(2R)-3-[[2-(4-chloro-2,5-difluorophenyl)-6-ethylpyrimidin-4-yl]amino]propane-1,2-diol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (2R)-3-[[2-(4-chloro-2,5-difluorophenyl)-6-ethylpyrimidin-4-yl]amino]propane-1,2-diol
• 化学式: C₁₄H₁₁O₃Pol
• 分子量: 343.75
• InChiKey: KPKGFRPQEQJFKH-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  78.3
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2R)-3-[[2-(4-chloro-2,5-difluorophenyl)-6-ethylpyrimidin-4-yl]amino]propane-1,2-diol 、 苯甲醛 在 potassium hydroxide 作用下， 生成
  参考文献：
  名称：

  In silico studies on 2,3-dihydro-1,5-benzothiazepines as cholinesterase inhibitors

  摘要：

  In vitro studies on cholinesterase inhibitory potential on the three sets of 2,3-dihydro-1,5-benzothiazepines have been carried out. The compounds in Set 1 were unsubstituted on ring A, while those in Sets 2 and 3 had a 2'- and 3'-hydoxy substituent, respectively, in ring A. These studies revealed that they are mixed inhibitors of both AChE and BChE as reflected from their IC50 values. It was further observed that 3'-hydroxy substituted benzothiazepines (Set 3) were found to have stronger affinity for both AChE and BChE compared with those of Sets 1 and 2. Moreover, all the compounds in Set 3 were found to be stronger BChE inhibitors than AChE. These experimental observations were rationalized by conducting in silico studies using molecular docking tool of Molecular Operating Environment (MOE) software, thereby, a good correlation was observed between IC50 values and their binding interactions within the enzyme active site. We have observed that these interactions were electrostatic and hydrophobic in nature besides hydrogen bonding. The high BChE inhibitory potential of 3'-hydroxy substituted benzothiazepines was found to be cumulative effect of hydrogen bonding and pi-pi interactions between the ligand and BChE. These findings may serve as a guideline for synthesizing more potent ChE inhibitors for the treatment of Alzheimer's disease and related dementias.

  DOI：

  10.1007/s00044-011-9754-6
• 作为产物：
  描述：

  4-氯-2,5-二氟苯甲酸 在 盐酸 、 ammonium hydroxide 、 氯化亚砜 、 sodium methylate 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 甲醇 、 乙醇 、 氯仿 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 2.5h， 生成 (2R)-3-[[2-(4-chloro-2,5-difluorophenyl)-6-ethylpyrimidin-4-yl]amino]propane-1,2-diol
  参考文献：
  名称：

  发现和生物学评价新型的4-氨基-2-苯基嘧啶衍生物作为有效和口服活性的GPR119激动剂

  摘要：

  合成了新型的4-氨基-2-苯基嘧啶衍生物，并将其评估为GPR119激动剂。优化2-位苯环上的取代基和4-位氨基上的取代基，可以鉴定出显示出强效GPR119激动活性的3,4-二卤代和2,4,5-三卤代苯基衍生物。发现高级类似物（2 R）-3-{[2-（4-氯-2,5-二氟苯基）-6-乙基嘧啶-4-基]氨基}丙烷-1,2-二醇（24g）可以改善在小鼠中口服1 mg / kg的葡萄糖耐量，并在小鼠和猴子中表现出出色的药代动力学特征。在单日治疗一周后，化合物24g在糖尿病kk / Ay小鼠中也显示出优异的抗糖尿病作用。这些结果表明，新型GPR119激动剂24g 不仅可以通过增强葡萄糖依赖性胰岛素的分泌来改善葡萄糖耐受性，还可以通过保留胰腺β细胞功能来改善葡萄糖耐受性。

  DOI：

  10.1016/j.bmc.2012.06.049