3-azidopropyl 2,3,4,6-tetra-O-benzoyl-α-D-glucopyranosyl-(1->4)-2,3,6-tri-O-benzoyl-α-D-glucopyranosyl-(1->4)-2,3,6-tri-O-benzoyl-β-D-glucopyranoside | 1144493-12-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-azidopropyl 2,3,4,6-tetra-O-benzoyl-α-D-glucopyranosyl-(1->4)-2,3,6-tri-O-benzoyl-α-D-glucopyranosyl-(1->4)-2,3,6-tri-O-benzoyl-β-D-glucopyranoside
• 英文别名: 3-azidopropyl 2,3,4,6-tetra-O-benzoyl-α-D-glucopyranosyl-(1-4)-2,3,6-tri-O-benzoyl-α-D-glucopyranosyl-(1-4)-2,3,6-tri-O-benzoyl-β-D-glucopyranoside
• CAS: 1144493-12-8
• 化学式: C₉₁H₇₇N₃O₂₆
• 分子量: 1628.62
• InChiKey: WLRNIVZGOTYREU-UKHJJVOGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.8
• 重原子数：
  120.0
• 可旋转键数：
  32.0
• 环数：
  13.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  367.14
• 氢给体数：
  0.0
• 氢受体数：
  27.0

反应信息

• 作为反应物：
  描述：

  3-azidopropyl 2,3,4,6-tetra-O-benzoyl-α-D-glucopyranosyl-(1->4)-2,3,6-tri-O-benzoyl-α-D-glucopyranosyl-(1->4)-2,3,6-tri-O-benzoyl-β-D-glucopyranoside 在 三苯基膦 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 5.5h， 生成
  参考文献：
  名称：

  [EN] NOVEL SULFATED OLIGOSACCHARIDE DERIVATIVES
  [FR] NOUVEAUX DÉRIVÉS D'OLIGOSACCHARIDES SULFATÉS

  摘要：

  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。

  公开号：

  WO2009049370A1
• 作为产物：
  描述：

  3-叠氮基丙醇 、 2,3,4,6-tetra-O-benzoyl-α-D-glucopyranosyl-(1-4)-2,3,6-tri-O-benzoyl-α-D-glucopyranosyl-(1-4)-2,3,6-tri-O-benzoyl-D-glucopyranosyl trichloroacetimidate 在 三氟甲磺酸三甲基硅酯 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以97%的产率得到3-azidopropyl 2,3,4,6-tetra-O-benzoyl-α-D-glucopyranosyl-(1->4)-2,3,6-tri-O-benzoyl-α-D-glucopyranosyl-(1->4)-2,3,6-tri-O-benzoyl-β-D-glucopyranoside
  参考文献：
  名称：

  [EN] NOVEL SULFATED OLIGOSACCHARIDE DERIVATIVES
  [FR] NOUVEAUX DÉRIVÉS D'OLIGOSACCHARIDES SULFATÉS

  摘要：

  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。

  公开号：

  WO2009049370A1

文献信息

• Discovery of PG545: A Highly Potent and Simultaneous Inhibitor of Angiogenesis, Tumor Growth, and Metastasis
  作者：Vito Ferro、Ligong Liu、Ken D. Johnstone、Norbert Wimmer、Tomislav Karoli、Paul Handley、Jessica Rowley、Keith Dredge、Cai Ping Li、Edward Hammond、Kat Davis、Laura Sarimaa、Job Harenberg、Ian Bytheway

  DOI：10.1021/jm201708h

  日期：2012.4.26

  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.