tert-butyl (S)-(4-(4-(bis(4-fluorophenyl)methyl)-1,4-diazepan-1-yl)-1-(isoindolin-2-yl)-1,4-dioxobutan-2-yl)carbamate | 1351231-46-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl (S)-(4-(4-(bis(4-fluorophenyl)methyl)-1,4-diazepan-1-yl)-1-(isoindolin-2-yl)-1,4-dioxobutan-2-yl)carbamate
• 英文别名: tert-butyl N-[(2S)-4-[4-[bis(4-fluorophenyl)methyl]-1,4-diazepan-1-yl]-1-(1,3-dihydroisoindol-2-yl)-1,4-dioxobutan-2-yl]carbamate
• CAS: 1351231-46-3
• 化学式: C₃₅H₄₀F₂N₄O₄
• 分子量: 618.724
• InChiKey: QLMPOCREIAQHTO-PMERELPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  45
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  82.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl (S)-(4-(4-(bis(4-fluorophenyl)methyl)-1,4-diazepan-1-yl)-1-(isoindolin-2-yl)-1,4-dioxobutan-2-yl)carbamate 、 三氟乙酸 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 (S)-2-amino-4-(4-(bis(4-fluorophenyl)methyl)-1,4-diazepan-1-yl)-1-(isoindolin-2-yl)butane-1,4-dione bis(2,2,2-trifluoroacetate)
  参考文献：
  名称：

  Structure–Activity Relationship Studies on Isoindoline Inhibitors of Dipeptidyl Peptidases 8 and 9 (DPP8, DPP9): Is DPP8-Selectivity an Attainable Goal?

  摘要：

  This work represents the first directed study to identify modification points in the topology of a representative DPP8/9-inhibitor, capable of rendering selectivity for DPP8 over DPP9. The availability of a DPP8-selective compound would be highly instrumental for studying and untwining the biological roles of DPP8 and DPP9 and for the disambiguation of biological effects of nonselective DPP-inhibitors that have mainly been ascribed to blocking of DPPIV's action. The cell-permeable DPP8/9-inhibitor 7 was selected as a lead and dissected into several substructures that were modified separately for evaluating their potential to contribute to selectivity. The obtained results, together with earlier work from our group, clearly narrow down the most probable DPP8-selectivity imparting modification points in DPP8/9 inhibitors to parts of space that are topologically equivalent to the piperazine ring system in 7. This information can be considered of high value for future design of compounds with maximal DPP8 selectivity.

  DOI：

  10.1021/jm200383j
• 作为产物：
  描述：

  Boc-L-天冬氨酸 4-甲酯 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 potassium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 tert-butyl (S)-(4-(4-(bis(4-fluorophenyl)methyl)-1,4-diazepan-1-yl)-1-(isoindolin-2-yl)-1,4-dioxobutan-2-yl)carbamate
  参考文献：
  名称：

  Structure–Activity Relationship Studies on Isoindoline Inhibitors of Dipeptidyl Peptidases 8 and 9 (DPP8, DPP9): Is DPP8-Selectivity an Attainable Goal?

  摘要：

  This work represents the first directed study to identify modification points in the topology of a representative DPP8/9-inhibitor, capable of rendering selectivity for DPP8 over DPP9. The availability of a DPP8-selective compound would be highly instrumental for studying and untwining the biological roles of DPP8 and DPP9 and for the disambiguation of biological effects of nonselective DPP-inhibitors that have mainly been ascribed to blocking of DPPIV's action. The cell-permeable DPP8/9-inhibitor 7 was selected as a lead and dissected into several substructures that were modified separately for evaluating their potential to contribute to selectivity. The obtained results, together with earlier work from our group, clearly narrow down the most probable DPP8-selectivity imparting modification points in DPP8/9 inhibitors to parts of space that are topologically equivalent to the piperazine ring system in 7. This information can be considered of high value for future design of compounds with maximal DPP8 selectivity.

  DOI：

  10.1021/jm200383j

文献信息

• Structure–Activity Relationship Studies on Isoindoline Inhibitors of Dipeptidyl Peptidases 8 and 9 (DPP8, DPP9): Is DPP8-Selectivity an Attainable Goal?
  作者：Sebastiaan Van Goethem、Veerle Matheeussen、Jurgen Joossens、Anne-Marie Lambeir、Xin Chen、Ingrid De Meester、Achiel Haemers、Koen Augustyns、Pieter Van der Veken

  DOI：10.1021/jm200383j

  日期：2011.8.25

  This work represents the first directed study to identify modification points in the topology of a representative DPP8/9-inhibitor, capable of rendering selectivity for DPP8 over DPP9. The availability of a DPP8-selective compound would be highly instrumental for studying and untwining the biological roles of DPP8 and DPP9 and for the disambiguation of biological effects of nonselective DPP-inhibitors that have mainly been ascribed to blocking of DPPIV's action. The cell-permeable DPP8/9-inhibitor 7 was selected as a lead and dissected into several substructures that were modified separately for evaluating their potential to contribute to selectivity. The obtained results, together with earlier work from our group, clearly narrow down the most probable DPP8-selectivity imparting modification points in DPP8/9 inhibitors to parts of space that are topologically equivalent to the piperazine ring system in 7. This information can be considered of high value for future design of compounds with maximal DPP8 selectivity.