3-[[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl]amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 3-[[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl]amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoic acid
• 化学式: C₃₈H₃₄N₃O₃Pol
• InChiKey: HLIFXCXTXPXGNH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  None
• 重原子数：
  None
• 可旋转键数：
  None
• 环数：
  None
• sp3杂化的碳原子比例：
  None
• 拓扑面积：
  None
• 氢给体数：
  None
• 氢受体数：
  None

反应信息

• 作为反应物：
  描述：

  3-[[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl]amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoic acid 、 FMOC-beta-丙氨酸 在 哌啶 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 Fmoc-Dpr(ivDde)-OH
  参考文献：
  名称：

  Efficient Solid-Phase Synthesis of a Series of Cyclic and Linear Peptoid−Dexamethasone Conjugates for the Cell Permeability Studies

  摘要：

  Cyclic peptides and their cyclic analogs have received a great deal of attention because of their numerous interesting biological activities and their challenging chemical synthesis. It has also been hypothesized that they might improve the cell permeability compared to linear molecules by providing internal hydrogen bonding and generally decreasing the conformational flexibility. In this study, a series of cyclic and linear peptoid dexamethasone conjugates were rationally designed and efficiently synthesized on solid-phase for systematic cell permeability studies using reporter gene-based assays. These model compounds should be used to reveal how the cell permeability of cyclic molecules is affected by several physicochemical properties, especially, the reduced conformational flexibility and the ring size. In addition, the synthetic strategy that was adopted in this study can also provide a robust platform for postchemical modifications of various molecular scaffolds in solid-phase or solution-phase syntheses.

  DOI：

  10.1021/cc9001857
• 作为产物：
  描述：

  Fmoc-Rink resin 、 4'-{3-[(3R)-3-(dimethylamino)pyrrolidinyl]propoxy}[1,1'-biphenyl]-4-carbonitrile 在 哌啶 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 3-[[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl]amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoic acid
  参考文献：
  名称：

  Efficient Solid-Phase Synthesis of a Series of Cyclic and Linear Peptoid−Dexamethasone Conjugates for the Cell Permeability Studies

  摘要：

  Cyclic peptides and their cyclic analogs have received a great deal of attention because of their numerous interesting biological activities and their challenging chemical synthesis. It has also been hypothesized that they might improve the cell permeability compared to linear molecules by providing internal hydrogen bonding and generally decreasing the conformational flexibility. In this study, a series of cyclic and linear peptoid dexamethasone conjugates were rationally designed and efficiently synthesized on solid-phase for systematic cell permeability studies using reporter gene-based assays. These model compounds should be used to reveal how the cell permeability of cyclic molecules is affected by several physicochemical properties, especially, the reduced conformational flexibility and the ring size. In addition, the synthetic strategy that was adopted in this study can also provide a robust platform for postchemical modifications of various molecular scaffolds in solid-phase or solution-phase syntheses.

  DOI：

  10.1021/cc9001857

文献信息

• SPIRO DERIVATIVES AND ADHESION MOLECULE INHIBITORS COMPRISING THE SAME AS THE ACTIVE INGREDIENT
  申请人：TORAY INDUSTRIES, INC.

  公开号：EP1489081A1

  公开（公告）日：2004-12-22

  Disclosed is the use of an adhesion molecule inhibitor that is effective in the prevention and treatment of inflammatory diseases caused by infiltration of leukocytes such as monocytes, lymphocytes and eosinophils, by inhibiting cell infiltration which mediates adhesion molecules, especially adhesion molecule VLA-4. Since the spiro acid derivatives according to the present invention are excellent in the effect of inhibiting cell adhesion via adhesion molecules, especially adhesion molecule VLA-4, they are useful as therapeutic drugs against various inflammatory diseases. For example, provided are the spiro derivative and the adhesion molecule inhibitor which includes as an active ingredient the spiro derivative as shown by the below formula (18).

  本发明公开了一种粘附分子抑制剂，通过抑制介导粘附分子（尤其是粘附分子 VLA-4）的细胞浸润，可有效预防和治疗由单核细胞、淋巴细胞和嗜酸性粒细胞等白细胞浸润引起的炎症性疾病。 由于本发明的螺酸衍生物在抑制细胞通过粘附分子（尤其是粘附分子 VLA-4）的粘附方面具有出色的效果，因此可作为治疗药物用于各种炎症性疾病。例如，本发明提供了螺衍生物和粘附分子抑制剂，其活性成分包括如下式（18）所示的螺衍生物。
• PCSK9 antagonists bicyclo-compounds
  申请人：Merck Sharp & Dohme Corp.

  公开号：US11306125B2

  公开（公告）日：2022-04-19

  Disclosed are compounds of Formula I, or a salt thereof cyclic polypeptide of Formula I: Formula I where A, B, E, R4, and R8 are as defined herein, which compounds have properties for antagonizing PCSK9. Also described are pharmaceutical formulations comprising the compounds of Formula I or their salts, and methods of treating cardiovascular disease and conditions related to PCSK9 activity, e.g. atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular disease and cardiometabolic conditions

  公开了式 I 的化合物或其盐式 I 的环状多肽：式 I 其中 A、B、E、R4 和 R8 如本文所定义，这些化合物具有拮抗 PCSK9 的特性。还描述了包含式 I 化合物或其盐的药物制剂，以及治疗心血管疾病和与 PCSK9 活性有关的病症（如动脉粥样硬化、高胆固醇血症、冠心病、代谢综合征、急性冠状动脉综合征或相关心血管疾病和心脏代谢病症）的方法。
• PCSK9 ANTAGONIST BICYCLO-COMPOUNDS
  申请人：MERCK SHARP & DOHME CORP.

  公开号：EP3810129A1

  公开（公告）日：2021-04-28
• Spiro derivatives and adhesion molecule inhibitors comprising the same as active ingredient
  申请人：Ishigaki Takeshi

  公开号：US20060241132A1

  公开（公告）日：2006-10-26

  Disclosed is the use of an adhesion molecule inhibitor that is effective in the prevention and treatment of inflammatory diseases caused by infiltration of leukocytes such as monocytes, lymphocytes and eosindphils, by inhibiting cell infiltration which mediates adhesion molecules, especially adhesion molecule VLA-4. Since the spiro acid derivatives according to the present invention are excellent in the effect of inhibiting cell adhesion via adhesion molecules, especially adhesion molecule VLA-4, they are useful as therapeutic drugs against various inflammatory diseases. For example, provided are the spiro derivative and the adhesion molecule inhibitor which includes as an active ingredient the spiro derivative as shown by the below formula (18).
• PCSK9 ANTAGONISTS BICYCLO-COMPOUNDS
  申请人：Merck Sharp & Dohme Corp.

  公开号：US20210214395A1

  公开（公告）日：2021-07-15

  Disclosed are compounds of Formula I, or a salt thereof cyclic polypeptide of Formula I: Formula I where A, B, E, R 4 , and R 8 are as defined herein, which compounds have properties for antagonizing PCSK9. Also described are pharmaceutical formulations comprising the compounds of Formula I or their salts, and methods of treating cardiovascular disease and conditions related to PCSK9 activity, e.g. atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular disease and cardiometabolic conditions