tert-butyl ((3R)-1-(3-(2-cyanobenzyl)-4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-2-yl)piperidin-3-yl)carbamate | 1377432-84-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: tert-butyl ((3R)-1-(3-(2-cyanobenzyl)-4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-2-yl)piperidin-3-yl)carbamate
• 英文别名: tert-butyl N-[(3R)-1-[3-[(2-cyanophenyl)methyl]-4-oxo-5H-pyrrolo[3,2-d]pyrimidin-2-yl]piperidin-3-yl]carbamate
• CAS: 1377432-84-2
• 化学式: C₂₄H₂₈N₆O₃
• 分子量: 448.525
• InChiKey: NUHYGLKSQQXDIQ-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  33
• 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-(3-(2-cyanobenzyl)-4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-2-yl)piperidin-3-yl)carbamate 在 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 叔丁胺 作用下， 以 二氯甲烷 、 水 、 异丙醇 为溶剂， 反应 4.0h， 生成 tert-butyl ((3R)-1-(3-(2-cyanobenzyl)-4-oxo-7-(pyridin-4-yl)-4,5-dihydro-3H-pyrrolo[3,2-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
• 作为产物：
  描述：

  6-甲基尿嘧啶 在 4-二甲氨基吡啶 、 硫酸 、 硝酸 、 sodium hydride 、 碳酸氢钠 、 potassium carbonate 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 、 锌 、 三氯氧磷 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 、 甲苯 为溶剂， 反应 7.33h， 生成 tert-butyl ((3R)-1-(3-(2-cyanobenzyl)-4-oxo-4,5-dihydro-3H-pyrrolo[3,2-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