2-Methylene-(20R,25S)-19,26-dinor-1alpha,25-dihydroxyvitamin D3

• 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: 2-Methylene-(20R,25S)-19,26-dinor-1alpha,25-dihydroxyvitamin D3
• 英文别名: (20R,25S)-2-methylene-19,26-dinor-1α,25-dihydroxyvitamin D3；(1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R,6S)-6-hydroxyheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol
• 化学式: C₂₆H₄₂O₃
• 分子量: 402.618
• InChiKey: SWWBPPHPGINSED-VXCBRZSCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• 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

• 作为反应物：
  描述：

  2-Methylene-(20R,25S)-19,26-dinor-1alpha,25-dihydroxyvitamin D3 在 Wilkinson's catalyst 氢气 作用下， 以 苯 为溶剂， 反应 4.0h， 以29%的产率得到(20R,25S)-2α-methyl-19,26-dinor-1α,25-dihydroxyvitamin D3
  参考文献：
  名称：

  2alpha-Methyl and 2beta-Methyl Analogs of 19,26-Dinor-1alpha,25-Dihydroxyvitamin D3 and Their Uses

  摘要：

  这项发明揭示了19,26-去甲基-1α,25-二羟基维生素D3的2α-甲基和2β-甲基类似物以及其药用。这些化合物在体外表现出生物活性，可作为抗癌剂以及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用途。这些化合物在体内几乎没有钙调节活性，因此可用于治疗人类的自身免疫性疾病，以及继发性甲状旁腺功能亢进和肾性骨病。

  公开号：

  US20120283228A1
• 作为产物：
  描述：

  [2-[(3'R,5'R)-3',5'-bis[(tert-butyldimethylsilyl)oxy]-4'-methylenecyclohexylidene]ethyl]diphenylphosphine oxide 在 氢氟酸 、 苯基锂 作用下， 以 四氢呋喃 、 二丁醚 、 水 、 乙腈 为溶剂， 反应 29.5h， 生成 2-Methylene-(20R,25S)-19,26-dinor-1alpha,25-dihydroxyvitamin D3
  参考文献：
  名称：

  2alpha-Methyl and 2beta-Methyl Analogs of 19,26-Dinor-1alpha,25-Dihydroxyvitamin D3 and Their Uses

  摘要：

  这项发明揭示了19,26-去甲基-1α,25-二羟基维生素D3的2α-甲基和2β-甲基类似物以及其药用。这些化合物在体外表现出生物活性，可作为抗癌剂以及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用途。这些化合物在体内几乎没有钙调节活性，因此可用于治疗人类的自身免疫性疾病，以及继发性甲状旁腺功能亢进和肾性骨病。

  公开号：

  US20120283228A1

文献信息

• VITAMIN D ANALOG - NEL, METHODS AND USES THEREOF
  申请人：DELUCA Hector F.

  公开号：US20070191316A1

  公开（公告）日：2007-08-16

  Compounds of formula IA or IB are provided where X 1 , X 2 and X 3 are independently selected from H or hydroxy protecting groups and R 1 is selected from straight or branched chain alkyl groups having from 1 to 8 carbon atoms; straight or branched chain alkenyl groups having from 2 to 8 carbon atoms; straight or branched chain hydroxy-substituted alkyl groups having from 1 to 8 carbon atoms; straight and branched chain hydroxy-substituted alkenyl groups having from 2 to 8 carbon atoms. Such compounds are used in preparing pharmaceutical compositions and are useful in treating a variety of biological conditions.

  提供了公式为IA或IB的化合物，其中X1、X2和X3独立地选自H或羟基保护基团，R1选自直链或支链烷基，其碳原子数为1至8；直链或支链烯基，其碳原子数为2至8；直链或支链羟基取代的烷基，其碳原子数为1至8；直链和支链羟基取代的烯基，其碳原子数为2至8。这些化合物用于制备药物组合物，并且在治疗各种生物条件方面非常有用。
• Removal of the 26-Methyl Group from 19-nor-1α,25-Dihydroxyvitamin D₃ Markedly Reduces in Vivo Calcemic Activity without Altering in Vitro VDR Binding, HL-60 Cell Differentiation, and Transcription
  作者：Pawel Grzywacz、Grazia Chiellini、Lori A. Plum、Margaret Clagett-Dame、Hector F. DeLuca

  DOI：10.1021/jm1010447

  日期：2010.12.23

  Twelve new analogues of 19-nor-1 alpha,25-dihydroxyvitamin D-3 (5-16) were prepared by convergent syntheses, employing the Wittig-Horner reaction. The necessary Grundmann type ketones (45-48), possessing fixed configurations of the hydroxyl group at C-25, were obtained by a multistep procedure from commercial vitamin D-2 and enantiomers of 1,3-butanediol (23 and 24). We have examined the influence of removal of one of the methyl groups located at C-25 on the biological in vitro and in vivo activity. The in vivo tests showed that the synthesized vitamin D compounds (5-16) exhibit reduced calcemic activity both in bone and in the intestine. However, in vitro potency of 2-methylene and 2 alpha-methyl compounds (5-10, 13, and 14) remained similar or enhanced as compared to that of 1 alpha,25-(OH)(2)D-3.
• (20R,25S)-2-Methylene-19,26-Dinor-1alpha,25-Dihydroxyvitamin D3 in Crystalline Form
  申请人：DeLuca Hector F.

  公开号：US20120083614A1

  公开（公告）日：2012-04-05

  A method of purifying (20R,25S)-2-methylene-19,26-dinor-1α,25-dihydroxyvitamin D 3 to obtain (20R,25S)-2-methylene-19,26-dinor-1α,25-dihydroxyvitamin D 3 in crystalline form. The method includes the steps of preparing a solvent of methanol and water, dissolving a product containing (20R,25S)-2-methylene-19,26-dinor-1α,25-dihydroxyvitamin D 3 to be purified in the solvent, cooling the solvent and dissolved product below ambient temperature for a sufficient amount of time to form a precipitate of (20R,25S)-2-methylene-19,26-dinor-1α,25-dihydroxyvitamin D 3 crystals, and recovering the (20R,25S)-2-methylene-19,26-dinor-1α,25-dihydroxyvitamin D 3 crystals.
• US7528122B2
  申请人：——

  公开号：US7528122B2

  公开（公告）日：2009-05-05
• US8404874B2
  申请人：——

  公开号：US8404874B2

  公开（公告）日：2013-03-26