22-azido-6β-methoxy-3α,5-cyclo-5α-23,24-bisnorcholane | 331869-35-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 22-azido-6β-methoxy-3α,5-cyclo-5α-23,24-bisnorcholane
• 英文别名: (20S)-6β-methoxy-20-(azidomethyl)-3α,5-cyclo-5α-pregnane；(1S,2R,5R,7R,8R,10S,11S,14R,15S)-14-[(2S)-1-azidopropan-2-yl]-8-methoxy-2,15-dimethylpentacyclo[8.7.0.02,7.05,7.011,15]heptadecane
• CAS: 331869-35-3
• 化学式: C₂₃H₃₇N₃O
• 分子量: 371.566
• InChiKey: ZHRKTGDQTAOOHR-WGRYGTHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  22-azido-6β-methoxy-3α,5-cyclo-5α-23,24-bisnorcholane 在 吡啶 、 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 反应 3.0h， 生成 N-[(S)-2-((1aR,3aR,3bS,5aS,6R,8aS,8bS,10R,10aR)-10-Methoxy-3a,5a-dimethyl-hexadecahydro-cyclopenta[a]cyclopropa[2,3]cyclopenta[1,2-f]naphthalen-6-yl)-propyl]-isobutyramide
  参考文献：
  名称：

  Pharmacophore Analysis of the Nuclear Oxysterol Receptor LXRα

  摘要：

  A cell-free assay was developed for the orphan nuclear receptor LXR alpha that measures the ligand-dependent recruitment of a peptide from the steroid receptor coactivator 1 (SRC1) to the nuclear receptor. Using this ligand-sensing assay (LiSA), the structural requirements for activation of the receptor by oxysterols and related compounds were studied. The minimal pharmacophore for receptor activation was shown to be a sterol with a hydrogen bond acceptor at C24. 24(S),25-Epoxycholesterol (1), which meets this criterion, is among the most efficacious of the oxysterols and is an attractive candidate as the LXR alpha natural hormone. Cholenic acid dimethylamide (14) showed increased efficacy compared to 1, whereas the unnatural oxysterol 22(S)-hydroxycholesterol (4) was shown to be an antagonist of 1 in the LiSA. The structural requirements for SRC1 recruitment in the LiSA correlated with the transcriptional activity of compounds in a cell-based reporter assay employing LXR alpha -GAL4 chimeric receptors. Site-directed mutagenesis identified Trp(443) as an amino acid critical for activation of LXR alpha by oxysterol ligands. This information was combined with the structure-activity relationship developed from the LiSA to develop a 3D homology model of LXR alpha. This model may aid the design of synthetic drugs targeted at this transcriptional regulator of cholesterol homeostasis.

  DOI：

  10.1021/jm0004749
• 作为产物：
  描述：

  豆甾醇 在 吡啶 、 sodium tetrahydroborate 、 sodium azide 、 臭氧 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 202.08h， 生成 22-azido-6β-methoxy-3α,5-cyclo-5α-23,24-bisnorcholane
  参考文献：
  名称：

  Synthesis of a Cholesterol Side-Chain Triazole Analogue via ‘Click’ Chemistry

  摘要：

  An efficient preparation of a cholesterol analogue possessing a triazole ring is achieved starting from commercially available stigmasterol. The procedure is based on a [3+2] cycloaddition of a cholesterol possessing a side-chain terminal azide with a terminal acetylene.

  DOI：

  10.1055/s-0034-1381053

文献信息

• Synthesis of a Cholesterol Side-Chain Triazole Analogue via ‘Click’ Chemistry
  作者：Matar Seck、Yagamare Fall、Insa Seck、Alioune Fall、Carmen Lago、Massène Sène、Mohamed Gaye、Generosa Gómez

  DOI：10.1055/s-0034-1381053

  日期：——

  An efficient preparation of a cholesterol analogue possessing a triazole ring is achieved starting from commercially available stigmasterol. The procedure is based on a [3+2] cycloaddition of a cholesterol possessing a side-chain terminal azide with a terminal acetylene.
• Pharmacophore Analysis of the Nuclear Oxysterol Receptor LXRα
  作者：Thomas A. Spencer、Dansu Li、Jonathon S. Russel、Jon L. Collins、Randy K. Bledsoe、Thomas G. Consler、Linda B. Moore、Cristin M. Galardi、David D. McKee、John T. Moore、Michael A. Watson、Derek J. Parks、Millard H. Lambert、Timothy M. Willson

  DOI：10.1021/jm0004749

  日期：2001.3.1

  A cell-free assay was developed for the orphan nuclear receptor LXR alpha that measures the ligand-dependent recruitment of a peptide from the steroid receptor coactivator 1 (SRC1) to the nuclear receptor. Using this ligand-sensing assay (LiSA), the structural requirements for activation of the receptor by oxysterols and related compounds were studied. The minimal pharmacophore for receptor activation was shown to be a sterol with a hydrogen bond acceptor at C24. 24(S),25-Epoxycholesterol (1), which meets this criterion, is among the most efficacious of the oxysterols and is an attractive candidate as the LXR alpha natural hormone. Cholenic acid dimethylamide (14) showed increased efficacy compared to 1, whereas the unnatural oxysterol 22(S)-hydroxycholesterol (4) was shown to be an antagonist of 1 in the LiSA. The structural requirements for SRC1 recruitment in the LiSA correlated with the transcriptional activity of compounds in a cell-based reporter assay employing LXR alpha -GAL4 chimeric receptors. Site-directed mutagenesis identified Trp(443) as an amino acid critical for activation of LXR alpha by oxysterol ligands. This information was combined with the structure-activity relationship developed from the LiSA to develop a 3D homology model of LXR alpha. This model may aid the design of synthetic drugs targeted at this transcriptional regulator of cholesterol homeostasis.