benzyl 4-(2,4-dichlorophenyl)-6-(2-(dimethylamino)-2-oxoethyl)-2-methyl-5-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]-pyridine-3-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: benzyl 4-(2,4-dichlorophenyl)-6-(2-(dimethylamino)-2-oxoethyl)-2-methyl-5-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]-pyridine-3-carboxylate
• 英文别名: benzyl 4-(2,4-dichlorophenyl)-6-[2-(dimethylamino)-2-oxoethyl]-2-methyl-5-oxo-7H-pyrrolo[3,4-b]pyridine-3-carboxylate
• 化学式: C₂₆H₂₃Cl₂N₃O₄
• 分子量: 512.392
• InChiKey: DGROEWJPQLDJHT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  79.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzyl 4-(2,4-dichlorophenyl)-6-(2-(dimethylamino)-2-oxoethyl)-2-methyl-5-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]-pyridine-3-carboxylate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 以100%的产率得到4-(2,4-Dichlorophenyl)-6-[2-(dimethylamino)-2-oxoethyl]-6,7-dihydro-2-methyl-5-oxo-5H-pyrrolo[3,4-b]pyridine-3-carboxylic acid
  参考文献：
  名称：

  Optimization of Activity, Selectivity, and Liability Profiles in 5-Oxopyrrolopyridine DPP4 Inhibitors Leading to Clinical Candidate (Sa)-2-(3-(Aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-5H-pyrrolo[3,4-b]pyridin-6(7H)-yl)-N,N-dimethylacetamide (BMS-767778)

  摘要：

  Optimization of a 5-oxopyrrolopyridine series based upon structure activity relationships (SARs) developed from our previous efforts on a number of related bicyclic series yielded compound 2s (BMS-767778) with an overall activity, selectivity, efficacy, PK, and developability profile suitable for progression into the clinic. SAR in the series and characterization of 2s are described.

  DOI：

  10.1021/jm4008906
• 作为产物：
  描述：

  乙酰丙酮苄酯 在 ammonium acetate 、 硝酸 、 溶剂黄146 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基乙酰胺 、 水 、 异丙醇 为溶剂， 反应 112.83h， 生成 benzyl 4-(2,4-dichlorophenyl)-6-(2-(dimethylamino)-2-oxoethyl)-2-methyl-5-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]-pyridine-3-carboxylate
  参考文献：
  名称：

  Optimization of Activity, Selectivity, and Liability Profiles in 5-Oxopyrrolopyridine DPP4 Inhibitors Leading to Clinical Candidate (Sa)-2-(3-(Aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-5H-pyrrolo[3,4-b]pyridin-6(7H)-yl)-N,N-dimethylacetamide (BMS-767778)

  摘要：

  Optimization of a 5-oxopyrrolopyridine series based upon structure activity relationships (SARs) developed from our previous efforts on a number of related bicyclic series yielded compound 2s (BMS-767778) with an overall activity, selectivity, efficacy, PK, and developability profile suitable for progression into the clinic. SAR in the series and characterization of 2s are described.

  DOI：

  10.1021/jm4008906

文献信息

• Optimization of Activity, Selectivity, and Liability Profiles in 5-Oxopyrrolopyridine DPP4 Inhibitors Leading to Clinical Candidate (<i>Sa</i>)-2-(3-(Aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-5<i>H</i>-pyrrolo[3,4-<i>b</i>]pyridin-6(7<i>H</i>)-yl)-<i>N</i>,<i>N</i>-dimethylacetamide (BMS-767778)
  作者：Pratik Devasthale、Ying Wang、Wei Wang、John Fevig、JianXin Feng、Aiying Wang、Tom Harrity、Don Egan、Nathan Morgan、Michael Cap、Aberra Fura、Herbert E. Klei、Kevin Kish、Carolyn Weigelt、Lucy Sun、Paul Levesque、Frederic Moulin、Yi-Xin Li、Robert Zahler、Mark S. Kirby、Lawrence G. Hamann

  DOI：10.1021/jm4008906

  日期：2013.9.26

  Optimization of a 5-oxopyrrolopyridine series based upon structure activity relationships (SARs) developed from our previous efforts on a number of related bicyclic series yielded compound 2s (BMS-767778) with an overall activity, selectivity, efficacy, PK, and developability profile suitable for progression into the clinic. SAR in the series and characterization of 2s are described.