benzyl 2-(3-chloro-9H-carbazol-7-yl)propionate | 166408-09-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: benzyl 2-(3-chloro-9H-carbazol-7-yl)propionate
• 英文别名: benzyl 2-(6-chloro-9H-carbazol-2-yl)propanoate
• CAS: 166408-09-9
• 化学式: C₂₂H₁₈ClNO₂
• 分子量: 363.843
• InChiKey: AFVSEMWRURACDS-UHFFFAOYSA-N

物化性质

• 沸点：
  544.7±40.0 °C(Predicted)
• 密度：
  1.305±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  42.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  benzyl 2-(3-chloro-9H-carbazol-7-yl)propionate 在 盐酸 、 sodium hydride 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 12.0h， 生成 BSc4051
  参考文献：
  名称：

  NSAID-derived γ-secretase modulation requires an acidic moiety on the carbazole scaffold

  摘要：

  Modulation of gamma-secretase activity holds potential for the treatment of Alzheimer's disease. Most NSAID-derived gamma-secretase modulators feature a carboxylic acid, which may impair blood-brain barrier permeation. The structure activity relationship of 33 carbazoles featuring diverse carboxylic acid isosteres or metabolic precursors thereof was established in a cellular amyloid secretion assay. The modulatory activity was observed for acidic moieties and metabolically labile esters only, which supports our hypothesis of an acid-lysine interaction to be relevant for this type of gamma-secretase modulators. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.06.062
• 作为产物：
  描述：

  溴甲苯 、 卡洛芬 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 以98%的产率得到benzyl 2-(3-chloro-9H-carbazol-7-yl)propionate
  参考文献：
  名称：

  Scaffold of the Cyclooxygenase-2 (COX-2) Inhibitor Carprofen Provides Alzheimer γ-Secretase Modulators

  摘要：

  N-Sulfonylated and N-alkylated carprofen derivatives were investigated for their inhibition and modulation of gamma-secretase, which is associated with Alzheimer's disease. The introduction of a lipophilic substituent transformed the COX-2 inhibitor carprofen into a potent gamma-secretase modulator. Several compounds (e.g., 9p, 11f) caused selective reduction of A beta(42) and an increase of A beta(38). The most active compounds displayed activities in the low micromolar range and no effect on the gamma-secretase cleavage at the epsilon-site.

  DOI：

  10.1021/jm0610200

文献信息

• Identification and Characterization of Carprofen as a Multitarget Fatty Acid Amide Hydrolase/Cyclooxygenase Inhibitor
  作者：Angelo D. Favia、Damien Habrant、Rita Scarpelli、Marco Migliore、Clara Albani、Sine Mandrup Bertozzi、Mauro Dionisi、Glauco Tarozzo、Daniele Piomelli、Andrea Cavalli、Marco De Vivo

  DOI：10.1021/jm3011146

  日期：2012.10.25

  Pain and inflammation are major therapeutic areas for drug discovery. Current drugs for these pathologies have limited efficacy, however, and often cause a number of unwanted side effects. In the present study, we identify the nonsteroidal anti-inflammatory drug carprofen as a multitarget-directed ligand that simultaneously inhibits cyclooxygenase-1 (COX-1), COX-2, and fatty acid amide hydrolase (FAAH). Additionally, we synthesized and tested several derivatives of carprofen, sharing this multitarget activity. This may result in improved analgesic efficacy and reduced side effects (Naidu et al. J. Pharmacol. Exp. Ther. 2009, 329, 48-56; Fowler, C. J.; et al. J. Enzyme Inhib. Med. Chem. 2012, in press; Sasso et al. Pharmacol. Res. 2012, 65, 553). The new compounds are among the most potent multitarget FAAH/COX inhibitors reported so far in the literature and thus may represent promising starting points for the discovery of new analgesic and anti-inflammatory drugs.
• NSAID-derived γ-secretase modulation requires an acidic moiety on the carbazole scaffold
  作者：Andrea Zall、Daniel Kieser、Nicole Höttecke、Eva C. Naumann、Binia Thomaszewski、Katrin Schneider、Dirk T. Steinbacher、Robert Schubenel、Stefan Masur、Karlheinz Baumann、Boris Schmidt

  DOI：10.1016/j.bmc.2011.06.062

  日期：2011.8

  Modulation of gamma-secretase activity holds potential for the treatment of Alzheimer's disease. Most NSAID-derived gamma-secretase modulators feature a carboxylic acid, which may impair blood-brain barrier permeation. The structure activity relationship of 33 carbazoles featuring diverse carboxylic acid isosteres or metabolic precursors thereof was established in a cellular amyloid secretion assay. The modulatory activity was observed for acidic moieties and metabolically labile esters only, which supports our hypothesis of an acid-lysine interaction to be relevant for this type of gamma-secretase modulators. (C) 2011 Elsevier Ltd. All rights reserved.
• Scaffold of the Cyclooxygenase-2 (COX-2) Inhibitor Carprofen Provides Alzheimer γ-Secretase Modulators
  作者：Rajeshwar Narlawar、Blanca I. Pérez Revuelta、Christian Haass、Harald Steiner、Boris Schmidt、Karlheinz Baumann

  DOI：10.1021/jm0610200

  日期：2006.12.1

  N-Sulfonylated and N-alkylated carprofen derivatives were investigated for their inhibition and modulation of gamma-secretase, which is associated with Alzheimer's disease. The introduction of a lipophilic substituent transformed the COX-2 inhibitor carprofen into a potent gamma-secretase modulator. Several compounds (e.g., 9p, 11f) caused selective reduction of A beta(42) and an increase of A beta(38). The most active compounds displayed activities in the low micromolar range and no effect on the gamma-secretase cleavage at the epsilon-site.