(20S,25R)-2-methylene-19,26-dinor-22-(E)-ene-1α,25-dihydroxyvitamin D3 | 1204226-30-1

• 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: (20S,25R)-2-methylene-19,26-dinor-22-(E)-ene-1α,25-dihydroxyvitamin D3
• 英文别名: (1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(E,2S,6R)-6-hydroxyhept-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol
• CAS: 1204226-30-1
• 化学式: C₂₆H₄₀O₃
• 分子量: 400.602
• InChiKey: OSYUVBVMUWQGDB-MONDEBEWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 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：

  (8S,20S)-des-A,B-8-benzoyloxy-20-[(4'R)-(tertbutyldimethylsilyl)oxy-pent-(1'E)-en-yl]-pregnane 在 重铬酸吡啶 、 氢氟酸 、 4-甲基苯磺酸吡啶 、 苯基锂 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 二丁醚 、 水 、 乙腈 为溶剂， 反应 50.5h， 生成 (20S,25R)-2-methylene-19,26-dinor-22-(E)-ene-1α,25-dihydroxyvitamin D3
  参考文献：
  名称：

  26-Desmethyl-2-methylene-22-ene-19-nor-1α,25-dihydroxyvitamin D3 compounds selectively active on intestine

  摘要：

  Six new analogs of 2-methylene-19-nor-1 alpha,25-dihydroxyvitamin D-3, 6-7 and 8a,b-9a,b, have been synthesized. All compounds are characterized by a trans double bond located in the side chain between C-22 and C-23. While compounds 6 and 7 possess C-26 and C-27 methyls, compounds 8a,b and 9a,b lack one of these groups. A Lythgoe-based synthesis, employing the Wittig-Horner reaction was used for these preparations. Two different types of Delta E-22-25-hydroxy Grundmann's ketone, having either only one stereogenic center located at position C-20 (20 and 21), or two stereogenic centers located at 20- and 25-positions (24a,b-25a,b) were obtained by a multi-step procedure from commercial vitamin D-2. The introduction of a double bond at C-22 appeared to lower biological activity in vitro and in vivo. Further removal of a 26-methyl in these analogs had little effect on receptor binding, HL-60 differentiation and CYP24A expression but markedly diminished or eliminated in vivo activity on bone calcium mobilization while retaining activity on intestinal calcium transport. (C) 2014 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2014.01.012

文献信息

• 2-Methylene-19,26-Dinor-(20S,22E,25R)-Vitamin D Analogs
  申请人：DeLuca Hector F.

  公开号：US20100009947A1

  公开（公告）日：2010-01-14

  This invention discloses 2-methylene-19,26-dinor-(20S,22E,25R)-vitamin D analogs, and specifically 2-methylene-19,26-dinor-(20S,22E,25R)-1α,25-dihydroxyvitamin D 3 , and pharmaceutical uses therefor. This compound exhibits transcription activity as well as pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus 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. This compound also shows no activity in vivo on bone calcium mobilization and relatively low intestinal calcium transport activity compared to the native hormone 1α,25-dihydroxyvitamin D 3 , and therefore may be used to treat autoimmune disorders or inflammatory diseases in humans as well as renal osteodystrophy. This compound may also be used for the treatment or prevention of obesity.

  该发明披露了2-亚甲基-19,26-去甲-(20S,22E,25R)-维生素D类似物，具体为2-亚甲基-19,26-去甲-(20S,22E,25R)-1α,25-二羟基维生素D3，以及其药用用途。该化合物表现出转录活性，以及在阻止未分化细胞增殖和诱导它们分化为单核细胞方面表现出显著活性，因此可作为抗癌剂和用于治疗银屑病等皮肤疾病以及皱纹、松弛皮肤、干燥皮肤和皮脂分泌不足等皮肤状况的药物。该化合物在体内对骨钙动员没有活性，与天然激素1α,25-二羟基维生素D3相比，肠钙运输活性相对较低，因此可用于治疗人类的自身免疫性疾病或炎症性疾病，以及肾性骨病。该化合物还可用于治疗或预防肥胖症。
• US8399439B2
  申请人：——

  公开号：US8399439B2

  公开（公告）日：2013-03-19
• [EN] 2-METHYLENE-19, 26-DINOR-(20S, 22E, 25R)-VITAMIN D ANALOGS<br/>[FR] ANALOGUES DE LA 2-MÉTHYLÈNE-19,26-DINOR-(20S,22E,25R)-VITAMINE D
  申请人：WISCONSIN ALUMNI RES FOUND

  公开号：WO2010006169A2

  公开（公告）日：2010-01-14

  This invention discloses 2-methylene-19,26-dinor-(20S,22E,25R)- vitamin D analogs, and specifically 2-methylene-19,26-dinor-(20S,22E,25R)-lα,25- dihydroxyvitamin D3, and pharmaceutical uses therefor. This compound exhibits transcription activity as well as pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus 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. This compound also shows no activity in vivo on bone calcium mobilization and relatively low intestinal calcium transport activity compared to the native hormone lα,25-dihydroxyvitamin D3, and therefore may be used to treat autoimmune disorders or inflammatory diseases in humans as well as renal osteodystrophy. This compound may also be used for the treatment or prevention of obesity.