Design, synthesis and evaluation of novel 16-imidazolyl substituted steroidal derivatives possessing potent diversified pharmacological properties

作者：Bansal Ranju^*; Guleria Sheetal; Thota Sridhar; Bodhankar Subhash L; Patwardhan Moreshwar R; Zimmer Christina; Hartmann Rolf W; Harvey Alan L

来源：Steroids, 2012, 77(6): 621-629.

DOI：10.1016/j.steroids.2012.02.005

• 16-Imidazolyl steroids
• Aromatase inhibitors
• Bis-quaternary steroids
• Skeletal muscle relaxants
• Anticholinesterases

As a part of our investigations into the structural-activity relationship studies of a novel class of medicinally active 16-substituted steroids, several new 16-imidazolyl substituted steroidal derivatives have been synthesized and pharmacologically evaluated in the current study. The new steroidal analogues 5, 6, 8, 9, 11 and 12 exhibited moderate cytotoxic effects in sixty cancer cell lines derived from nine cancers types. The imidazolyl substituted steroidal derivatives 6 (DPJ-RG-1241) and 7 (RB-401) were obtained as the powerful inhibitors of aromatase with IC50= 0.18 mu M and IC50= 0.168 mu M, respectively, approximately 1.2 and 1.4 times more potent in comparison to standard drug exemestane. The bis-quaternary steroids 13 and 14 displayed potent skeletal muscle relaxant properties. An affinity constant of 0.007 mu M was observed for compound 14 on frog rectus abdominis muscle preparation and 13 displayed a very high anticholinesterase activity K-i= 25 nM, approximately 115-fold higher in comparison to standard drug galanthamine (K-i = 2.9 mu M).

• 出版日期2012-5