell Proliferation - drug effects; Conjugates; Disease Models, Animal; Finasteride; Finasteride - chemical synthesis; Finasteride - chemistry; Finasteride - pharmacology; Food and Drug Administration; hyperplasia; Inhibitory Concentration 50; Magnetic Resonance Spectroscopy; Male; Medical sciences; nuclear magnetic resonance spectroscopy; Pharmacology. Drug treatments; Polimod; Prostatic Hyperplasia - pathology; Rats; Synthesis; testosterone; toxicity; Urinary system; United States; Conjugates; Polimod; Synthesis; Finasteride; 5α-Reductase; Antineoplastic agent; Steroid; Prostate disease; Rat; Antihormone; Benign prostatic hyperplasia; Benign neoplasm; Chemical synthesis; Male genital diseases; 3-Oxo-5α-steroid 4-dehydrogenase; Acylation; Pidotimod; Urinary system disease; Enzyme; Rodentia; Antiandrogen; Azasteroid; Biological activity; Vertebrata; Mammalia; Animal; Oxidoreductases; Conjugated compound; Histochemistry
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.03.102

Finasteride is a synthetic 4-azasteroid compound that acts by inhibiting type II 5α-reductase, the enzyme that converts the androgen testosterone to 5α-dihydrotestosterone. It was approved by the US FDA for the treatment of benign prostatic hyperplasia and male pattern baldness. Here the acylation product of Finasteride C-18 amide N-polimod was synthesized by employing acylation reaction with polimod amide as a pivotal intermediate. The structure of the key intermediate and target molecule was confirmed by infrared spectrum, 1H NMR and 13C NMR spectra and mass spectrum, and the inhibition of the steroid 5α-reductase and the rats’ benign prostatic hyperplasia by the new Finasteride conjugate and Finasteride was also determined. The inhibition of the Finasteride conjugate on 5α-reductase was stronger than that of Finasteride. Prostate hyperplasia of rats was reduced by Finasteride conjugate treatment similar to the Finasteride treatment. However, the Finasteride conjugate treated animals showed better viable condition than the Finasteride treated ones, suggesting the new compound may have improved toxicity profile than Finasteride.