3β-cholestanyl 2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl-(1->3)-2,4,6-tri-O-acetyl-α-D-mannopyranosyl-(1->3)-2,4,6-tri-O-acetyl-α-D-mannopyranosyl-(1->2)-3,4,6-tri-O-acetyl-α-D-mannopyranoside | 1144492-05-6

• 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: 3β-cholestanyl 2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl-(1->3)-2,4,6-tri-O-acetyl-α-D-mannopyranosyl-(1->3)-2,4,6-tri-O-acetyl-α-D-mannopyranosyl-(1->2)-3,4,6-tri-O-acetyl-α-D-mannopyranoside
• 英文别名: 3β-cholestanyl 2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl-(1-3)-2,4,6-tri-O-acetyl-α-D-mannopyranosyl-(1-2)-3,4,6-tri-O-acetyl-α-D-mannopyranoside
• CAS: 1144492-05-6
• 化学式: C₆₅H₉₈O₂₆
• 分子量: 1295.48
• InChiKey: QLKROBDGSNWTDF-CJJJIPAUSA-N

物化性质

• 沸点：
  1021.4±65.0 °C(predicted)
• 密度：
  1.26±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.65
• 重原子数：
  91.0
• 可旋转键数：
  24.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  318.38
• 氢给体数：
  0.0
• 氢受体数：
  26.0

反应信息

• 作为反应物：
  描述：

  3β-cholestanyl 2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl-(1->3)-2,4,6-tri-O-acetyl-α-D-mannopyranosyl-(1->3)-2,4,6-tri-O-acetyl-α-D-mannopyranosyl-(1->2)-3,4,6-tri-O-acetyl-α-D-mannopyranoside 在 sodium methylate 作用下， 以 甲醇 为溶剂， 以96%的产率得到3β-cholestanyl α-D-mannopyranosyl-(1-3)-α-D-mannopyranosyl-(1-2)-α-D-mannopyranoside
  参考文献：
  名称：

  Discovery of PG545: A Highly Potent and Simultaneous Inhibitor of Angiogenesis, Tumor Growth, and Metastasis

  摘要：

  Increasing the aglycone lipophilicity of a series of polysulfated oligosaccharide glycoside heparan sulfate (HS) mimetics via attachment of a steroid or long chain alkyl group resulted in compounds with significantly improved in vitro and ex vivo antiangiogenic activity. The compounds potently inhibited heparanase and HS-binding angiogenic growth factors and displayed improved antitumor and antimetastatic activity in vivo compared with the earlier series. Preliminary pharmacokinetic analyses also revealed significant increases in half-life following iv dosing, ultimately supporting less frequent dosing regimens in preclinical tumor models compared with other HS mimetics. The compounds also displayed only mild anticoagulant activity, a common side effect usually associated with HS mimetics. These efforts led to the identification of 3 beta-cholestanyl 2,3,4,6-tetra-O-sulfo-alpha-D-glucopyranosyl- (1 -> 4)-2,3,6-tri-O-sulfo-alpha-D-glucopyranosyl-(1 -> 4)-2,3,6-tri-O-sulfo-alpha-D-glucopyranosyl-(1 -> 4)-2,3,6-tri-O-sulfo-beta-D-glucopyranoside, tridecasodium salt (PG545, 18) as a clinical candidate. Compound 18 was recently evaluated in a phase I clinical trial in cancer patients.

  DOI：

  10.1021/jm201708h
• 作为产物：
  描述：

  C₄₀H₅₂Cl₃NO₂₆ 、 3β-胆甾烷醇 在 三氟甲磺酸三甲基硅酯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以58%的产率得到3β-cholestanyl 2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl-(1->3)-2,4,6-tri-O-acetyl-α-D-mannopyranosyl-(1->3)-2,4,6-tri-O-acetyl-α-D-mannopyranosyl-(1->2)-3,4,6-tri-O-acetyl-α-D-mannopyranoside
  参考文献：
  名称：

  Discovery of PG545: A Highly Potent and Simultaneous Inhibitor of Angiogenesis, Tumor Growth, and Metastasis

  摘要：

  Increasing the aglycone lipophilicity of a series of polysulfated oligosaccharide glycoside heparan sulfate (HS) mimetics via attachment of a steroid or long chain alkyl group resulted in compounds with significantly improved in vitro and ex vivo antiangiogenic activity. The compounds potently inhibited heparanase and HS-binding angiogenic growth factors and displayed improved antitumor and antimetastatic activity in vivo compared with the earlier series. Preliminary pharmacokinetic analyses also revealed significant increases in half-life following iv dosing, ultimately supporting less frequent dosing regimens in preclinical tumor models compared with other HS mimetics. The compounds also displayed only mild anticoagulant activity, a common side effect usually associated with HS mimetics. These efforts led to the identification of 3 beta-cholestanyl 2,3,4,6-tetra-O-sulfo-alpha-D-glucopyranosyl- (1 -> 4)-2,3,6-tri-O-sulfo-alpha-D-glucopyranosyl-(1 -> 4)-2,3,6-tri-O-sulfo-alpha-D-glucopyranosyl-(1 -> 4)-2,3,6-tri-O-sulfo-beta-D-glucopyranoside, tridecasodium salt (PG545, 18) as a clinical candidate. Compound 18 was recently evaluated in a phase I clinical trial in cancer patients.

  DOI：

  10.1021/jm201708h

文献信息

• [EN] NOVEL SULFATED OLIGOSACCHARIDE DERIVATIVES<br/>[FR] NOUVEAUX DÉRIVÉS D'OLIGOSACCHARIDES SULFATÉS
  申请人：PROGEN PHARMACEUTICALS LTD

  公开号：WO2009049370A1

  公开（公告）日：2009-04-23

  The invention relates to novel compounds that have utility as inhibitors of heparan sulfate-binding proteins; compositions comprising the compounds, and use of the compounds and compositions thereof for the antiangiogenic, antimetastatic, anti-inflammatory, antimicrobial, anticoagulant and/or antithrombotic treatment of a mammalian subject.

  这项发明涉及具有作为肝素硫酸结合蛋白抑制剂的效用的新化合物；包含这些化合物的组合物；以及利用这些化合物和组合物对哺乳动物主体进行抗血管生成、抗转移、抗炎、抗微生物、抗凝血和/或抗血栓治疗的用途。