methyl 2-(6-chloro-9-methyl-9H-carbazol-2-yl)propanoate | 1402840-47-4

• 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: methyl 2-(6-chloro-9-methyl-9H-carbazol-2-yl)propanoate
• 英文别名: Methyl 2-(6-chloro-9-methylcarbazol-2-yl)propanoate；methyl 2-(6-chloro-9-methylcarbazol-2-yl)propanoate
• CAS: 1402840-47-4
• 化学式: C₁₇H₁₆ClNO₂
• 分子量: 301.773
• InChiKey: XVYAPEQXAIFNTJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  31.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  methyl 2-(6-chloro-9-methyl-9H-carbazol-2-yl)propanoate 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 12.0h， 以85%的产率得到2-(6-chloro-9-methyl-9H-carbazol-2-yl)propanoic acid
  参考文献：
  名称：

  Identification and Characterization of Carprofen as a Multitarget Fatty Acid Amide Hydrolase/Cyclooxygenase Inhibitor

  摘要：

  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.

  DOI：

  10.1021/jm3011146
• 作为产物：
  描述：

  卡洛芬 在 硫酸 、 caesium carbonate 作用下， 以 乙腈 为溶剂， 反应 24.0h， 生成 methyl 2-(6-chloro-9-methyl-9H-carbazol-2-yl)propanoate
  参考文献：
  名称：

  Identification and Characterization of Carprofen as a Multitarget Fatty Acid Amide Hydrolase/Cyclooxygenase Inhibitor

  摘要：

  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.

  DOI：

  10.1021/jm3011146

文献信息

• Repurposing anti-inflammatory drugs for fighting planktonic and biofilm growth. New carbazole derivatives based on the NSAID carprofen: synthesis, in silico and in vitro bioevaluation
  作者：Florea Dumitrascu、Mino R. Caira、Speranta Avram、Catalin Buiu、Ana Maria Udrea、Ilinca Margareta Vlad、Irina Zarafu、Petre Ioniță、Diana Camelia Nuță、Marcela Popa、Mariana-Carmen Chifiriuc、Carmen Limban

  DOI：10.3389/fcimb.2023.1181516

  日期：——

  compound was 1i, bearing one chlorine and two bromine atoms, as well as the CO2Me group. Among the tested derivatives, 1h bearing one chlorine and two bromine atoms has exhibited the widest antibacterial spectrum and the most intensive inhibitory activity, especially against the Gram-positive strains, in planktonic and biofilm growth state. The compounds 1a (bearing one chlorine, one NO2 and one CO2Me group)

  简介快速发现替代抗菌药物的一个有希望的线索是重新利用其他药物，例如用于对抗细菌感染和抗菌药物耐药性的非甾体抗炎药（NSAID）。方法一系列基于现成抗微生物药物的新型咔唑衍生物消炎药卡洛芬是由卡洛芬及其酯经硝化、卤化、N-烷基化而得。这些咔唑化合物的结构通过NMR和IR光谱确定。根据 1H NMR 谱图确定了咔唑环上通过硝化和卤化发生的区域选择性亲电取代。还测定了通过卡洛芬二溴化获得的两种代表性衍生物的单晶X射线结构。使用DPPH法测定总抗氧化能力(TAC)。使用定量方法进行抗菌活性测定，从而确定革兰氏阳性菌（金黄色葡萄球菌、粪肠球菌）和革兰氏阴性菌（大肠杆菌、铜绿假单胞菌）的最小抑制/杀菌/生物膜根除浓度（MIC/MBC/MBEC） ）菌株。已进行计算分析来评估药物和先导物相似性、药代动力学 (ADME-Tox) 和药物基因组学概况。结果和讨论 3,8-二溴卡洛芬及其甲酯的晶体 X 射线结