5-isocyanato-1-phenyl-1H-pyrazole | 785781-37-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-isocyanato-1-phenyl-1H-pyrazole
• 英文别名: 5-Isocyanato-1-phenylpyrazole；5-isocyanato-1-phenylpyrazole
• CAS: 785781-37-5
• 化学式: C₁₀H₇N₃O
• 分子量: 185.185
• InChiKey: HAWCTPHYOFYUTG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  47.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (8aS)-2-[(1S,2R)-2-phenylcyclopropyl]tetrahydroimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione hydrochloride 、 5-isocyanato-1-phenyl-1H-pyrazole 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 (8aS)-1,3-dioxo-2-[(1S,2R)-2-phenylcyclopropyl]-N-(1-phenyl-1H-pyrazol-5-yl)hexahydroimidazo[1,5-a]pyrazine-7(1H)-carboxamide
  参考文献：
  名称：

  Identification of MK-5710 ((8aS)-8a-methyl-1,3-dioxo-2-[(1S,2R)-2-phenylcyclo- propyl]-N-(1-phenyl-1H-pyrazol-5-yl)hexahydro-imidazo[1,5-a]pyrazine-7(1H)-carboxamide), a potent smoothened antagonist for use in Hedgehog pathway dependent malignancies, Part 2

  摘要：

  The Hedgehog (Hh-) signaling pathway is a key developmental pathway which gets reactivated in many human tumors, and smoothened (Smo) antagonists are emerging as novel agents for the treatment of malignancies dependent on the Hh-pathway, with the most advanced compounds demonstrating encouraging results in initial clinical trials. A novel series of potent bicyclic hydantoin Smo antagonists was reported in the preceding article, these have been resolved, and optimized to identify potent homochiral derivatives with clean off-target profiles and good pharmacokinetic properties in preclinical species. While showing in vivo efficacy in mouse allograft models, unsubstituted bicyclic tetrahydroimidazo[1,5-a]pyrazine-1,3(2H,5H)-diones were shown to epimerize in plasma. Alkylation of the C-8 position blocks this epimerization, resulting in the identification of MK-5710 (47) which was selected for further development. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.023