1-chroman-6-yl-piperazine | 163521-17-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-chroman-6-yl-piperazine
• 英文别名: 6-piperazinylchromane；1-(chroman-6-yl)piperazine；1-(3,4-dihydro-2H-1-benzopyran-6-yl)Piperazine；1-(3,4-dihydro-2H-chromen-6-yl)piperazine
• CAS: 163521-17-3
• 化学式: C₁₃H₁₈N₂O
• 分子量: 218.299
• InChiKey: WVLFSMOGFARRCQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 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-chroman-6-yl-piperazine 在 sodium hydroxide 、 potassium carbonate 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 22.0h， 生成 3-[4-(4-chroman-6-yl-piperazin-1-yl)butyl]-1H-indole-5-carboxylic acid
  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：

  3,4-二2H-1-苯并吡喃-6-胺 在 potassium carbonate 作用下， 以 氯苯 为溶剂， 生成 1-chroman-6-yl-piperazine
  参考文献：
  名称：

  6-(4-arylalkylpiperazin-1-yl) benzodioxane and 6-(4-arylalkylpiperazin-1-yl) chromane derivatives: dopamine receptor subtype specific ligands

  摘要：

  本发明涉及下列式的化合物：或其药学上可接受的酸加成盐，其中：R1、R2、R3、R4和R5相同或不同，分别表示氢、卤素、C1-C6烷基、C1-C6烷氧基、C1-C4烷硫基、羟基、氨基、单-或双(C1-C6)烷基氨基、氰基、硝基、三氟甲基或三氟甲氧基；以及X表示氧、键、C1-C2烷基或甲氧基亚甲基。这些化合物对于治疗和/或预防神经心理障碍包括但不限于精神分裂症、躁狂症、痴呆、抑郁症、焦虑、强迫行为、物质滥用、帕金森样运动障碍以及与神经阻滞剂使用相关的运动障碍具有用处。

  公开号：

  US06177566B1
• 作为试剂：
  描述：

  3,4-二2H-1-苯并吡喃-6-胺 、 二(2-氯乙基)胺盐酸盐 、 potassium carbonate 在 sodium hydroxide 、 二氯甲烷 、 Mg2SO4 、 methanol-dichloromethane 、 1-chroman-6-yl-piperazine 作用下， 以 氯苯 为溶剂， 反应 24.0h， 生成 1-chroman-6-yl-piperazine
  参考文献：
  名称：

  6-(4-arylalkylpiperazin-1-yl) benzodioxane and 6-(arylalkylpiperazin-1-yl) chromane derivatives: dopamine receptor subtype specific ligands

  摘要：

  本发明公开了下列化合物：或其在药学上可接受的酸加盐形式，其中：R1、R2、R3、R4和R5相同或不同，分别代表氢、卤素、C1-C6烷基、C1-C6烷氧基、C1-C4烷硫基、羟基、氨基、单烷基或双烷基(C1-C6)氨基、氰基、硝基、三氟甲基或三氟甲氧基；X代表氧、键、C1-C2烷基或甲氧基亚甲基。这些化合物可用于治疗和/或预防神经心理障碍，包括但不限于精神分裂症、狂躁症、痴呆、抑郁症、焦虑症、强迫症、物质滥用、类帕金森运动障碍和与神经阻滞剂使用相关的运动障碍。

  公开号：

  US06333329B2

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
• 6-(4-arylalkylpiperazin-1-yl) benzodioxane and 6-(4-arylalkypiperazin-1-yl) chromane derivatives: dopamine receptor subtype specific ligands
  申请人：Neurogen Corporation

  公开号：US20020099056A1

  公开（公告）日：2002-07-25

  Disclosed are compounds of the formula: 1 or the pharmaceutically acceptable acid addition salts thereof wherein: R 1 , R 2 , R 3 , R 4 and R 5 are the same or different and represent hydrogen, halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 4 alkylthio, hydroxy, amino, mono- or di(C 1 -C 6 )alkylamino, cyano, nitro, trifluoromethyl or trifluoromethoxy; and X is oxygen, a bond, C 1 -C 2 alkylene, or methyleneoxy, which compounds are useful for the treatment and/or prevention of neuropsychological disorders including, but not limited to, schizophrenia, mania, dementia, depression, anxiety, compulsive behavior, substance abuse, Parkinson-like motor disorders and motion disorders related to the use of neuroleptic agents.

  本发明涉及以下公式的化合物：1或其药学上可接受的酸加盐，其中：R1、R2、R3、R4和R5相同或不同，分别代表氢、卤素、C1-C6烷基、C1-C6烷氧基、C1-C4烷硫基、羟基、氨基、单或双(C1-C6)烷基氨基、氰基、硝基、三氟甲基或三氟甲氧基；且X为氧、键、C1-C2烷基或甲氧基，这些化合物可用于治疗和/或预防神经心理障碍，包括但不限于精神分裂症、躁狂症、痴呆、抑郁症、焦虑症、强迫行为、物质滥用、帕金森样运动障碍和与神经节阻滞剂使用相关的运动障碍。
• PIPERAZINE DERIVATIVE
  申请人：Shionogi&Co., Ltd.

  公开号：EP2184272A1

  公开（公告）日：2010-05-12

  A compound which specifically binds to a receptor of NR1/ NR2B, and is used as a NR2B receptor antagonist is provided. It has been found out that a piperazine derivative represented by the formula (I) binds specifically to a receptor of NR1/NR2B, and is used as a NR2B receptor antagonist. A compound represented by: wherein R1 is each independently C1-C3 alkyl or the like, m is an integer of 0 to 4, X is -N(R4)-C(=O)-C(=O)-, -N(R4)-(CR5R6)p-C(=O)-, -N(R4)-C(-O)-(CR7R8)q- or -C(=O)-N(R4)-(CR7R8)q-, p and q are each independently an integer of 1 to 3, R4, R5, R6, R7 and R8 are each independently a hydrogen atom or lower alkyl, A1 is benzoxazolinone or the like, and A2 is optionally substituted phenyl or the like, or a pharmaceutically acceptable salt or a solvate thereof.

  提供了一种能与 NR1/ NR2B 受体特异性结合并用作 NR2B 受体拮抗剂的化合物。 研究发现，由式（I）代表的哌嗪衍生物能与 NR1/NR2B 受体特异性结合，并可用作 NR2B 受体拮抗剂。 由以下式子代表的化合物 其中 R1 各自独立地为 C1-C3 烷基或类似物，m 为 0 至 4 的整数，X 为-N(R4)-C(＝O)-C(＝O)-、-N(R4)-(CR5R6)p-C(＝O)-、-N(R4)-C(-O)-(CR7R8)q-或-C(＝O)-N(R4)-(CR7R8)q-，p 和 q 各自独立地为 1 至 3 的整数、R4、R5、R6、R7 和 R8 各自独立地为氢原子或低级烷基，A1 为苯并恶唑啉酮或类似物，A2 为任选取代的苯基或类似物，或其药学上可接受的盐或溶液。
• 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