3-[2-(2-Methoxyphenyl)-ethyl]-2,4-dioxo-3,9-diaza-bicyclo[3.3.1]nonane-9-carboxylic Acid Benzyl Ester | 255910-82-8

• 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: 3-[2-(2-Methoxyphenyl)-ethyl]-2,4-dioxo-3,9-diaza-bicyclo[3.3.1]nonane-9-carboxylic Acid Benzyl Ester
• 英文别名: benzyl 3-[2-(2-methoxyphenyl)ethyl]-2,4-dioxo-3,9-diazabicyclo[3.3.1]nonane-9-carboxylate
• CAS: 255910-82-8
• 化学式: C₂₄H₂₆N₂O₅
• 分子量: 422.481
• InChiKey: OYQZYQWBHTWIAQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  76.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-[2-(2-Methoxyphenyl)-ethyl]-2,4-dioxo-3,9-diaza-bicyclo[3.3.1]nonane-9-carboxylic Acid Benzyl Ester 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 1-{7-Methoxy-12-oxo-11,17-diazatetracyclo[11.3.1.0^{2,11}.0^{3,8}]heptadeca-3(8),4,6-trien-17-yl}-2-(3,4,5-trimethoxyphenyl)ethane-1,2-dione
  参考文献：
  名称：

  Design, Synthesis, and Biological Activity of Novel Polycyclic Aza-Amide FKBP12 Ligands

  摘要：

  Since the discovery that FK-506 promotes neurite outgrowth, considerable attention has been focused on the development of potent nonimmunosuppressive ligands for FK-506 binding proteins (FKBPs). Such neuroimmunophilin agents have been reported to show neuroregenerative activity in a variety of cell and animal models including neurite outgrowth, age-related cognitive decline, Parkinson's disease, peripheral nerve injury, optic nerve degeneration, and diabetic neuropathy. We have designed and synthesized a unique series of tetracyclic aza-amides that have been shown to be potent FKBP12 rotamase inhibitors. The structure-activity relationships established in this study have demonstrated diverse structural modifications that result in potent rotamase inhibitory activity.

  DOI：

  10.1021/jm049161u
• 作为产物：
  描述：

  cis-2,6-piperidinedicarboxylic acid 在 sodium hydroxide 、 乙酸酐 作用下， 以 甲苯 为溶剂， 反应 18.0h， 生成 3-[2-(2-Methoxyphenyl)-ethyl]-2,4-dioxo-3,9-diaza-bicyclo[3.3.1]nonane-9-carboxylic Acid Benzyl Ester
  参考文献：
  名称：

  Design, Synthesis, and Biological Activity of Novel Polycyclic Aza-Amide FKBP12 Ligands

  摘要：

  Since the discovery that FK-506 promotes neurite outgrowth, considerable attention has been focused on the development of potent nonimmunosuppressive ligands for FK-506 binding proteins (FKBPs). Such neuroimmunophilin agents have been reported to show neuroregenerative activity in a variety of cell and animal models including neurite outgrowth, age-related cognitive decline, Parkinson's disease, peripheral nerve injury, optic nerve degeneration, and diabetic neuropathy. We have designed and synthesized a unique series of tetracyclic aza-amides that have been shown to be potent FKBP12 rotamase inhibitors. The structure-activity relationships established in this study have demonstrated diverse structural modifications that result in potent rotamase inhibitory activity.

  DOI：

  10.1021/jm049161u

文献信息

• Compounds, pharmaceutical compositions, and methods for stimulating neuronal growth and elongation
  申请人：Pfizer Inc

  公开号：US06630472B1

  公开（公告）日：2003-10-07

  Compounds that inhibit the peptidyl-prolyl isomerase (rotamase) enzyme activity of the FK-506 binding protein (FKBP) and compositions comprising these compounds are described. The FKBP-inhibiting compounds have a bicyclic [3.3.1], [4.3.1] or polycyclic azaamide nucleus. Pharmaceutical compositions containing such compounds help stimulate the outgrowth of neurites in nerve cells and augmenting nerve regeneration. Methods of treating nerve cells with such compositions are useful to promote repair of neuronal damage caused by disease and physical trauma.

  本文描述了抑制FK-506结合蛋白（FKBP）的肽酰基-脯氨酰异构酶（旋转酶）酶活性的化合物以及包含这些化合物的组合物。这些抑制FKBP的化合物具有双环[3.3.1]、[4.3.1]或多环氮杂酰胺核。含有这样化合物的制药组合物有助于刺激神经细胞的轴突生长，增强神经再生。使用这样的组合物治疗神经细胞的方法有助于促进由疾病和身体创伤引起的神经元损伤的修复。
• [EN] COMPOUNDS, COMPOSITIONS, AND METHODS FOR STIMULATING NEURONAL GROWTH AND ELONGATION<br/>[FR] COMPOSES, COMPOSITIONS ET PROCEDES DE STIMULATION DE LA CROISSANCE ET DE L'ALLONGEMENT NEURONAUX
  申请人：AGOURON PHARMA

  公开号：WO2000004020A1

  公开（公告）日：2000-01-27

  Compounds that inhibit the peptidyl-prolyl isomerase (rotamase) enzyme activity of the FK-506 binding protein (FKBP) and compositions comprising these compounds are described. The FKBP-inhibiting compounds have a bicyclic [3.3.1], [4.3.1] or polycyclic azaamide nucleus. Pharmaceutical compositions containing such compounds help stimulate the outgrowth of neurites in nerve cells and augmenting nerve regeneration. Methods of treating nerve cells with such compositions are useful to promote repair of neuronal damage caused by disease and physical trauma.

  本文描述了能抑制FK-506结合蛋白(FKBP)的肽酰脯氨酸异构酶(rotamase)酶活性的化合物，以及包含这些化合物的组合物。这些FKBP抑制化合物具有双环[3.3.1]、[4.3.1]或多环氮杂甲酰胺核。含有这些化合物的制药组合物有助于刺激神经细胞的突起生长和增强神经再生。使用这些组合物治疗神经细胞的方法有助于促进由疾病和物理创伤引起的神经损伤的修复。
• COMPOUNDS, COMPOSITIONS, AND METHODS FOR STIMULATING NEURONAL GROWTH AND ELONGATION
  申请人：AGOURON PHARMACEUTICALS, INC.

  公开号：EP1098897A1

  公开（公告）日：2001-05-16
• US6630472B1
  申请人：——

  公开号：US6630472B1

  公开（公告）日：2003-10-07
• Design, Synthesis, and Biological Activity of Novel Polycyclic Aza-Amide FKBP12 Ligands
  作者：Raymond A. Hudack,、Nancy S. Barta、Chuangxing Guo、Judith Deal、Liming Dong、Lorraine K. Fay、Bradley Caprathe、Arindam Chatterjee、Darin Vanderpool、Christopher Bigge、Richard Showalter、Steve Bender、Corinne E. Augelli-Szafran、Elizabeth Lunney、Xinjun Hou

  DOI：10.1021/jm049161u

  日期：2006.2.1

  Since the discovery that FK-506 promotes neurite outgrowth, considerable attention has been focused on the development of potent nonimmunosuppressive ligands for FK-506 binding proteins (FKBPs). Such neuroimmunophilin agents have been reported to show neuroregenerative activity in a variety of cell and animal models including neurite outgrowth, age-related cognitive decline, Parkinson's disease, peripheral nerve injury, optic nerve degeneration, and diabetic neuropathy. We have designed and synthesized a unique series of tetracyclic aza-amides that have been shown to be potent FKBP12 rotamase inhibitors. The structure-activity relationships established in this study have demonstrated diverse structural modifications that result in potent rotamase inhibitory activity.