1,2-dideoxy-α-D-glucopyranoside[1,2-d]-2-heptylsulfanyl-1,3-oxazoline | 1384841-09-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1,2-dideoxy-α-D-glucopyranoside[1,2-d]-2-heptylsulfanyl-1,3-oxazoline
• 英文别名: (3aS,5R,6S,7S,7aR)-2-heptylsulfanyl-5-(hydroxymethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[2,3-d][1,3]oxazole-6,7-diol
• CAS: 1384841-09-1
• 化学式: C₁₄H₂₅NO₅S
• 分子量: 319.422
• InChiKey: XIVKTZYSNYPLEF-LBELIVKGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  117
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3,4,6-tri-O-acetyl-1,2-dideoxy-α-D-glucopyranoside[1,2-d]-2-heptylsulfanyl-1,3-oxazoline 在 甲醇 、 sodium methylate 作用下， 反应 0.5h， 以89%的产率得到1,2-dideoxy-α-D-glucopyranoside[1,2-d]-2-heptylsulfanyl-1,3-oxazoline
  参考文献：
  名称：

  Conformationally-Locked N-Glycosides with Selective β-Glucosidase Inhibitory Activity: Identification of a New Non-Iminosugar-Type Pharmacological Chaperone for Gaucher Disease

  摘要：

  A series of conformationally locked N-glycosides having a cis-1,2-fused pyranose-1,3-oxazoline-2-thione structure and bearing different substituents at the exocyclic sulfur has been prepared. The polyhydroxylated bicyclic system was built in only three steps by treatment of the corresponding readily available 1,2-anhydrosugar with KSCN using TiO(TFA)(2) as catalyst, followed by S-alkylation and acetyl deprotection. In vitro screening against several glycosidase enzymes showed highly specific inhibition of mammalian beta-glucosidase with a marked dependence of the potency upon the nature of the exocyclic substituent. The most potent representative, bearing an S-(omega-hydroxyhexadecyl) substituent, was further assayed as inhibitor of the human lysosomal beta-glucocerebrosidase and as pharmacological chaperone in Gaucher disease fibroblasts. Activity enhancements in N370S/N370S mutants analogous to those achieved with the reference compound ambroxol were attained with a more favorable chaperone/inhibitor balance.

  DOI：

  10.1021/jm3006178

文献信息

• Conformationally-Locked <i>N</i>-Glycosides with Selective β-Glucosidase Inhibitory Activity: Identification of a New Non-Iminosugar-Type Pharmacological Chaperone for Gaucher Disease
  作者：Javier Castilla、Rocío Rísquez、Deysi Cruz、Katsumi Higaki、Eiji Nanba、Kousaku Ohno、Yoshiyuki Suzuki、Yolanda Díaz、Carmen Ortiz Mellet、José M. García Fernández、Sergio Castillón

  DOI：10.1021/jm3006178

  日期：2012.8.9

  A series of conformationally locked N-glycosides having a cis-1,2-fused pyranose-1,3-oxazoline-2-thione structure and bearing different substituents at the exocyclic sulfur has been prepared. The polyhydroxylated bicyclic system was built in only three steps by treatment of the corresponding readily available 1,2-anhydrosugar with KSCN using TiO(TFA)(2) as catalyst, followed by S-alkylation and acetyl deprotection. In vitro screening against several glycosidase enzymes showed highly specific inhibition of mammalian beta-glucosidase with a marked dependence of the potency upon the nature of the exocyclic substituent. The most potent representative, bearing an S-(omega-hydroxyhexadecyl) substituent, was further assayed as inhibitor of the human lysosomal beta-glucocerebrosidase and as pharmacological chaperone in Gaucher disease fibroblasts. Activity enhancements in N370S/N370S mutants analogous to those achieved with the reference compound ambroxol were attained with a more favorable chaperone/inhibitor balance.