Tetracyclic aza-amide, 12a

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: Tetracyclic aza-amide, 12a
• 英文别名: 17-(3-bromophenyl)sulfonyl-4,6-dimethoxy-11,17-diazatetracyclo[11.3.1.02,11.03,8]heptadeca-3(8),4,6-trien-12-one
• 化学式: C₂₃H₂₅BrN₂O₅S
• 分子量: 521.432
• InChiKey: YMBYLURKHCJQCQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  84.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  cis-2,6-piperidinedicarboxylic acid 在 N-甲基吗啉 、 sodium hydroxide 、 乙酸酐 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 18.0h， 生成 Tetracyclic aza-amide, 12a
  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

• 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.