| 1373444-45-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• CAS: 1373444-45-1
• 化学式: C₅₂H₆₈Cl₃NO₃₄
• 分子量: 1357.46
• InChiKey: PJGLYZFRKALGRG-NMIMGUBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.04
• 重原子数：
  90.0
• 可旋转键数：
  24.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  439.59
• 氢给体数：
  1.0
• 氢受体数：
  35.0

反应信息

• 作为反应物：
  描述：

  胆固醇 、 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 1.33h， 生成 3β-cholesteryl α-D-mannopyranosyl-(1-3)-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