5-环丙基-7-二氟甲基-吡唑[1,5-A]嘧啶-3-羧酸 | 438227-80-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 中文名称: 5-环丙基-7-二氟甲基-吡唑[1,5-A]嘧啶-3-羧酸
• 英文名称: 5-cyclopropyl-7-(difluoromethyl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid
• 英文别名: 5-cyclopropyl-7-difluoromethylpyrazolo[1,5-a]pyrimidine-3-carboxylate
• CAS: 438227-80-6
• 化学式: C₁₁H₉F₂N₃O₂
• mdl: MFCD03075058
• 分子量: 253.208
• InChiKey: AZZCLQRJWLKGDA-UHFFFAOYSA-N

物化性质

• 密度：
  1.74±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  67.5
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  3,4-亚甲二氧基苄胺 、 5-环丙基-7-二氟甲基-吡唑[1,5-A]嘧啶-3-羧酸 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以89%的产率得到N-(benzo[d][1,3]dioxol-5-ylmethyl)-5-cyclopropyl-7-(difluoromethyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide
  参考文献：
  名称：

  Pharmacophore-Based Virtual Screening for Identification of Negative Modulators of GLI1 as Potential Anticancer Agents

  摘要：

  Starting from known GLI1 inhibitors, a pharmacophore-based virtual screening approach was applied to databases of commercially available compounds with the aim of identifying new GLI1 modulators. As a result, three different chemical scaffolds emerged that were characterized by a significant ability to reduce the transcriptional activity of the endogenous Hedgehog-GLI pathway and GLI1 protein level in murine NIH3T3 cells. They also showed a micromolar antiproliferative activity in human melanoma (A375) and medulloblastoma (DAOY) cell lines, without cytotoxicity in non-neoplastic mammary epithelial cells.

  DOI：

  10.1021/acsmedchemlett.9b00639
• 作为产物：
  描述：

  1-cyclopropyl-4,4-difluorobutane-1,3-dione 在 水 、 溶剂黄146 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 11.0h， 生成 5-环丙基-7-二氟甲基-吡唑[1,5-A]嘧啶-3-羧酸
  参考文献：
  名称：

  5-二氟甲基和7-二氟甲基取代的吡唑并[1,5-a]嘧啶的区域选择性合成

  摘要：

  3,4-取代的5-氨基吡唑与含有二氟甲基的不对称1,3-二羰基化合物在乙酸中环缩合生成7-二氟甲基吡唑并[1,5- a ]嘧啶，而5-二氟甲基吡唑并[1,5- a] ]嘧啶衍生物主要在三氟乙酸中形成。

  DOI：

  10.1007/s10593-023-03236-5

文献信息

• Design of pyrazolo-pyrimidines as 11β-HSD1 inhibitors through optimisation of molecular electrostatic potential
  作者：Graeme R. Robb、Scott Boyd、Christopher D. Davies、Alexander G. Dossetter、Frederick W. Goldberg、Paul D. Kemmitt、James S. Scott、John G. Swales

  DOI：10.1039/c5md00043b

  日期：——

  Rapid and efficient lead optimisation through quantification of the molecular electrostatic potential using quantum mechanics.

  通过量子力学对分子电荷势进行定量化，实现快速高效的铅优化。
• Discovery, Structure–Activity Relationship, and Biological Evaluation of Noninhibitory Small Molecule Chaperones of Glucocerebrosidase
  作者：Samarjit Patnaik、Wei Zheng、Jae H. Choi、Omid Motabar、Noel Southall、Wendy Westbroek、Wendy A. Lea、Arash Velayati、Ehud Goldin、Ellen Sidransky、William Leister、Juan J. Marugan

  DOI：10.1021/jm300063b

  日期：2012.6.28

  A major challenge in the field of Gaucher disease has been the development of new therapeutic strategies including molecular chaperones. All previously described chaperones of glucocerebrosidase are enzyme inhibitors, which complicates their clinical development because their chaperone activity must be balanced against the functional inhibition of the enzyme. Using a novel high throughput screening methodology, we identified a chemical series that does not inhibit the enzyme but can still facilitate its translocation to the lysosome as measured by immunostaining of glucocerebrosidase in patient fibroblasts. These compounds provide the basis for the development of a novel approach toward small molecule treatment for patients with Gaucher disease.
• Pharmacophore-Based Virtual Screening for Identification of Negative Modulators of GLI1 as Potential Anticancer Agents
  作者：Fabrizio Manetti、Barbara Stecca、Roberta Santini、Luisa Maresca、Giuseppe Giannini、Maurizio Taddei、Elena Petricci

  DOI：10.1021/acsmedchemlett.9b00639

  日期：2020.5.14

  Starting from known GLI1 inhibitors, a pharmacophore-based virtual screening approach was applied to databases of commercially available compounds with the aim of identifying new GLI1 modulators. As a result, three different chemical scaffolds emerged that were characterized by a significant ability to reduce the transcriptional activity of the endogenous Hedgehog-GLI pathway and GLI1 protein level in murine NIH3T3 cells. They also showed a micromolar antiproliferative activity in human melanoma (A375) and medulloblastoma (DAOY) cell lines, without cytotoxicity in non-neoplastic mammary epithelial cells.