(20R)-2-methylene-19,26,27-trinor-1α,25-dihydroxyvitamin D₃ | 1428964-29-7

• 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: (20R)-2-methylene-19,26,27-trinor-1α,25-dihydroxyvitamin D₃
• 英文别名: (1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R)-hexan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol
• CAS: 1428964-29-7
• 化学式: C₂₅H₄₀O₂
• 分子量: 372.591
• InChiKey: PPXATBHVDXKJAT-SKFXDQHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (20R)-2-methylene-19,26,27-trinor-1α,25-dihydroxyvitamin D₃ 在 tris(triphenylphosphine)rhodium(l) chloride 、 氢气 作用下， 以 苯 为溶剂， 反应 4.0h， 以36%的产率得到(20R)-2α-methyl-19,26,27-trinor-1α,25-dihydroxyvitamin D₃
  参考文献：
  名称：

  26- and 27-Methyl groups of 2-substituted, 19-nor-1α,25-dihydroxylated vitamin D compounds are essential for calcium mobilization in vivo

  摘要：

  Twelve new analogs of 19-nor-1 alpha,25-dihydroxyvitamin D-3 6-17, were prepared by a multi-step procedure from known alcohols 18 and 19. We have examined the influence of removing two methyl groups located at C-25, as well as the 25-hydroxy group, on the biological in vitro and in vivo biological activity. Surprisingly, removal of the 26- and 27-methyl groups from either the 2 alpha-methyl or 2-methylene-19-nor-1 alpha,25-dihydroxyvitamin D-3 reduced vitamin D receptor binding, HL-60 differentiation, and 25-hydroxylase transcription in vitro only slightly to moderately (compounds 6-13). However, these compounds were devoid of in vivo bone mobilization activity and had markedly reduced activity on intestinal calcium transport. The analogs 14-17 with a 2 beta-methyl substitution had little or no activity in vitro and in vivo as expected from previous work. (C) 2013 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2013.01.001
• 作为产物：
  描述：

  (8S,20R)-des-A,B-20-[(3'-iso-propoxycarbonyl)propyl]pregnan-8-ol 在 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 、 pyridinium dichromate 、 氢氟酸 、 4-甲基苯磺酸吡啶 、 苯基锂 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 环己烷 、 水 、 乙腈 为溶剂， 反应 73.0h， 生成 (20R)-2-methylene-19,26,27-trinor-1α,25-dihydroxyvitamin D₃
  参考文献：
  名称：

  26- and 27-Methyl groups of 2-substituted, 19-nor-1α,25-dihydroxylated vitamin D compounds are essential for calcium mobilization in vivo

  摘要：

  Twelve new analogs of 19-nor-1 alpha,25-dihydroxyvitamin D-3 6-17, were prepared by a multi-step procedure from known alcohols 18 and 19. We have examined the influence of removing two methyl groups located at C-25, as well as the 25-hydroxy group, on the biological in vitro and in vivo biological activity. Surprisingly, removal of the 26- and 27-methyl groups from either the 2 alpha-methyl or 2-methylene-19-nor-1 alpha,25-dihydroxyvitamin D-3 reduced vitamin D receptor binding, HL-60 differentiation, and 25-hydroxylase transcription in vitro only slightly to moderately (compounds 6-13). However, these compounds were devoid of in vivo bone mobilization activity and had markedly reduced activity on intestinal calcium transport. The analogs 14-17 with a 2 beta-methyl substitution had little or no activity in vitro and in vivo as expected from previous work. (C) 2013 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2013.01.001

文献信息

• [EN] 2a-METHYL AND 2ß-METHYL ANALOGS OF 19,26-DINOR-1a, 25-DIHYDROXYVITAMIN D3 AND THEIR USES<br/>[FR] ANALOGUES 2?-MÉTHYLE ET 2?-MÉTHYLE DE LA 19,26-DINOR-1?,25-DIHYDROXYVITAMINE D3 ET LEURS UTILISATIONS
  申请人：WISCONSIN ALUMNI RES FOUND

  公开号：WO2012151420A1

  公开（公告）日：2012-11-08

  This invention discloses 2α-methyl and 2β-methyl analogs of 19,26-dinor-1α,25-dihydroxyvitamin D3 and pharmaceutical uses therefor. These compounds exhibit in vitro biological activities evidencing use as an anti-cancer agent and for the treatment of skin diseases such as psoriasis as well as skin conditions such as wrinkles, slack skin, dry skin and insufficient sebum secretion. These compounds have little, if any, in vivo calcemic activity and therefore may be used to treat autoimmune disorders in humans as well as secondary hyperparathyroidism and renal osteodystrophy.