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コムロ アキヒコ
KOMURO AKIHIKO
小室 晃彦 所属 新潟薬科大学 薬学部 薬学科 職種 教授 |
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| 言語種別 | 英語 |
| 発行・発表の年月 | 2019/06 |
| 形態種別 | 論文 |
| 査読 | 査読あり |
| 標題 | Structural requirements of cholenamide derivatives as the LXR ligands. |
| 執筆形態 | 共著 |
| 掲載誌名 | Bioorganic & medicinal chemistry letters |
| 掲載区分 | 国外 |
| 巻・号・頁 | 29(11),pp.1330-1335 |
| 著者・共著者 | Saida-Tamiya Kana, Tamiya Minoru, Sekiya Genki, Isobe Kazunori, Kitazawa Takaaki, Isaka Nobuhisa, Matsukawa Ayako, Kawahara Kohichi, Komuro Akihiko, Ishiguro Masaji |
| 概要 | A study of the structural requirements of cholic acid derivatives as liver X receptor (LXR) ligands was performed. A model of cholenamide derivative 1 complexed with LXR showed that the C24 carbonyl oxygen forms a hydrogen bond with His435 located close to Trp457. The N,N-dimethyl group is located in a hydrophobic pocket. Based on these data, we designed compounds with high affinity for LXRs. Cholenamide derivatives 1-11 were synthesized from 3β-acetyl-Δ5-cholenic acid 20, and lactams 12-19 were synthesized from alcohol 25. Tertiary amides 3 and 4 showed higher activity in reporter assays, and compounds with hydrophobic residues exhibited the highest activity of all derivatives. The stereochemistry at C23 was found to be an important determinant of EC50 and gene transactivation, as each isomer exhibited different activity. |
| DOI | 10.1016/j.bmcl.2019.03.051 |
| ISSN | 1464-3405 |
| PMID | 30952591 |