5α-3β-(3'-hydroxypropyl)cholestane | 158800-53-4

• 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: 5α-3β-(3'-hydroxypropyl)cholestane
• 英文别名: 3-[(3R,5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]propan-1-ol
• CAS: 158800-53-4
• 化学式: C₃₀H₅₄O
• 分子量: 430.758
• InChiKey: UFATVLWNYUPZEF-QYHGRWQDSA-N

物化性质

• 沸点：
  489.3±13.0 °C(predicted)
• 密度：
  0.934±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  10.8
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  5α-3β-(3'-hydroxypropyl)cholestane 在 sodium hydroxide 、 四氯化钛 、 pyridinium chlorochromate 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 9.0h， 生成 5α,3β-[4,4-(3',3"-dicarboxy-5',5'''-(3'''-dicarboxy-5'''-dichloro-4'''-dimethoxybenzyl)-4',4"-dimethoxyphenyl)-buten-3-yl]cholestane
  参考文献：
  名称：

  Synthesis and Anti-HIV Activity of Cosalane Analogues with Substituted Benzoic Acid Rings Attached to the Pharmacophore through Methylene and Amide Linkers

  摘要：

  The cosalane pharmacophore has been extended by the attachment of two additional substituted benzoic acid rings through amide and methylene linkers. The resulting compounds display significant antiviral activity when tested in vitro for inhibition of the cytopathic effects of HIV-1(RF) in CEM-SS cells and HIV-1(IIIB) in MT-4 cells. The compound containing the methylene linker also shows moderate activity versus HIV-2(ROD) in MT-4 cells. Because cosalane and related compounds containing extended pharmacophores inhibit the binding of gp120 to CD4, the presently described new compounds are assumed to act by a similar mechanism. A hypothetical model is proposed for the binding of the methylene-linked compound to CD4.

  DOI：

  10.1021/jo990177f
• 作为产物：
  描述：

  5α-3β-<3'-<(tert-butyldimethylsilyl)oxy>propyl>cholestane 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以88%的产率得到5α-3β-(3'-hydroxypropyl)cholestane
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Cosalane, a Novel Anti-HIV Agent Which Inhibits Multiple Features of Virus Reproduction

  摘要：

  Cosalane (3), a novel anti-HIV agent having a disalicylmethane unit linked to C-3 of cholestane by a three-carbon Linker, was synthesized from commercially available starting materials by a convergent route. Cosalane proved to be a potent inhibitor of HIV with a broad range of activity against a variety of laboratory, drug-resistant, and clinical HIV-1 isolates, HIV-2, and Rauscher murine leukemia virus. The cytotoxicity of cosalane is relatively low as reflected by an in vitro therapeutic index of > 100. Although cosalane inhibits HIV-1 reverse transcriptase and protease, time of addition experiments indicate that it prevents the cytopathic effect of HIV by acting earlier than reverse transcription in the viral replication cycle. The available evidence indicates that the primary mechanism of action of cosalane involves inhibition of gp120-CD4 binding as well as inhibition of a postattachment event prior to reverse transcription.

  DOI：

  10.1021/jm00045a008

文献信息

• Design, Synthesis, and Biological Evaluation of Cosalane, a Novel Anti-HIV Agent Which Inhibits Multiple Features of Virus Reproduction
  作者：Mark Cushman、W. Marek Golebiewski、James B. McMahon、Robert W. Buckheit、David J. Clanton、Owen Weislow、Rudiger D. Haugwitz、John P. Bader、Lisa Graham、William G. Rice

  DOI：10.1021/jm00045a008

  日期：1994.9

  Cosalane (3), a novel anti-HIV agent having a disalicylmethane unit linked to C-3 of cholestane by a three-carbon Linker, was synthesized from commercially available starting materials by a convergent route. Cosalane proved to be a potent inhibitor of HIV with a broad range of activity against a variety of laboratory, drug-resistant, and clinical HIV-1 isolates, HIV-2, and Rauscher murine leukemia virus. The cytotoxicity of cosalane is relatively low as reflected by an in vitro therapeutic index of > 100. Although cosalane inhibits HIV-1 reverse transcriptase and protease, time of addition experiments indicate that it prevents the cytopathic effect of HIV by acting earlier than reverse transcription in the viral replication cycle. The available evidence indicates that the primary mechanism of action of cosalane involves inhibition of gp120-CD4 binding as well as inhibition of a postattachment event prior to reverse transcription.
• Synthesis and Anti-HIV Activity of Cosalane Analogues with Substituted Benzoic Acid Rings Attached to the Pharmacophore through Methylene and Amide Linkers
  作者：Jeffrey A. Ruell、Erik De Clercq、Christophe Pannecouque、Myriam Witvrouw、Tracy L. Stup、Jim A. Turpin、Robert W. Buckheit,、Mark Cushman

  DOI：10.1021/jo990177f

  日期：1999.8.1

  The cosalane pharmacophore has been extended by the attachment of two additional substituted benzoic acid rings through amide and methylene linkers. The resulting compounds display significant antiviral activity when tested in vitro for inhibition of the cytopathic effects of HIV-1(RF) in CEM-SS cells and HIV-1(IIIB) in MT-4 cells. The compound containing the methylene linker also shows moderate activity versus HIV-2(ROD) in MT-4 cells. Because cosalane and related compounds containing extended pharmacophores inhibit the binding of gp120 to CD4, the presently described new compounds are assumed to act by a similar mechanism. A hypothetical model is proposed for the binding of the methylene-linked compound to CD4.