1-(2,3-二氢-1-苯并呋喃-5-基)哌嗪 | 163521-16-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 1-(2,3-二氢-1-苯并呋喃-5-基)哌嗪
• 英文名称: 1-(2,3-dihydrobenzofuran-5-yl)piperazine
• 英文别名: 5-piperazinyl-2,3-dihydrobenzo[b]furan；4-(2,3-dihydrobenzofuran-5-yl)-piperazine；1-(2,3-Dihydro-1-benzofuran-5-yl)piperazine
• CAS: 163521-16-2
• 化学式: C₁₂H₁₆N₂O
• 分子量: 204.272
• InChiKey: DVVCESKEEKGQDK-UHFFFAOYSA-N

物化性质

• 熔点：
  213-215 °C(Solv: ethanol (64-17-5))
• 沸点：
  392.1±42.0 °C(Predicted)
• 密度：
  1.148±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  24.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2,3-二氢-1-苯并呋喃-5-基)哌嗪 在 三甲基乙酰氯 、 红铝 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 50.0h， 生成 3-{4-[4-(2,3-Dihydro-benzofuran-5-yl)-piperazin-1-yl]-butyl}-5-methoxy-1H-indole
  参考文献：
  名称：

  Indolebutylamines as Selective 5-HT_1A Agonists

  摘要：

  A series of new 1-[4-(indol-3-yl)butyl]-4-arylpiperazines was prepared to identify highly selective and potent 5-HT1A agonists as potential pharmacological tools in studies of mood disorders. The combination of structural elements (indole-alkyl-amine and aryl-piperazine) known to introduce 5-HT1A receptor affinity and the proper selection of substituents (R on the indole moiety and R' on the aryl moiety) led to compounds with high receptor specificity and affinity. In particular, the introduction of the methyl ether or the unsubstituted carboxamide as substituents in position 5 of the indole (R) guaranteed serotonergic 5-HT1A affinity compared to the unsubstituted analogue. Para-substituted arylpiperazines (R') decreased dopaminergic D-2 binding and increased selectivity for the 5-HT1A receptor. Agonistic 5-HT1A receptor activity was confirmed in vivo in the ultrasonic vocalization test, and the results suggest that the introduction of the carboxamide residue leads to better bioavailability than the corresponding methyl ether. 3-{4-[4-(4-Carbamoylphenyl)piperazin-1-yl}butyl}-1H-indole-5-carboxamide 54 was identified as a highly selective 5-HT1A receptor agonist [GTPgammaS, ED50 = 4.7 nM] with nanomolar 5-HT1A affinity [IC50 = 0.9 nM] and selectivity [D-2, IC50 > 850 nM]. 3-{4-[4-(4-Methoxyphenyl)piperazin-1-yl]butyl}-1H-indole-5-carboxamide 45 is one of the most potent and selective 5-HT1A agonists known [5-HT1A, IC50 = 0.09 nM; D-2, IC50 = 140 nM].

  DOI：

  10.1021/jm040792y
• 作为产物：
  描述：

  二(2-氯乙基)胺盐酸盐 、 5-氨基-2,3-二氢苯并[b]呋喃 在 potassium carbonate 作用下， 以 正丁醇 为溶剂， 反应 24.0h， 以31%的产率得到1-(2,3-二氢-1-苯并呋喃-5-基)哌嗪
  参考文献：
  名称：

  Indolebutylamines as Selective 5-HT_1A Agonists

  摘要：

  A series of new 1-[4-(indol-3-yl)butyl]-4-arylpiperazines was prepared to identify highly selective and potent 5-HT1A agonists as potential pharmacological tools in studies of mood disorders. The combination of structural elements (indole-alkyl-amine and aryl-piperazine) known to introduce 5-HT1A receptor affinity and the proper selection of substituents (R on the indole moiety and R' on the aryl moiety) led to compounds with high receptor specificity and affinity. In particular, the introduction of the methyl ether or the unsubstituted carboxamide as substituents in position 5 of the indole (R) guaranteed serotonergic 5-HT1A affinity compared to the unsubstituted analogue. Para-substituted arylpiperazines (R') decreased dopaminergic D-2 binding and increased selectivity for the 5-HT1A receptor. Agonistic 5-HT1A receptor activity was confirmed in vivo in the ultrasonic vocalization test, and the results suggest that the introduction of the carboxamide residue leads to better bioavailability than the corresponding methyl ether. 3-{4-[4-(4-Carbamoylphenyl)piperazin-1-yl}butyl}-1H-indole-5-carboxamide 54 was identified as a highly selective 5-HT1A receptor agonist [GTPgammaS, ED50 = 4.7 nM] with nanomolar 5-HT1A affinity [IC50 = 0.9 nM] and selectivity [D-2, IC50 > 850 nM]. 3-{4-[4-(4-Methoxyphenyl)piperazin-1-yl]butyl}-1H-indole-5-carboxamide 45 is one of the most potent and selective 5-HT1A agonists known [5-HT1A, IC50 = 0.09 nM; D-2, IC50 = 140 nM].

  DOI：

  10.1021/jm040792y

文献信息

• Synthesis and Structure−Activity Relationship in a Class of Indolebutylpiperazines as Dual 5-HT_1A Receptor Agonists and Serotonin Reuptake Inhibitors
  作者：Timo Heinrich、Henning Böttcher、Rolf Gericke、Gerd D. Bartoszyk、Soheila Anzali、Christoph A. Seyfried、Hartmut E. Greiner、Christoph van Amsterdam

  DOI：10.1021/jm040793q

  日期：2004.9.1

  Systematic structural modifications of indolealkylphenylpiperazines led to improved selectivity and affinity within this class of 5-HT(1A) receptor agonists. Introduction of electron-withdrawing groups in position 5 on the indole raises serotonin transporter affinity, and the cyano group proved to be the best substituent here. 5-Fluoro and 5-cyano substituted indoles show comparable results in in vitro

  吲哚烷基苯基哌嗪的系统结构修饰导致此类5-HT（1A）受体激动剂的选择性和亲和力提高。在吲哚的5位引入吸电子基团提高了5-羟色胺转运蛋白的亲和力，并且氰基被证明是此处最好的取代基。5-氟和5-氰基取代的吲哚在体外和体内试验中显示出可比的结果，并且通过计算分子静电势和偶极矩来支持这些取代基之间的生物等排。在离体（对氯苯丙胺测定）和体内（超声发声）测试中进一步检查了显示出有希望的体外数据的化合物。芳基哌嗪部分的优化表明，5-苯并呋喃基-2-羧酰胺最适合增加5-HT转运蛋白和5-HT（1A）受体的亲和力并抑制D（2）受体的结合。5- [4- [4-（5-氰基-3-吲哚基）丁基] -1-哌嗪基]苯并呋喃-2-羧酰胺29（维拉唑酮，EMD 68843）被确定为高选择性5-HT（1A）受体激动剂[GTPgammaS，ED（50）= 1.1 nM]，具有亚纳摩尔的5-HT（1A）亲和力[IC（50）= 0
• Piperazine, piperidine and 1,2,5,6-tetrahydropyridine
  申请人：Adir et Compagnie

  公开号：US05684020A1

  公开（公告）日：1997-11-04

  A compound selected from those of formula: ##STR1## wherein: A-B, n, D and E are as defined in the specification, their racemic mixtures, and their optical isomers, and also the physiologically tolerable salts thereof with appropriate acids. The products of the invention may be used therapeutically.

  从以下式中选择的化合物：##STR1## 其中：A-B，n，D和E如规范中定义，它们的外消旋混合物，以及它们的光学异构体，以及与适当酸的生理耐受盐。本发明的产品可用于治疗。
• Nouveaux composés de la pipérazine, de la pipéridine et de la 1,2,5,6-tétra-hydropyridine, leur procédé de préparation et les compositions pharmaceutiques les contenant
  申请人：ADIR ET COMPAGNIE

  公开号：EP0745598A1

  公开（公告）日：1996-12-04

  Les composés de formule I: dans laquelle A-Breprésente: CH2-CH, CH=C ou CH2-N, nreprésente zéro ou un nombre entier de 1 à 6 inclus, Dreprésente l'un des systèmes bicycliques suivants: dans lesquels: R1 et R2, identiques ou différents, représentent chacun un atome d'hydrogène ou d'halogène, un radical alkyle ou alkoxy en chaîne droite ou ramifiée ayant de 1 à 5 atomes de carbone inclus ou un radical hydroxy; et E représente un des hétérocycles suivants: leurs formes de mélange racémique ou racémate et d'isomères optiques ou énantiomères, ainsi que leurs sels avec des acides pharmaceutiquement acceptables. Les produits de l'invention peuvent être utilisés en thérapeutique.

  式 I 的化合物 其中 A-B代表：CH2-CH、CH=C 或 -N、 n 代表零或 1 至 6（含 6）的整数、 D 代表下列双环体系之一： 其中 R1 和 R2（可以相同或不同）分别代表氢原子或卤素原子、具有 1 至 5 个碳原子 （含 5 个）的直链或支链烷基或烷氧基或羟基；以及 E 代表下列杂环之一： 它们的外消旋体或外消旋体混合物以及光学异构体或对映体形式、 及其与药学上可接受的酸的盐类。 本发明的产品可用于治疗。
• 6-(4-Benzylpiperazin-1-yl)benzodioxanes as selective ligands at cloned primate dopamine D4 receptors
  作者：Kevin J Hodgetts、Andrzej Kieltyka、Robbin Brodbeck、Jennifer N Tran、Jan W.F Wasley、Andrew Thurkauf

  DOI：10.1016/s0968-0896(01)00226-7

  日期：2001.12

  A series of novel 6-(4-benzylpiperazin-1-yl)benzodioxanes were prepared and screened at selected dopamine receptor subtypes. 6-(4-[4-Chlorobenzyl]piperazin-1-yl)benzodioxane (2d) had high affinity and selectivity for the D-4 dopamine receptor subtype and was identified as a D-4 antagonist via its attenuation of dopamine-induced GT gamma S-35 binding at the D-4 receptor. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Piperidine und Piperazine, die Wirkungen auf das z.n.s. Zeigen
  申请人：MERCK PATENT GmbH

  公开号：EP0648767B1

  公开（公告）日：1997-05-28