N-isopropyl-4-(2-pyrimidinyl)-1-piperazineethanamine | 143053-01-4

• 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: N-isopropyl-4-(2-pyrimidinyl)-1-piperazineethanamine
• 英文别名: N-(1-methylethyl)-2-[4-(2-pyrimidinyl)-1-piperazinyl]ethylamine；N-[2-(4-pyrimidin-2-ylpiperazin-1-yl)ethyl]propan-2-amine
• CAS: 143053-01-4
• 化学式: C₁₃H₂₃N₅
• 分子量: 249.359
• InChiKey: NSBZRRCRZALINZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  44.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  金刚烷酰氯 、 N-isopropyl-4-(2-pyrimidinyl)-1-piperazineethanamine 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 adamanatne-1-carboxylic acid N-[2-[4-(2-pyrimidinyl)-1-piperazinyl]ethyl]-N-isopropylcarboxamide
  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：

  cyanoborane 、 2-(4-(嘧啶-2-基)哌嗪-1-基)乙胺 在 氯化锌 sodium hydroxide 、 sodium cyanoborohydride 作用下， 以 甲醇 、 二氯甲烷 、 丙酮 为溶剂， 以50%的产率得到N-isopropyl-4-(2-pyrimidinyl)-1-piperazineethanamine
  参考文献：
  名称：

  Use of aryl- and heteroaryl piperazinyl carboxamides in the treatment of

  摘要：

  公开了使用式(I)的化合物，其中R.sup.1为1-金刚烷基、3-甲基-1-金刚烷基、3-去金刚烷基、未取代或取代的2-吲哚基、3-吲哚基、2-苯并呋喃基或3-苯并呋喃基，其中取代基选自较低的烷基、较低的烷氧基和卤素；R.sup.2为未取代或取代的苯基、苄基或嘧啶基，其中取代基选自较低的烷基、较低的烷氧基、三氟甲基和卤素；R.sup.3为H或1至3个碳原子的较低烷基；n为整数0或1；m为2至5的整数及其药用盐。

  公开号：

  US05106849A1

文献信息

• US5106849A
  申请人：——

  公开号：US5106849A

  公开（公告）日：1992-04-21
• US5278160A
  申请人：——

  公开号：US5278160A

  公开（公告）日：1994-01-11
• US5482940A
  申请人：——

  公开号：US5482940A

  公开（公告）日：1996-01-09
• 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
  作者：Magid A. Abou-Gharbia、Wayne E. Childers、Horace Fletcher、Georgia McGaughey、Usha Patel、Michael B. Webb、John Yardley、Terrance Andree、Carl Boast、Robert J. Kucharik、Karen Marquis、Herman Morris、Rosemary Scerni、John A. Moyer

  DOI：10.1021/jm9806704

  日期：1999.12.1

  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.
• Use of aryl- and heteroaryl piperazinyl carboxamides in the treatment of
  申请人：American Home Products Corporation

  公开号：US05106849A1

  公开（公告）日：1992-04-21

  There are disclosed the use of the compounds of the formula (I) ##STR1## wherein R.sup.1 is 1-adamantyl, 3-methyl-1-adamantyl, 3-noradamantyl, unsubstituted or substituted-2-indolyl, 3-indolyl, 2-benzofuranyl or 3-benzofuranyl wherein the substituents are selected from lower alkyl, lower alkoxy and halo; R.sup.2 is unsubstituted or substituted phenyl, benzyl, or pyrimidinyl wherein the substituents are selected from lower alkyl, lower alkoxy, trifluoromethyl and halo; R.sup.3 is H or lower alkyl of 1 to 3 carbon atoms; n is the integer 0 or 1; and m is the integer from 2 to 5 and the pharmaceutically acceptable salts thereof.

  公开了使用式(I)的化合物，其中R.sup.1为1-金刚烷基、3-甲基-1-金刚烷基、3-去金刚烷基、未取代或取代的2-吲哚基、3-吲哚基、2-苯并呋喃基或3-苯并呋喃基，其中取代基选自较低的烷基、较低的烷氧基和卤素；R.sup.2为未取代或取代的苯基、苄基或嘧啶基，其中取代基选自较低的烷基、较低的烷氧基、三氟甲基和卤素；R.sup.3为H或1至3个碳原子的较低烷基；n为整数0或1；m为2至5的整数及其药用盐。