2018年
Novel androgen receptor full antagonists: Design, synthesis, and a docking study of glycerol and aminoglycerol derivatives that contain p-carborane cages
Bioorganic and Medicinal Chemistry
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- 巻
- 26
- 号
- 13
- 開始ページ
- 3805
- 終了ページ
- 3811
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.bmc.2018.06.007
- 出版者・発行元
- Elsevier Ltd
Based on the co-crystal structure of bicalutamide with a T877A-mutated androgen receptor (AR), glycerol and aminoglycerol derivatives were designed and synthesized as a novel type of carborane-containing AR modulators. The (R)-isomer of 6c, whose chirality is derived from the glycerol group, showed 20 times more potent cell inhibitory activity against LNCaP cell lines expressing T877A-mutated AR than the corresponding (S)-isomer. Docking studies of both isomers with AR suggested that (R)-6c is in closer spatial proximity to helix-12 of the AR than (S)-6c, which is the most important common motif in the secondary structure of AR for the expression of antagonistic activity.
- リンク情報
- ID情報
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- DOI : 10.1016/j.bmc.2018.06.007
- ISSN : 1464-3391
- ISSN : 0968-0896
- eISSN : 1464-3391
- PubMed ID : 29903411
- SCOPUS ID : 85048273192