Design synthesis and evaluation of novel steroidal 5and#945; reductase inhibitors

Abstract

Benign prostatic hyperplasia (BPH), the leading disorder in aging males, is characterized by a progressive enlargement of prostatic tissue, resulting in obstruction of the proximal urethra and causes urinary flow disturbances. Suppression of DHT biosynthesis by 5and#945;-reductase inhibitors (5and#945;-RI) is a logical treatment for BPH, as abnormally high activity of the enzyme with excessive DHT levels has been observed in peripheral tissues of humans with LUTS. The work reported herein demonstrates the design, synthesis, invivo, invitro and in silico studies of steroidal 5and#945;-Reductase inhibitors as potential candidates for the treatment of Benign Prostatic Hyperplasia. Different aliphatic and aromatic p-substituted esters of 5and#945;, 6and#946;-dibromo/dichloro-17-Oxoandrostan-3and#946;-yl esters (ND-1 to ND-25) and 16-formyl-17-chloroandrosta-5,16 diene esters (ND-26to ND-31) have been synthesised. newline