N-ethyl-2-(5-fluoroindol-3-yl)ethan-1-amine | 1223736-89-7

• 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: N-ethyl-2-(5-fluoroindol-3-yl)ethan-1-amine
• 英文别名: Ethyl-[2-(5-fluoro-1H-indol-3-yl)-ethyl]amine；N-ethyl-2-(5-fluoro-1H-indol-3-yl)ethanamine
• CAS: 1223736-89-7
• 化学式: C₁₂H₁₅FN₂
• 分子量: 206.263
• InChiKey: GKPVFLDXGOMXHI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  27.8
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-ethyl-2-(5-fluoroindol-3-yl)ethan-1-amine 、 甲基磺酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 5-fluoro-3-(2-(N-ethylmethanesulfonamido)ethyl)-1H-indole
  参考文献：
  名称：

  Aromatic N-heterocycle derivatives for use as medicine

  摘要：

  该发明涉及化合物，或其药学上可接受的盐、溶剂化合物、水合物、多晶型、共晶体，其中所述化合物具有以下结构式A-B（I），其中A是取代或非取代的芳香N-杂环；B是-[C(R1)(R2)]n-R3，其中n是1到10之间的整数，R1和R2在n个单位中分别独立地表示从氢、取代或非取代的C1-C10烷基、卤素、氧衍生物、硫衍生物、取代或非取代的C3-C10环烷基、取代或非取代的C6-C18芳基、取代或非取代的C2-C10烯基、取代或非取代的C2-C10炔基中选择的取代基，R3表示从氢、取代或非取代的C1-C10烷基、卤素、取代或非取代的C3-C10环烷基、取代或非取代的C6-C18芳基、取代或非取代的C2-C10烯基、取代或非取代的C2-C10炔基、氨基、杂环、硫氰酸酯、硫衍生物、羟胺、酰胺、磺胺、氨基磺酮衍生物、醚、硫醚、酯、硫酯、叠氮、偶氮、氰基、硝基、硝氧基、氨基甲酸酯、硫代氨基甲酸酯、亚硝基、亚唑、羰基、磷酸酯、膦酸酯、氨基甲酰磷酸酯中选择的取代基；但是，当A是5-氟吲哚时，B与5-氟吲哚基团的第3位结合，R1为氢，n在2到10之间，R3不是-NR4R5，其中R4和R5分别独立地表示从氢、C1-C10烷基、C3-C10环烷基、氨基烷基中选择的取代基，或R4和R5与它们连接的氮原子一起形成四到十元杂环，R2不是在n个单位中分别独立地表示从氢、C1-C10烷基、卤素、烷氧基、氨基烷基和烷基氨中选择的取代基；用于治疗或预防神经和/或炎症性疾病或障碍。该发明还提供了用于抑制髓过氧化物酶酶活性或低密度脂蛋白氧化的药物组合物和体外方法。

  公开号：

  EP2682119A1
• 作为产物：
  描述：

  5-fluoro-3-(2-hydroxyethyl)-1H-indole methanesulfonate 、 乙胺 以 1,4-二氧六环 、 水 为溶剂， 反应 4.0h， 以40%的产率得到N-ethyl-2-(5-fluoroindol-3-yl)ethan-1-amine
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Pharmacological Evaluation of 3-(Aminoalkyl)-5-fluoroindoles as Myeloperoxidase Inhibitors

  摘要：

  Oxidized low-density lipoproteins (LDLs) accumulate in the vascular wall and promote local inflammation, which contributes to the progression of the atheromatous plaque. The key role of myeloperoxidase (MPO) in this process is related to its ability to modify APO B-100 in the intima and at the surface of endothelial cells. A series of 3-(aminoalkyl)-5-fluoroindole analogues was designed and synthesized by exploiting the structure-based docking of 5-fluorotryptamine, a known MPO inhibitor. In vitro assays were used to study the effects of these compounds on the inhibition of MPO-mediated taurine chlorination and oxidation of LDLs. The kinetics of the interaction between the MPO redox intermediates, Compounds I and II, and these inhibitors was also investigated. The most potent molecules possessed a 4- or 5-carbon aminoalkyl side chain and no substituent on the amino group. The mode of binding of these analogues and the mechanism of inhibition is discussed with respect to the structure of MPO and its halogenation and peroxidase cycles.

  DOI：

  10.1021/jm1009988

文献信息

• PHENETHYLAMIDE DERIVATIVES AND THEIR HETEROCYCLIC ANALOGUES
  申请人：Aissaoui Hamed

  公开号：US20110212968A1

  公开（公告）日：2011-09-01

  The invention relates to novel phenethylamide derivatives and their wherein A, B, R 1 , R 2 and R 3 are as described in the application, and to the use of such compounds, or of pharmaceutically acceptable salts of such compounds, as medicaments, especially as orexin receptor antagonists.

  本发明涉及新型苯乙酰胺衍生物及其其中A、B、R1、R2和R3如本申请中所述的衍生物的药物学上可接受的盐的使用，特别是作为药物，尤其是作为促进睡眠的药物，如促进睡眠的药物。
• Aromatic N-heterocycle derivatives for use as medicine
  申请人：Université Libre de Bruxelles

  公开号：EP2682119A1

  公开（公告）日：2014-01-08

  The invention relates to compounds, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal thereof, wherein said compound is of formula A-B (I) wherein A is substitued or not aromatic N-heterocycle; and B is -[C(R1)(R2)]n-R3 wherein n is an integer between 1 and 10, R1 and R2 represent independently in each of the n units a substituent selected from the group consisting of hydrogen, substituted or not C1-C10 alkyl, halogen, oxy derivatives, thioderivatives, substituted or not C3-C10 cycloalkyl, substituted or not C6-C18 aryl, substituted or not C2-C10 alkenyl, substituted or not C2-C10 alkynyl, R3 represents a substituent selected from the group consisting of hydrogen, substituted or not C1-C10 alkyl, halogen, substituted or not C3-C10 cycloalkyl, substituted or not C6-C18 aryl, substituted or not C2-C10 alkenyl, substituted or not C2-C10 alkynyl, amino, heterocycle, thiocyanate, thio derivatives, hydroxylamine, amido, sulfonamide, amino sulfone derivatives, ether, thioether, ester, thioester, azido, azo, cyano, nitro, nitrooxy, carbamate, thiocarbamate, sulfinyl derivative, sulfonyl derivatives, acyl derivatives, oxy derivatives, ureido, thioureido, imino, oximino, hydrazino, thioamido, carboxylic, phosphate, phosphonate, carbamoyl phosphate; with the proviso that when A is 5-fluoroindole, B is bonded at position 3 of the 5-fluoroindole moiety, R1 is hydrogen and n is between 2 and 10, R3 is not -NR4R5 wherein R4 and R5 independently represent a substituent selected from the group consisting of hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, aminoalkyl, or R4 and R5 taken together with the nitrogen atom to which they are attached to form a four to ten-membered heterocycle, and R2 is not independently in each of the n units a substituent selected from the group consisting of hydrogen, C1-C10 alkyl, halogen, alkoxy, aminoalkyl, and alkylamino; for the treatment or the prophylaxis of neurologic and/or inflammatory diseases or disorders. The present invention also provides pharmaceutical composition and in vitro method for inhibiting myeloperoxidase enzyme activity or low density lipoproteins oxidation.

  该发明涉及化合物，或其药学上可接受的盐、溶剂化合物、水合物、多晶型、共晶体，其中所述化合物具有以下结构式A-B（I），其中A是取代或非取代的芳香N-杂环；B是-[C(R1)(R2)]n-R3，其中n是1到10之间的整数，R1和R2在n个单位中分别独立地表示从氢、取代或非取代的C1-C10烷基、卤素、氧衍生物、硫衍生物、取代或非取代的C3-C10环烷基、取代或非取代的C6-C18芳基、取代或非取代的C2-C10烯基、取代或非取代的C2-C10炔基中选择的取代基，R3表示从氢、取代或非取代的C1-C10烷基、卤素、取代或非取代的C3-C10环烷基、取代或非取代的C6-C18芳基、取代或非取代的C2-C10烯基、取代或非取代的C2-C10炔基、氨基、杂环、硫氰酸酯、硫衍生物、羟胺、酰胺、磺胺、氨基磺酮衍生物、醚、硫醚、酯、硫酯、叠氮、偶氮、氰基、硝基、硝氧基、氨基甲酸酯、硫代氨基甲酸酯、亚硝基、亚唑、羰基、磷酸酯、膦酸酯、氨基甲酰磷酸酯中选择的取代基；但是，当A是5-氟吲哚时，B与5-氟吲哚基团的第3位结合，R1为氢，n在2到10之间，R3不是-NR4R5，其中R4和R5分别独立地表示从氢、C1-C10烷基、C3-C10环烷基、氨基烷基中选择的取代基，或R4和R5与它们连接的氮原子一起形成四到十元杂环，R2不是在n个单位中分别独立地表示从氢、C1-C10烷基、卤素、烷氧基、氨基烷基和烷基氨中选择的取代基；用于治疗或预防神经和/或炎症性疾病或障碍。该发明还提供了用于抑制髓过氧化物酶酶活性或低密度脂蛋白氧化的药物组合物和体外方法。
• Structure-Based Design, Synthesis, and Pharmacological Evaluation of 3-(Aminoalkyl)-5-fluoroindoles as Myeloperoxidase Inhibitors
  作者：Jalal Soubhye、Martine Prévost、Pierre Van Antwerpen、Karim Zouaoui Boudjeltia、Alexandre Rousseau、Paul G. Furtmüller、Christian Obinger、Michel Vanhaeverbeek、Jean Ducobu、Jean Nève、Michel Gelbcke、Franc¸ois Dufrasne

  DOI：10.1021/jm1009988

  日期：2010.12.23

  Oxidized low-density lipoproteins (LDLs) accumulate in the vascular wall and promote local inflammation, which contributes to the progression of the atheromatous plaque. The key role of myeloperoxidase (MPO) in this process is related to its ability to modify APO B-100 in the intima and at the surface of endothelial cells. A series of 3-(aminoalkyl)-5-fluoroindole analogues was designed and synthesized by exploiting the structure-based docking of 5-fluorotryptamine, a known MPO inhibitor. In vitro assays were used to study the effects of these compounds on the inhibition of MPO-mediated taurine chlorination and oxidation of LDLs. The kinetics of the interaction between the MPO redox intermediates, Compounds I and II, and these inhibitors was also investigated. The most potent molecules possessed a 4- or 5-carbon aminoalkyl side chain and no substituent on the amino group. The mode of binding of these analogues and the mechanism of inhibition is discussed with respect to the structure of MPO and its halogenation and peroxidase cycles.