tert-butyl ((3R)-1-(6-bromo-3-(2-cyanobenzyl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl)piperidin-3-yl)carbamate | 1377432-86-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: tert-butyl ((3R)-1-(6-bromo-3-(2-cyanobenzyl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl)piperidin-3-yl)carbamate
• 英文别名: tert-butyl N-[(3R)-1-[6-bromo-3-[(2-cyanophenyl)methyl]-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-2-yl]piperidin-3-yl]carbamate
• CAS: 1377432-86-4
• 化学式: C₂₄H₂₇BrN₆O₃
• 分子量: 527.421
• InChiKey: HJDQOFBBWVVRMP-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl ((3R)-1-(6-bromo-3-(2-cyanobenzyl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl)piperidin-3-yl)carbamate 在 三氟乙酸 、 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 以92%的产率得到2-((2-((R)-3-aminopiperidin-1-yl)-6-bromo-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-3(7H)-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：

  2,4-二氯-7H吡咯[2,3-D]嘧啶 在 4-二甲氨基吡啶 、 N-溴代丁二酰亚胺(NBS) 、 sodium hydride 、 碳酸氢钠 、 potassium carbonate 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.33h， 生成 tert-butyl ((3R)-1-(6-bromo-3-(2-cyanobenzyl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl)piperidin-3-yl)carbamate
  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