(20R)-des-A,B-20-[(4'S)-(tert-butyldimethylsilyl)oxy-pentyl]-pregnan-8-one | 946132-21-4

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: (20R)-des-A,B-20-[(4'S)-(tert-butyldimethylsilyl)oxy-pentyl]-pregnan-8-one
• 英文别名: (20R)-de-A,B-20-[(4S)-tert-butyldimethylsilyloxy-pentyl]pregnan-8-one；(1R,3aR,7aR)-1-[(2R,6S)-6-[tert-butyl(dimethyl)silyl]oxyheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-one
• CAS: 946132-21-4
• 化学式: C₂₃H₄₄O₂Si
• 分子量: 380.687
• InChiKey: RGFYJCLRXPBTJM-MRXSCTINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.99
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (20R)-des-A,B-20-[(4'S)-(tert-butyldimethylsilyl)oxy-pentyl]-pregnan-8-one 在 苯基锂 作用下， 以 四氢呋喃 、 二丁醚 为溶剂， 反应 21.5h， 以71%的产率得到(20R,25S)-1α-[(tert-butyldimethylsilyl)oxy]-2-methylene-25-[(tert-butyldimethylsilyl)oxy]-19,26-dinorvitamin D3 tert-butyldimethylsilyl ether
  参考文献：
  名称：

  VITAMIN D ANALOG - NEL, METHODS AND USES THEREOF

  摘要：

  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。

  公开号：

  US20070191316A1
• 作为产物：
  描述：

  (8S,20S)-des-A,B-8-benzoyloxy-20-(hydroxymethyl)-pregnane 在 2,6-二甲基吡啶 、 正丁基锂 、 四丙基高钌酸铵 、 乙醇 、 palladium 10% on activated carbon 、 氢气 、 三氧化硫吡啶 、 N-甲基吗啉氧化物 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 43.0h， 生成 (20R)-des-A,B-20-[(4'S)-(tert-butyldimethylsilyl)oxy-pentyl]-pregnan-8-one
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm1010447

文献信息

• 2alpha-Methyl and 2beta-Methyl Analogs of 19,26-Dinor-1alpha,25-Dihydroxyvitamin D3 and Their Uses
  申请人：DeLuca Hector F.

  公开号：US20120283228A1

  公开（公告）日：2012-11-08

  This invention discloses 2α-methyl and 2β-methyl analogs of 19,26-dinor-1α,25-dihydroxyvitamin D 3 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.

  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。
• 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.
• 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。