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  • 标题:Novel Non-steroidal Progesterone Receptor Ligands Based on m-Carborane Containing a Secondary Alcohol: Effect of Chirality on Ligand Activity
  • 本地全文:下载
  • 作者:Shuichi Mori ; Ryohei Takagaki ; Shinya Fujii
  • 期刊名称:Chemical and Pharmaceutical Bulletin
  • 印刷版ISSN:0009-2363
  • 电子版ISSN:1347-5223
  • 出版年度:2017
  • 卷号:65
  • 期号:11
  • 页码:1051-1057
  • DOI:10.1248/cpb.c17-00544
  • 语种:English
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:

    The progesterone receptor (PR) controls various physiological processes, including the female reproductive system, and nonsteroidal PR ligands are considered to be drug candidates for treatment of various diseases without significant adverse effects. Here, we designed and synthesized m -carborane-based secondary alcohols and investigated their PR-ligand activity. All the synthesized alcohols exhibited PR-antagonistic activity at subnanomolar concentration. Among them, alcohols having a small alkyl side chain and a 4-cyanophenyl group also exhibited PR-agonistic activity in a relatively high concentration range. Optical resolution of secondary alcohols having a methyl side chain was performed, and the PR-ligand activity and PR-binding affinity of the purified enantiomers were examined. The chirality of the secondary alcohol appears to have a more significant influence on PR-agonistic activity than on antagonistic activity.

  • 关键词:progesterone receptor;antagonist;carborane;chirality;lipase
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