3-azidopropyl 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 | 1144491-74-6

• 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-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: 3-azidoprop-1-yl 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；[(2R,3R,4S,5S,6S)-3,4-diacetyloxy-6-(3-azidopropoxy)-5-[(2R,3S,4S,5R,6R)-3,5-diacetyloxy-6-(acetyloxymethyl)-4-[(2R,3S,4S,5R,6R)-3,5-diacetyloxy-6-(acetyloxymethyl)-4-[(2R,3S,4S,5R,6R)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxan-2-yl]oxyoxan-2-yl]oxyoxan-2-yl]oxyoxan-2-yl]methyl acetate
• CAS: 1144491-74-6
• 化学式: C₅₃H₇₃N₃O₃₄
• 分子量: 1296.16
• InChiKey: SKJSSROZBJLCMW-SGOOJZKKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  90
• 可旋转键数：
  41
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  430
• 氢给体数：
  0
• 氢受体数：
  36

反应信息

• 作为反应物：
  描述：

  3-azidopropyl 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 三苯基膦树脂 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 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-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)-1,3,4,6-tetra-O-acetyl-D-mannopyranose 在 三氟化硼乙醚 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 5.0h， 以61%的产率得到3-azidopropyl 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：

  聚硫寡糖苷作为血管生成和肿瘤生长抑制剂的合成及生物学评价

  摘要：

  合成了一系列包含α（1→3）/α（1→2）连接的甘露糖残基的多硫酸化五糖和四糖苷，作为硫酸乙酰肝素（HS）模拟物，并评估了它们抑制血管生成的能力。这些化合物与血管生成生长因子（FGF-1，FGF-2和VEGF）紧密结合，并强烈抑制乙酰肝素酶活性。另外，该化合物在基于细胞的和离体测定中显示出有效的指示血管生成的活性，四糖显示出与五糖相当的活性。所选化合物还在对III期HS模拟1耐药的小鼠黑色素瘤（实体瘤）模型中显示出良好的体内抗肿瘤活性。（muparfostat，以前称为PI-88）。亲脂性修饰还导致抗凝活性降低，HS模拟物的常见副作用，并赋予了大鼠合理的药代动力学特征，例如硫酸辛基四糖5。数据支持对该类化合物作为潜在的抗血管生成，抗癌治疗剂的进一步研究。

  DOI：

  10.1021/jm901449m

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.