1α,25-dihydroxy-24-oxo-16-ene-20-cyclopropyl-vitamin D3 | 1143517-37-6

• 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: 1α,25-dihydroxy-24-oxo-16-ene-20-cyclopropyl-vitamin D3
• 英文别名: 1alpha,25(OH)2-24-oxo-16-ene-20-cyclopropyl-vitamin D3；1-[1-[(3aS,4E,7aS)-4-[(2Z)-2-[(3S,5R)-3,5-dihydroxy-2-methylidenecyclohexylidene]ethylidene]-7a-methyl-3a,5,6,7-tetrahydro-3H-inden-1-yl]cyclopropyl]-4-hydroxy-4-methylpentan-3-one
• CAS: 1143517-37-6
• 化学式: C₂₈H₄₀O₄
• 分子量: 440.623
• InChiKey: JKRFMOIIMQLASH-RFTHJHCXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  77.8
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1α,3β-di(tert-butyl-dimethyl-silanyloxy)-25-trimethylsilanyloxy-16-ene-20-cyclopropyl-24-oxo-cholecalciferol 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 40.0h， 以85%的产率得到1α,25-dihydroxy-24-oxo-16-ene-20-cyclopropyl-vitamin D3
  参考文献：
  名称：

  Synthesis and Anti-inflammatory Properties of 1α,25-Dihydroxy-16-ene-20-cyclopropyl-24-oxo-vitamin D₃, a Hypocalcemic, Stable Metabolite of 1α,25-Dihydroxy-16-ene-20-cyclopropyl-vitamin D₃

  摘要：

  1 alpha,25(OH)(2)-16-ene-20-cyclopropyl-vitamin D-3 (13) is several fold more potent than the natural hormone 1 alpha,25-dihydroxyvitamin D-3 (1) as an anti-infilammatory agent. Here, we have further analyzed the anti-inflammatory properties of 13, confirming it as the most potent analogue tested within this family. We then determined the structures of all the natural metabolites of 13, including the 24-oxo metabolite 14, and carried out its synthesis. A comparison of 13 with 14 showed a similar induction of the primary VDR target genes CYP24A1 and CAMP and comparable anti-inflammatory properties as revealed by a similar inhibition of TNF-alpha, IL-12/23p40, IL-6, and IFN-gamma production. Interestingly, 14 displays a 3-fold lower calcemic activity in vivo compared to 13. Collectively, these findings indicate that the strong potency of 13 can be explained by the accumulation of its stable 24-oxo metabolite, which shows immunoregulatory and anti-inflammatory properties superimposable, to those exerted by 13 itself.

  DOI：

  10.1021/jm801365a

文献信息

• Synthesis and Anti-inflammatory Properties of 1α,25-Dihydroxy-16-ene-20-cyclopropyl-24-<i>oxo</i>-vitamin D₃, a Hypocalcemic, Stable Metabolite of 1α,25-Dihydroxy-16-ene-20-cyclopropyl-vitamin D₃
  作者：Gilles Laverny、Giuseppe Penna、Milan Uskokovic、Stanislaw Marczak、Hubert Maehr、Pawel Jankowski、Caroline Ceailles、Paul Vouros、Brenden Smith、Matthew Robinson、G. Satyanarayana Reddy、Luciano Adorini

  DOI：10.1021/jm801365a

  日期：2009.4.23

  1 alpha,25(OH)(2)-16-ene-20-cyclopropyl-vitamin D-3 (13) is several fold more potent than the natural hormone 1 alpha,25-dihydroxyvitamin D-3 (1) as an anti-infilammatory agent. Here, we have further analyzed the anti-inflammatory properties of 13, confirming it as the most potent analogue tested within this family. We then determined the structures of all the natural metabolites of 13, including the 24-oxo metabolite 14, and carried out its synthesis. A comparison of 13 with 14 showed a similar induction of the primary VDR target genes CYP24A1 and CAMP and comparable anti-inflammatory properties as revealed by a similar inhibition of TNF-alpha, IL-12/23p40, IL-6, and IFN-gamma production. Interestingly, 14 displays a 3-fold lower calcemic activity in vivo compared to 13. Collectively, these findings indicate that the strong potency of 13 can be explained by the accumulation of its stable 24-oxo metabolite, which shows immunoregulatory and anti-inflammatory properties superimposable, to those exerted by 13 itself.