Synthesis and biological evaluation of novel unsaturated carboxysteroids as?human 5¦Á-reductase inhibitors: A legitimate approach

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• 作者：Saurabh Aggarwal^a ; ^{aggarwalsau@gmail.com} ; Suresh Thareja^a ; T.R. Bhardwaj^a ; ^b ; Jö ; rg Haupenthal^c ; R.W. Hartmann^d ; Manoj Kumar^a ; ^{mkgw4pu@yahoo.com} ; ^{manoj_uips@pu.ac.in}
• 关键词：17a-Aza steroids ; Benign prostatic hyperplasia ; Carboxysteroids ; Testosterone ; Epristeride ; Finasteride ; 5¦Á-Reductase
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：August, 2012
• 年：2012
• 卷：54
• 期：Complete
• 页码：728-739
• 全文大小：410 K

文摘

In the present study, novel steroidal 17a-substituted 3-cyano-17a-aza-D-homo-3,5-androstadien-17-ones (12-19) and 17a-substituted 17-oxo-17a-aza-D-homo-3,5-androstadien-3-oic acids (20-26) were synthesized from dehydroepiandrosterone acetate (6) along with 17-oxo-19-nor-3,5-androstadien-3-oic acid (30) through a multistep synthesis. Compounds were evaluated for their in?vitro 5¦Á-reductase inhibitory activity by measuring the conversion of [³H] androstenedione in human embryonic kidney (HEK) cells. In?vivo 5¦Á-reductase inhibitory activity was also determined using rat prostate weighing method. Compounds 21-23 and 25 showed potent inhibition of 5¦Á-reductase II enzyme with IC₅₀ values of 54.1?¡À?9.5, 22.1?¡À?2.4, 72.8?¡À?2.3 and 26.5?¡À?4.4?nM respectively as compared to Finasteride (30.3?nM) along with a significant (p?<?0.05) reduction in rat prostate weight.