methyl (4S,7S,12bR)-7-amino-6-oxo-2,3,4,7,8,12b-hexahydro-1H-pyrido[2,1-a][2]benzazepine-4-carboxylate | 122882-34-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (4S,7S,12bR)-7-amino-6-oxo-2,3,4,7,8,12b-hexahydro-1H-pyrido[2,1-a][2]benzazepine-4-carboxylate
• CAS: 122882-34-2
• 化学式: C₁₆H₂₀N₂O₃
• 分子量: 288.346
• InChiKey: HRGMSUOEOXGYDR-MJBXVCDLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  72.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (4S,7S,12bR)-7-amino-6-oxo-2,3,4,7,8,12b-hexahydro-1H-pyrido[2,1-a][2]benzazepine-4-carboxylate 在 亚硝酸丙酯 、 三氟甲磺酸 、 potassium carbonate 、 溶剂黄146 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 (4S,12bR)-6-Oxo-1,2,3,4,6,12b-hexahydro-benzo[c]pyrido[1,2-a]azepine-4-carboxylic acid methyl ester
  参考文献：
  名称：

  The conversion of a diazolactam to an α-methylenelactam: An entrance to new conformationally restricted inhibitors of angiotensin-converting enzyme

  摘要：

  DOI：

  10.1016/s0040-4039(00)94635-5
• 作为产物：
  描述：

  methyl (4S,7S,12bR)-7-(1,3-dioxoisoindol-2-yl)-6-oxo-2,3,4,7,8,12b-hexahydro-1H-pyrido[2,1-a][2]benzazepine-4-carboxylate 在 一水合肼 作用下， 以 甲醇 为溶剂， 反应 72.0h， 生成 methyl (4S,7S,12bR)-7-amino-6-oxo-2,3,4,7,8,12b-hexahydro-1H-pyrido[2,1-a][2]benzazepine-4-carboxylate
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Tricyclic, Conformationally Constrained Small-Molecule Mimetics of Second Mitochondria-Derived Activator of Caspases

  摘要：

  A series of tricyclic, conformationally constrained Smac mimetics have been designed, synthesized, and evaluated. The most potent compound 6 (WS-5) binds to XIAP, cIAP-1, and cIAP-2 with K-i of 18, 1.1, and 4.2 nM, respectively. Compound 6 antagonizes XIAP in a functional assay, induces cIAP-1 degradation, inhibits cell growth with an IC50 of 68 nM in the MDA-MB-231 cancer cell line, and effectively induces cancer cells to undergo apoptosis.

  DOI：

  10.1021/jm801146d

文献信息

• N -Formyl hydroxylamine containing dipeptides: generation of a new class of vasopeptidase inhibitors
  作者：Jeffrey A. Robl、Ligaya M. Simpkins、Magdi M. Asaad

  DOI：10.1016/s0960-894x(99)00671-x

  日期：2000.2

  Four primary zinc-binding pharmacophores (thiols, carboxylates, phosphorus acids, and hydroxamates) have been utilized in generating inhibitors of zinc metalloproteases such as ACE, NEP, the MMPs, and ECE. Although compounds which inhibit the activity of both ACE and NEP (vasopeptidase inhibitors, VPIs) have been reported which incorporate a thiol, carboxylate, or phosphorus acid pharmacophore, the generation of hydroxamate based vasopeptidase inhibitors has remained elusive. Herein we report the first potent vasopeptidase inhibitors which were generated from the incorporation of conformationally restricted dipeptide mimetics to an N-formyl hydroxylamine zinc-binding group. Compounds such as 13c and 13d are among the most potent in this series, exhibiting in vitro activity comparable to other classes of inhibitors. (C) 2000 Elsevier Science Ltd. All rights reserved.
• The conversion of a diazolactam to an α-methylenelactam: An entrance to new conformationally restricted inhibitors of angiotensin-converting enzyme
  作者：Gary A Flynn、Douglas W Beight、Edward W Huber、Philippe Bey

  DOI：10.1016/s0040-4039(00)94635-5

  日期：1990.1
• Design, Synthesis, and Evaluation of Tricyclic, Conformationally Constrained Small-Molecule Mimetics of Second Mitochondria-Derived Activator of Caspases
  作者：Bin Zhang、Zaneta Nikolovska-Coleska、Yan Zhang、Longchuan Bai、Su Qiu、Chao-Yie Yang、Haiying Sun、Shaomeng Wang、Yikang Wu

  DOI：10.1021/jm801146d

  日期：2008.12.11

  A series of tricyclic, conformationally constrained Smac mimetics have been designed, synthesized, and evaluated. The most potent compound 6 (WS-5) binds to XIAP, cIAP-1, and cIAP-2 with K-i of 18, 1.1, and 4.2 nM, respectively. Compound 6 antagonizes XIAP in a functional assay, induces cIAP-1 degradation, inhibits cell growth with an IC50 of 68 nM in the MDA-MB-231 cancer cell line, and effectively induces cancer cells to undergo apoptosis.