(R)-{2-[4-(2-methoxyphenyl)-piperazin-1-yl]-1-methyl-ethyl}-amine | 133025-57-7

• 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: (R)-{2-[4-(2-methoxyphenyl)-piperazin-1-yl]-1-methyl-ethyl}-amine
• 英文别名: (R)-(1-(2-aminopropyl))-4-(2-methoxyphenyl)piperazine；(R)-1-methyl-2-[4-(2-methoxyphenyl)-piperazinyl]ethylamine；(2R)-1-[4-(2-methoxyphenyl)piperazin-1-yl]propan-2-amine
• CAS: 133025-57-7
• 化学式: C₁₄H₂₃N₃O
• mdl: MFCD25909152
• 分子量: 249.356
• InChiKey: OVRJUXJXYNVTLQ-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.571
• 拓扑面积：
  41.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-金刚烷甲酸 、 (R)-{2-[4-(2-methoxyphenyl)-piperazin-1-yl]-1-methyl-ethyl}-amine 在 N-甲基吗啉 、 氰基磷酸二乙酯 作用下， 以 二氯甲烷 为溶剂， 生成 (R)-adamantane-1-carboxylic acid N-[1-methyl-2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]carboxamide
  参考文献：
  名称：

  Synthesis and SAR of Adatanserin:  Novel Adamantyl Aryl- and Heteroarylpiperazines with Dual Serotonin 5-HT_1A and 5-HT₂ Activity as Potential Anxiolytic and Antidepressant Agents

  摘要：

  Several novel functionalized adamantyl aryl- and heteroarylpiperazine derivatives were prepared and examined in various receptor binding and behavioral tests to determine their serotonin receptor activities. Many compounds demonstrated modest to high affinity for 5-HT1A receptors, with compounds 9, 13, 23, 33, 34, and 43 being the most potent at this site. Compound 1, 2-[4-(2-pyrimidinyl)-1-piperazinyl] ethyl adamantyl-1-carboxylate, demonstrated relatively high affinity for 5-HT1A receptors (K-i = 8 nM) and acceptable selectivity versus D-2 receptors (K-i = 708 mM); however, it lacked in vivo activity in serotonergic behavioral models. In contrast, compounds 9 (WY-50,324, SEB-324, adatanserin), adamantyl-1-carboxylic acid 2-[4-(2-pyrimidinyl)-1-piperazinyl]ethylamide, and 13, adamantyl-1-carboxylic acid 2-[4-(2-methoxyphenyl)-1-piperazinyl] ethylamide, demonstrated high affinity for 5-HT1A binding sites (K-i = 1 nM for both) and moderate affinity for 5-HT2 receptors (K-i = 73 and 75 nM, respectively). Both compounds also demonstrated partial 5-HT1A agonist activity in vivo in rat serotonin syndrome and 5-HT2 antagonist activity in quipazine- and DOI-induced head shake paradigms. The selective 5-HT1A partial agonist and 5-HT2 antagonist activity of 9 was accompanied by significant anxiolytic activity in an animal conflict model. On the basis of this profile, compound 9 entered development as a combined anxiolytic and antidepressant agent.

  DOI：

  10.1021/jm9806704
• 作为产物：
  描述：

  (R)-2-Amino-1-[4-(2-methoxy-phenyl)-piperazin-1-yl]-propan-1-one; compound with GENERIC INORGANIC NEUTRAL COMPONENT 在 硼烷 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以87%的产率得到(R)-{2-[4-(2-methoxyphenyl)-piperazin-1-yl]-1-methyl-ethyl}-amine
  参考文献：
  名称：

  Synthesis and SAR of Adatanserin:  Novel Adamantyl Aryl- and Heteroarylpiperazines with Dual Serotonin 5-HT_1A and 5-HT₂ Activity as Potential Anxiolytic and Antidepressant Agents

  摘要：

  Several novel functionalized adamantyl aryl- and heteroarylpiperazine derivatives were prepared and examined in various receptor binding and behavioral tests to determine their serotonin receptor activities. Many compounds demonstrated modest to high affinity for 5-HT1A receptors, with compounds 9, 13, 23, 33, 34, and 43 being the most potent at this site. Compound 1, 2-[4-(2-pyrimidinyl)-1-piperazinyl] ethyl adamantyl-1-carboxylate, demonstrated relatively high affinity for 5-HT1A receptors (K-i = 8 nM) and acceptable selectivity versus D-2 receptors (K-i = 708 mM); however, it lacked in vivo activity in serotonergic behavioral models. In contrast, compounds 9 (WY-50,324, SEB-324, adatanserin), adamantyl-1-carboxylic acid 2-[4-(2-pyrimidinyl)-1-piperazinyl]ethylamide, and 13, adamantyl-1-carboxylic acid 2-[4-(2-methoxyphenyl)-1-piperazinyl] ethylamide, demonstrated high affinity for 5-HT1A binding sites (K-i = 1 nM for both) and moderate affinity for 5-HT2 receptors (K-i = 73 and 75 nM, respectively). Both compounds also demonstrated partial 5-HT1A agonist activity in vivo in rat serotonin syndrome and 5-HT2 antagonist activity in quipazine- and DOI-induced head shake paradigms. The selective 5-HT1A partial agonist and 5-HT2 antagonist activity of 9 was accompanied by significant anxiolytic activity in an animal conflict model. On the basis of this profile, compound 9 entered development as a combined anxiolytic and antidepressant agent.

  DOI：

  10.1021/jm9806704

文献信息

• N-((phenyl, benzodioxinyl or
  申请人：John Wyeth & Brother, Ltd.

  公开号：US06127357A1

  公开（公告）日：2000-10-03

  Piperazine derivatives of formula I ##STR1## and their pharmaceutically acceptable acid addition salts are 5-HT.sub.1A binding agents, particularly 5-HT.sub.1A antagonists and may be used, for example, as anxiolytics. In the formula A is C.sub.2-4 alkylene chain optionally substituted by lower alkyl, Z is oxygen or sulphur, R is hydrogen or lower alkyl, R.sup.1 is a mono or bicyclic aryl or heteroaryl radical, R.sup.2 is a mono or bicyclic heteroaryl radical and R.sup.3 is hydrogen or a specified radical such as lower alkyl, cycloalkyl, aryl, heteroaryl or optionally substituted amino.

  Piperazine derivatives of formula I ##STR1##及其药用可接受的酸盐是5-HT.sub.1A结合剂，特别是5-HT.sub.1A拮抗剂，例如可用作抗焦虑药。在该式中，A为C.sub.2-4烷基链，可选择性地被较低烷基取代，Z为氧或硫，R为氢或较低烷基，R.sup.1为单环或双环芳基或杂芳基基团，R.sup.2为单环或双环杂芳基基团，R.sup.3为氢或指定的基团，如较低烷基、环烷基、芳基、杂芳基或可选择性取代的氨基。
• Tertiary alkyl functionalized piperazine derivatives
  申请人：American Home Products Corp.

  公开号：US04988814A1

  公开（公告）日：1991-01-29

  Compounds of the formula: ##STR1## in which R.sup.1 is alkyl; R.sup.2 and R.sup.3 are alkyl or taken together they are polymethylene, R.sup.2 and R.sup.3 complete a 5-norbornen-2-yl moiety; X is --CO.sub.2 --, --OCO--, --OCO.sub.2 --, --N(R.sup.7)CO--, --NHNHCO--, --ON(R.sup.7)CO--, --CON(R.sup.7)--, --N(R.sup.7)CO.sub.2 --, --OCON(R.sup.7)-- or --N(R.sup.7)CON(R.sup.8)--, wherein R.sup.7 and R.sup.8 are, independently, hydrogen, alkyl, phenyl, benzyl, substituted phenyl or substituted benzyl in which the substituents are halo, alkyl alkoxy, cyano, nitro or perhalomethyl; R.sup.4 is hydrogen or alkyl; R.sup.5 is hydrogen, alkyl, hydroxyalkyl, phenyl, benzyl, substituted phenyl or substituted benzyl in which the substituents are hydroxy, halo, alkyl alkoxy, trifluoromethyl, nitro, cyano, carbalkoxy, carboxamido, amino, alkylamino or dialkylamino; R.sup.6 is phenyl, benzyl, 2-, 3-, or 4-pyridinyl, 2-pyrimidinyl or 2-pyrazinyl any of which may be substituted by one or more hydroxy, halo, alkyl alkoxy, trifluoromethyl, nitro, cyano, carbalkoxy, carboxamido, amino, alkylamino or dialkylamino; n is one of the integers 0, 1, 2, 3, 4 or 5; or a pharmaceutically acceptable salt thereof, with the proviso that when X is --CON(R.sup.7)-- and R.sup.7 is alkyl, R.sup.6 is other than 2-pyrimidinyl, and when X is --CO.sub.2 -- and R.sup.1, R.sup.2 and R.sup.3 are methyl and n is 1, R.sup.6 is other than 3,5-di(trifluoromethyl)phenyl are antidepressant and/or anxiolytic agents.

  化合物的公式为：##STR1## 其中R.sup.1是烷基; R.sup.2和R.sup.3是烷基或共同构成聚亚甲基，R.sup.2和R.sup.3形成5-去氢萘-2-基基团; X是--CO.sub.2 --，--OCO--，--OCO.sub.2 --，--N(R.sup.7)CO--，--NHNHCO--，--ON(R.sup.7)CO--，--CON(R.sup.7)--，--N(R.sup.7)CO.sub.2 --，--OCON(R.sup.7)--或--N(R.sup.7)CON(R.sup.8)--，其中R.sup.7和R.sup.8分别是氢，烷基，苯基，苄基，取代苯基或取代苄基，其中取代基是卤素，烷氧基，氰基，硝基或全氟甲基; R.sup.4是氢或烷基; R.sup.5是氢，烷基，羟基烷基，苯基，苄基，取代苯基或取代苄基，其中取代基是羟基，卤素，烷氧基，三氟甲基，硝基，氰基，碳酸烷酯，羧酰胺，氨基，烷基氨基或二烷基氨基; R.sup.6是苯基，苄基，2-, 3-, 或4-吡啶基，2-嘧啶基或2-吡嗪基，其中任何一个可能被一个或多个羟基，卤素，烷氧基，三氟甲基，硝基，氰基，碳酸烷酯，羧酰胺，氨基，烷基氨基或二烷基氨基取代; n是0、1、2、3、4或5中的一个整数; 或其药学上可接受的盐，但当X是--CON(R.sup.7)--且R.sup.7是烷基时，R.sup.6不是2-嘧啶基，当X是--CO.sub.2 --且R.sup.1，R.sup.2和R.sup.3是甲基且n为1时，R.sup.6不是3,5-二(三氟甲基)苯基，这些化合物是抗抑郁和/或抗焦虑药物。
• N-substituted imide derivatives with serotonergic activity
  申请人：American Home Products Corporation

  公开号：US20020013324A1

  公开（公告）日：2002-01-31

  Compounds of the Formula (I) 1 wherein R 2 , Y, X and n are as defined in the specification which compounds are useful in the treatment of disorders associated with serotonergic neuron-related diseases.

  式(I)的化合物，其中R2，Y，X和n如规范所定义，这些化合物对治疗与5-羟色胺神经元相关疾病有关的障碍非常有用。
• Piperazine derivatives
  申请人：JOHN WYETH & BROTHER LIMITED

  公开号：EP0512755A2

  公开（公告）日：1992-11-11

  Piperazine derivatives of formula I and their pharmaceutically acceptable acid addition salts are 5-HTIA binding agents, particularly 5-HTIA antagonists and may be used, for example, as anxiolytics. In the formula A is C2-4 alkylene chain optionally substituted by lower alkyl, Z is oxygen or sulphur, R is hydrogen or lower alkyl, R1 is a mono or bicyclic aryl or heteroaryl radical, R2 is a mono or bicyclic heteroaryl radical and R3 is hydrogen or a specified radical such as lower alkyl, cycloalkyl, aryl, heteroaryl or optionally substituted amino.

  式 I 的哌嗪衍生物 及其药学上可接受的酸加成盐是 5-HTIA 结合剂，特别是 5-HTIA 拮抗剂，可用作抗焦虑药等。在式中，A 是任选被低级烷基取代的 C2-4 烷链，Z 是氧或硫，R 是氢或低级烷基，R1 是单环或双环芳基或杂芳基，R2 是单环或双环杂芳基，R3 是氢或特定的基，如低级烷基、环烷基、芳基、杂芳基或任选取代的氨基。
• US4988814A
  申请人：——

  公开号：US4988814A

  公开（公告）日：1991-01-29