2-((2-chloro-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-3-yl)methyl)benzonitrile | 1355174-84-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 2-((2-chloro-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-3-yl)methyl)benzonitrile
• 英文别名: 2-[(2-chloro-6-methyl-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-3-yl)methyl]benzonitrile
• CAS: 1355174-84-3
• 化学式: C₁₅H₁₁ClN₄O
• 分子量: 298.732
• InChiKey: UURWWFLLJISXSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  72.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(R)-aminopiperidine dihydrochloride 、 2-((2-chloro-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-3-yl)methyl)benzonitrile 在 碳酸氢钠 作用下， 以 乙醇 为溶剂， 反应 6.0h， 以72%的产率得到2-((2-((R)-3-aminopiperidin-1-yl)-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-3-yl)methyl)benzonitrile
  参考文献：
  名称：

  Novel pyrrolopyrimidine analogues as potent dipeptidyl peptidase IV inhibitors based on pharmacokinetic property-driven optimization

  摘要：

  We previously reported a highly potent DPP-IV inhibitor 6 with low in vivo efficacy. While trying to maintain consistent in vitro and in vivo biological activity, we initiated a pharmacokinetic property-driven optimization to improve the metabolic stability and permeability of inhibitor 6. A simple scaffold replacement of thienopyrimidine with pyrrolopyrimidine (21a) led to significantly improved metabolic stability (4% vs. 65% remaining). Further modification of the pyrrolopyrimidine scaffold to produce compound 21j resulted in much better oral bioavailability than 6. Importantly, compound 21j exhibits greater in vivo efficacy than does 6 and Alogliptin and is worthy of further development. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.03.015
• 作为产物：
  描述：

  6-methyl-7H-pyrrolo[2,3-d]pyrimidine-2,4-diol 在 4-二甲氨基吡啶 、 sodium hydride 、 三乙胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 0.83h， 生成 2-((2-chloro-6-methyl-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-3-yl)methyl)benzonitrile
  参考文献：
  名称：

  Novel pyrrolopyrimidine analogues as potent dipeptidyl peptidase IV inhibitors based on pharmacokinetic property-driven optimization

  摘要：

  We previously reported a highly potent DPP-IV inhibitor 6 with low in vivo efficacy. While trying to maintain consistent in vitro and in vivo biological activity, we initiated a pharmacokinetic property-driven optimization to improve the metabolic stability and permeability of inhibitor 6. A simple scaffold replacement of thienopyrimidine with pyrrolopyrimidine (21a) led to significantly improved metabolic stability (4% vs. 65% remaining). Further modification of the pyrrolopyrimidine scaffold to produce compound 21j resulted in much better oral bioavailability than 6. Importantly, compound 21j exhibits greater in vivo efficacy than does 6 and Alogliptin and is worthy of further development. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.03.015