(S)-2-(3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-5H-pyrrolo[3,4-b]pyridin-6(7H)-yl)-N-methyl-N-propylacetamide trifluoroacetic acid salt

• 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: (S)-2-(3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-5H-pyrrolo[3,4-b]pyridin-6(7H)-yl)-N-methyl-N-propylacetamide trifluoroacetic acid salt
• 英文别名: 2-[3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-7H-pyrrolo[3,4-b]pyridin-6-yl]-N-methyl-N-propylacetamide;2,2,2-trifluoroacetic acid
• 化学式: C₂HF₃O₂*C₂₁H₂₄Cl₂N₄O₂
• 分子量: 549.377
• InChiKey: HOXFVRMNMNEWKZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.28
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  3-benzyl 5-ethyl 6-(chloromethyl)-4-(2,4-dichlorophenyl)-2-methylpyridine-3,5-dicarboxylate 在 sodium tetrahydroborate 、 palladium 10% on activated carbon 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氨 、 氢气 、 碳酸氢钠 、 甲基磺酰氯 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 异丙醇 为溶剂， 反应 8.33h， 生成 (S)-2-(3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-5H-pyrrolo[3,4-b]pyridin-6(7H)-yl)-N-methyl-N-propylacetamide trifluoroacetic acid salt
  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.