methyl (1S,3R)-1-(4-bromophenyl)-2-(2-chloroacetyl)-1,3,4,9-tetrahydropyrido[3,4-b]indole-3-carboxylate | 1415726-35-0

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: methyl (1S,3R)-1-(4-bromophenyl)-2-(2-chloroacetyl)-1,3,4,9-tetrahydropyrido[3,4-b]indole-3-carboxylate
• CAS: 1415726-35-0
• 化学式: C₂₁H₁₈BrClN₂O₃
• 分子量: 461.743
• InChiKey: XBQXEZCLJLKIDH-XLIONFOSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  62.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl (1S,3R)-1-(4-bromophenyl)-2-(2-chloroacetyl)-1,3,4,9-tetrahydropyrido[3,4-b]indole-3-carboxylate 、 甲胺 以 甲醇 为溶剂， 反应 16.0h， 以25%的产率得到(2S,8R)-2-(4-bromophenyl)-6-methyl-3,6,17-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),11,13,15-tetraene-4,7-dione
  参考文献：
  名称：

  Exploring the PDE5 H-pocket by ensemble docking and structure-based design and synthesis of novel β-carboline derivatives

  摘要：

  By studying the co-crystal information of interactions between PDE5 and its inhibitors, forty new tetrahydro-beta-carbolines based-analogues were synthesized, and tested for their PDE5 inhibition. Some compounds were as active as tadalafil in inhibiting PDE5 and of better selectivity profile particularly versus PDE11A, the nature of the terminal ring and its nitrogen substituent are the main determinants of selectivity. Ensemble docking confirmed the role of H-loop closed conformer in activity versus its occluded and open forms. Conformational studies showed the effect of bulkiness of the terminal ring N-alkyl substituent on the formation of stable enzyme ligands conformers. The difference in potencies of hydantoin and piperazinedione analogues, together with the necessity of C-5/C-6 R-absolute configuration has been revealed through molecular docking. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.09.029
• 作为产物：
  描述：

  D-色氨酸 在 碳酸氢钠 、 乙酰氯 、 三氟乙酸 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 生成 methyl (1S,3R)-1-(4-bromophenyl)-2-(2-chloroacetyl)-1,3,4,9-tetrahydropyrido[3,4-b]indole-3-carboxylate
  参考文献：
  名称：

  Exploring the PDE5 H-pocket by ensemble docking and structure-based design and synthesis of novel β-carboline derivatives

  摘要：

  By studying the co-crystal information of interactions between PDE5 and its inhibitors, forty new tetrahydro-beta-carbolines based-analogues were synthesized, and tested for their PDE5 inhibition. Some compounds were as active as tadalafil in inhibiting PDE5 and of better selectivity profile particularly versus PDE11A, the nature of the terminal ring and its nitrogen substituent are the main determinants of selectivity. Ensemble docking confirmed the role of H-loop closed conformer in activity versus its occluded and open forms. Conformational studies showed the effect of bulkiness of the terminal ring N-alkyl substituent on the formation of stable enzyme ligands conformers. The difference in potencies of hydantoin and piperazinedione analogues, together with the necessity of C-5/C-6 R-absolute configuration has been revealed through molecular docking. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.09.029

文献信息

• Exploring the PDE5 H-pocket by ensemble docking and structure-based design and synthesis of novel β-carboline derivatives
  作者：Nermin S. Ahmed、Amal H. Ali、Shreen M. El-Nashar、Bernard D. Gary、Alexandra M. Fajardo、Heather N. Tinsley、Gary A. Piazza、Matthias Negri、Ashraf H. Abadi

  DOI：10.1016/j.ejmech.2012.09.029

  日期：2012.11

  By studying the co-crystal information of interactions between PDE5 and its inhibitors, forty new tetrahydro-beta-carbolines based-analogues were synthesized, and tested for their PDE5 inhibition. Some compounds were as active as tadalafil in inhibiting PDE5 and of better selectivity profile particularly versus PDE11A, the nature of the terminal ring and its nitrogen substituent are the main determinants of selectivity. Ensemble docking confirmed the role of H-loop closed conformer in activity versus its occluded and open forms. Conformational studies showed the effect of bulkiness of the terminal ring N-alkyl substituent on the formation of stable enzyme ligands conformers. The difference in potencies of hydantoin and piperazinedione analogues, together with the necessity of C-5/C-6 R-absolute configuration has been revealed through molecular docking. (C) 2012 Elsevier Masson SAS. All rights reserved.