(20R)-2-methylene-19,26,27-trinor-1α,25-dihydroxycalciferol

• 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-dihydroxycalciferol
• 英文别名: (1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R)-6-hydroxyhexan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol
• 化学式: C₂₅H₄₀O₃
• 分子量: 388.591
• InChiKey: YKAGNRTWXXOESX-LQGIGFFQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.76
• 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：

  (20R)-2-methylene-19,26,27-trinor-1α,25-dihydroxycalciferol 在 Wilkinson's catalyst 氢气 作用下， 以 苯 为溶剂， 反应 4.0h， 以36%的产率得到(20R)-2-methylene-19,26,27-trinor-1α-hydroxyvitamin D₃
  参考文献：
  名称：

  2-Substituted-1Alpha,25-Dihydroxy-19,26,27-Trinor Vitamin D Analogs and Uses Thereof

  摘要：

  提供了I、II或III式化合物，其中X1、X2和X3独立地选择自H和羟基保护基团，R1和R2独立地选择自具有1至8个碳原子的直链或支链烷基基团、具有2至8个碳原子的直链或支链烯基基团、具有1至8个碳原子的直链或支链羟基取代烷基基团或具有2至8个碳原子的直链和支链羟基取代烯基基团；而R3独立地选择自具有1至8个碳原子的直链或支链烷基基团、具有2至8个碳原子的直链或支链烯基基团、具有1至8个碳原子的直链或支链羟基取代烷基基团或具有2至8个碳原子的直链和支链羟基取代烯基基团。这些化合物用于制备药物组合物，并且在治疗各种生物状况方面非常有用。

  公开号：

  US20070238704A1
• 作为产物：
  描述：

  (S)-2-((3R,3aR,7S,7aR)-octahydro-7-hydroxy-3a-methyl-1H-inden-3-yl)propyl 4-methylbenzenesulfonate 在 吡啶 、 lithium aluminium tetrahydride 、 pyridinium dichromate 、 nickel(II) chloride hexahydrate 、 氢氟酸 、 4-甲基苯磺酸吡啶 、 苯基锂 、 三乙胺 、 potassium iodide 、 锌 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 环己烷 、 水 、 丙酮 、 乙腈 为溶剂， 反应 71.0h， 生成 (20R)-2-methylene-19,26,27-trinor-1α,25-dihydroxycalciferol
  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

• 2-Substituted-1Alpha,25-Dihydroxy-19,26,27-Trinor Vitamin D Analogs and Uses Thereof
  申请人：DeLuca F. Hector

  公开号：US20070238704A1

  公开（公告）日：2007-10-11

  Compounds of formula I, II or III are provided where X 1 , X 2 and X 3 are independently selected from H and hydroxy protecting groups and R 1 and R 2 are independently selected from H or 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, or straight and branched chain hydroxy-substituted alkenyl groups having from 2 to 8 carbon atoms; and R 3 is independently 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, or 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I、II或III式化合物，其中X1、X2和X3独立地选择自H和羟基保护基团，R1和R2独立地选择自具有1至8个碳原子的直链或支链烷基基团、具有2至8个碳原子的直链或支链烯基基团、具有1至8个碳原子的直链或支链羟基取代烷基基团或具有2至8个碳原子的直链和支链羟基取代烯基基团；而R3独立地选择自具有1至8个碳原子的直链或支链烷基基团、具有2至8个碳原子的直链或支链烯基基团、具有1至8个碳原子的直链或支链羟基取代烷基基团或具有2至8个碳原子的直链和支链羟基取代烯基基团。这些化合物用于制备药物组合物，并且在治疗各种生物状况方面非常有用。
• (20R)-2a-Methyl-19,26,27-Trinor-Vitamin D Analogs
  申请人：DeLuca Hector F.

  公开号：US20080300223A1

  公开（公告）日：2008-12-04

  This invention discloses (20R)-2α-methyl-19,26,27-trinor-vitamin D analogs, and specifically (20R)-2α-methyl-19,26,27-trinor-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 very low activity in vivo on bone calcium mobilization and 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.
• US8193169B2
  申请人：——

  公开号：US8193169B2

  公开（公告）日：2012-06-05
• US8404666B2
  申请人：——

  公开号：US8404666B2

  公开（公告）日：2013-03-26
• [EN] 2- SUBSTITUTED-1ALPHA, 25-DIHYDROXY-19,26,27-TRINOR VITAMIN D ANALOGS AND USES THEREOF<br/>[FR] ANALOGUES DE LA 1ALPHA,25-DIHYDROXY-19,26,27-TRINOR VITAMINE D SUBSTITUÉE EN POSITION 2 ET LEURS UTILISATIONS
  申请人：WISCONSIN ALUMNI RES FOUND

  公开号：WO2008035228A2

  公开（公告）日：2008-03-27

  [EN] Compounds of Formula (I), (II) or (III) are provided where X₁, X₂ and X₃ are independently selected from H and hydroxy protecting groups and R₁ and R₂ are independently selected from H or 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, or straight and branched chain hydroxy-substituted alkenyl groups having from 2 to 8 carbon atoms; and R₃ is independently 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, or 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.
  [FR] L'invention concerne des composés représentés par la Formule (I), (II) ou (III) où X₁, X₂ et X₃ sont choisis indépendamment parmi H et les groupes protecteurs d'hydroxy et R₁ et R₂ sont indépendamment choisis parmi H ou les groupes alkyle à chaîne droite ou ramifiée ayant de 1 à 8 atomes de carbone, les groupes alcényle à chaîne droite ou ramifiée ayant de 2 à 8 atomes de carbone, les groupes alkyle substitués par un hydroxy à chaîne droite ou ramifiée ayant de 1 à 8 atomes de carbone, ou les groupes alcényle substitués par hydroxy à chaîne droite et ramifiée ayant de 2 à 8 atomes de carbone; et R₃ est indépendamment choisi parmi des groupes alkyle à chaîne droite ou ramifiée ayant de 1 à 8 atomes de carbone, les groupes alcényle à chaîne droite ou ramifiée ayant de 2 à 8 atomes de carbone, les groupes alkyle substitués par hydroxy à chaîne droite ou ramifiée ayant de 1 à 8 atomes de carbone, ou des groupes alcényle substitués par hydroxy à chaîne droite et ramifiée ayant de 2 à 8 atomes de carbone. De tels composés sont utilisés dans la préparation de compositions pharmaceutiques et sont utiles dans le traitement d'une diversité de conditions biologiques.