β.-D-核-六吡喃糖,1,6-脱水-3-脱氧-2-O-甲基-4-O-(四氢-2-呋喃基)甲基- | 71971-31-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并三嗪类
• 中文名称: β.-D-核-六吡喃糖,1,6-脱水-3-脱氧-2-O-甲基-4-O-(四氢-2-呋喃基)甲基-
• 英文名称: 7-methylpyrrolo[2,1-f][1,2,4]triazine-2,4(1H,3H)-dione
• 英文别名: 7-Methylpyrrol<2,1-f>-1,2,4-triazin-2,4-(1H,3H)dion；7-methyl-1H-pyrrolo[2,1-f][1,2,4]triazine-2,4-dione；7-methyl-1H-pyrrolo[2,1-f][1,2,4]triazine-2,4-dione
• CAS: 71971-31-8
• 化学式: C₇H₇N₃O₂
• 分子量: 165.151
• InChiKey: IUDZVMAVOPKMLT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  63.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  β.-D-核-六吡喃糖,1,6-脱水-3-脱氧-2-O-甲基-4-O-(四氢-2-呋喃基)甲基- 在 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 24.0h， 以2 g的产率得到2,4-dichloro-7-methylpyrrolo[2,1-f][1,2,4]triazine
  参考文献：
  名称：

  Pyrimidinone Nicotinamide Mimetics as Selective Tankyrase and Wnt Pathway Inhibitors Suitable for in Vivo Pharmacology

  摘要：

  The canonical Wnt pathway plays an important role in embryonic development, adult tissue homeostasis, and cancer. Germ line mutations of several Wnt pathway components, such as Axin, APC, and beta-catenin, can lead to oncogenesis. Inhibition of the poly(ADP-ribose) polymerase (PARE)) catalytic domain of the tankyrases (TNKS1 and TNKS2) is known to inhibit the Wnt pathway via increased stabilization of Axin. In order to explore the consequences of tankyrase and Wnt pathway inhibition in preclinical models of cancer and its impact on normal tissue, we sought a small molecule inhibitor of TNKS1/2 with suitable physicochemical properties and pharmacokinetics for hypothesis testing in vivo. Starting from a 2-phenyl quinazolinone hit (compound 1), we discovered the pyrrolopyrimidinone compound 25 (AZ6102), which is a potent TNKS1/2 inhibitor that has 100 fold selectivity against other PARP family enzymes and shows 5 nM Wnt pathway inhibition in DLD-1 cells. Moreover, compound 25 can be formulated well in a clinically relevant intravenous solution at 20 mg/mL, has demonstrated good pharmacokinetics in preclinical species, and shows low Caco2 efflux to avoid possible tumor resistance mechanisms.

  DOI：

  10.1021/ml5003663
• 作为产物：
  描述：

  7-methylpyrrolo<2,1-f>-1,2,4-triazine-2,4-(1H,3H)-dione-5-carboxylic acid 生成 β.-D-核-六吡喃糖,1,6-脱水-3-脱氧-2-O-甲基-4-O-(四氢-2-呋喃基)甲基-
  参考文献：
  名称：

  MIGLIARA O.; PETRISO S.; SPRIO V., J. HETEROCYCL. CHEM., 1979, 16, NO 5, 833-834

  摘要：

  DOI：