3-[(2S)-2-[(3S,5R,6R,8S,9S,10R,13S,14S,17R)-5,6-dihydroxy-10,13-dimethyl-3-(2-morpholin-4-yl-2-oxoethoxy)-1,2,3,4,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]propyl]-1,1-dimethylurea | 1620077-98-6

• 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: 3-[(2S)-2-[(3S,5R,6R,8S,9S,10R,13S,14S,17R)-5,6-dihydroxy-10,13-dimethyl-3-(2-morpholin-4-yl-2-oxoethoxy)-1,2,3,4,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]propyl]-1,1-dimethylurea
• CAS: 1620077-98-6
• 化学式: C₃₁H₅₃N₃O₆
• 分子量: 563.778
• InChiKey: VWXNDAQYWCQZPX-WOJMBDDJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  40
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  、 二甲氨基甲酰氯 在 4-二甲氨基吡啶 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 以51%的产率得到3-[(2S)-2-[(3S,5R,6R,8S,9S,10R,13S,14S,17R)-5,6-dihydroxy-10,13-dimethyl-3-(2-morpholin-4-yl-2-oxoethoxy)-1,2,3,4,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]propyl]-1,1-dimethylurea
  参考文献：
  名称：

  Structure–activity relationships of oxysterol-derived pharmacological chaperones for Niemann–Pick type C1 protein

  摘要：

  Niemann-Pick disease type C is a fatal neurodegenerative disease, and its major cause is mutations in NPC1 gene. This gene encodes NPC1 protein, a late endosomal polytopic membrane protein required for intracellular cholesterol trafficking. One prevalent mutation (11061T) has been shown to cause a folding defect, which results in failure of endosomal localization of the protein, leading to loss-of-function phenotype. We have previously demonstrated that several oxysterols and their derivatives act as pharmacological chaperones; binding of these compounds to NPC1(11061T) mutant protein corrects the localization/maturation defect of the mutant protein. Here, we disclose detailed structure-activity relationships of oxysterol derivatives as pharmacological chaperones for NPC1(11061T) mutant. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.05.064

文献信息

• Structure–activity relationships of oxysterol-derived pharmacological chaperones for Niemann–Pick type C1 protein
  作者：Kenji Ohgane、Fumika Karaki、Tomomi Noguchi-Yachide、Kosuke Dodo、Yuichi Hashimoto

  DOI：10.1016/j.bmcl.2014.05.064

  日期：2014.8

  Niemann-Pick disease type C is a fatal neurodegenerative disease, and its major cause is mutations in NPC1 gene. This gene encodes NPC1 protein, a late endosomal polytopic membrane protein required for intracellular cholesterol trafficking. One prevalent mutation (11061T) has been shown to cause a folding defect, which results in failure of endosomal localization of the protein, leading to loss-of-function phenotype. We have previously demonstrated that several oxysterols and their derivatives act as pharmacological chaperones; binding of these compounds to NPC1(11061T) mutant protein corrects the localization/maturation defect of the mutant protein. Here, we disclose detailed structure-activity relationships of oxysterol derivatives as pharmacological chaperones for NPC1(11061T) mutant. (C) 2014 Elsevier Ltd. All rights reserved.