(25R)-25-(1-adamantyl)-1α,25-dihydroxy-2-methylidene-23,23,24,24-tetradehydro-19,26,27-trinorvitamin D3 | 1395789-27-1

• 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: (25R)-25-(1-adamantyl)-1α,25-dihydroxy-2-methylidene-23,23,24,24-tetradehydro-19,26,27-trinorvitamin D3
• 英文别名: (1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R,6R)-6-(1-adamantyl)-6-hydroxyhex-4-yn-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol
• CAS: 1395789-27-1
• 化学式: C₃₅H₅₀O₃
• 分子量: 518.78
• InChiKey: RDOXAQMJPJCGHT-IVTYSHCBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  38
• 可旋转键数：
  4
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  60.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1α-hydroxy-2-methylidene-23,23,24,24-tetradehydro-19,25,26,27-tetranorvitamin D3 1,3-bis(tert-butyldimethylsilyl)ether 在 甲醇 、 正丁基锂 、 dimethyl sulfide borane 、 camphor-10-sulfonic acid 、 戴斯-马丁氧化剂 、 (R)-2-甲基-CBS-恶唑硼烷 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 9.95h， 生成 (25R)-25-(1-adamantyl)-1α,25-dihydroxy-2-methylidene-23,23,24,24-tetradehydro-19,26,27-trinorvitamin D3
  参考文献：
  名称：

  Combination of Triple Bond and Adamantane Ring on the Vitamin D Side Chain Produced Partial Agonists for Vitamin D Receptor

  摘要：

  Vitamin D receptor (VDR) ligands are therapeutic agents that are used for the treatment of psoriasis, osteoporosis, and secondary hyperparathyroidism and have immense potential as therapeutic agents for autoimmune diseases, cancers, and cardiovascular diseases. However, the major side effect of VDR ligands, the development of hypercalcemia, limits their expanded use. To develop tissue-selective VDR modulators, we have designed vitamin D analogues with an adamantane ring at the side chain terminal, which would interfere with helix 12, the activation function 2, and modulate the VDR potency. Here we report 25- or 26-adamantyl-23,23,24,24-tetradehydro-19-norvitamin D derivatives (ADTK1-4, 4b,a and 5a,b). These compounds showed high VDR affinities (90% at maximum), partial agonistic activities (EC50 10(-9)-10(-8) M with 40-80% efficacy) in transactivation, and tissue-selective activity in target gene expressions. We investigate the structure-activity relationships of these compounds on the basis of their X-ray crystal structures.

  DOI：

  10.1021/jm401989c

文献信息

• Combination of Triple Bond and Adamantane Ring on the Vitamin D Side Chain Produced Partial Agonists for Vitamin D Receptor
  作者：Takeru Kudo、Michiyasu Ishizawa、Kazuki Maekawa、Makoto Nakabayashi、Yusuke Watarai、Hikaru Uchida、Hiroaki Tokiwa、Teikichi Ikura、Nobutoshi Ito、Makoto Makishima、Sachiko Yamada

  DOI：10.1021/jm401989c

  日期：2014.5.22

  Vitamin D receptor (VDR) ligands are therapeutic agents that are used for the treatment of psoriasis, osteoporosis, and secondary hyperparathyroidism and have immense potential as therapeutic agents for autoimmune diseases, cancers, and cardiovascular diseases. However, the major side effect of VDR ligands, the development of hypercalcemia, limits their expanded use. To develop tissue-selective VDR modulators, we have designed vitamin D analogues with an adamantane ring at the side chain terminal, which would interfere with helix 12, the activation function 2, and modulate the VDR potency. Here we report 25- or 26-adamantyl-23,23,24,24-tetradehydro-19-norvitamin D derivatives (ADTK1-4, 4b,a and 5a,b). These compounds showed high VDR affinities (90% at maximum), partial agonistic activities (EC50 10(-9)-10(-8) M with 40-80% efficacy) in transactivation, and tissue-selective activity in target gene expressions. We investigate the structure-activity relationships of these compounds on the basis of their X-ray crystal structures.