title: Synthesis and bioactivity of new Finasteride conjugate.
abstract: 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, (1)H NMR and (13)C 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.
authors.affiliation: College of Life Science, Jilin University, Changchun 130021, PR China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Shuang
authors.forename: Wu
authors.initials: W
authors.lastname: Jiazhen
authors.forename: Yang
authors.initials: Y
authors.lastname: Lijuan
authors.forename: Li
authors.initials: L
authors.lastname: Zhuo
authors.forename: Yu
authors.initials: Y
authors.lastname: Dahai
authors.forename: Li
authors.initials: L
authors.lastname: Jinfeng
authors.forename: Yu
authors.initials: Y
authors.lastname: Jing
authors.forename: Liang
authors.initials: L
authors.lastname: Yongtao
authors.forename: Wang
authors.initials: W
authors.lastname: En-Si
authors.forename: Fang
authors.initials: F
authors.lastname: Xuexun
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000215:Acylation; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D018120:Finasteride / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011470:Prostatic Hyperplasia / Q000473:pathology; D051381:Rats
chemical_list: D058891:5-alpha Reductase Inhibitors; D018120:Finasteride