4-[1-(3-chlorophenyl)piperazin-4-yl]cyclohexanone oxime | 223605-20-7

• 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: 4-[1-(3-chlorophenyl)piperazin-4-yl]cyclohexanone oxime
• 英文别名: 4-[4-(3-Chlorophenyl)piperazin-1-yl]cyclohexanone oxime
• CAS: 223605-20-7
• 化学式: C₁₆H₂₂ClN₃O
• 分子量: 307.823
• InChiKey: CUJRGGMVWXAHBO-JXAWBTAJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.23
• 重原子数：
  21.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  39.07
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  4-[1-(3-chlorophenyl)piperazin-4-yl]cyclohexanone oxime 在 platinum(IV) oxide 氢气 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 6.0h， 以57%的产率得到4-[1-(3-chlorophenyl)piperazin-4-yl]cyclohexylamine
  参考文献：
  名称：

  1-Aryl-4-(4-succinimidobutyl)piperazines and their conformationally constrained analogues: synthesis, binding to serotonin (5-HT1A, 5-HT2A, 5-HT7), α1-adrenergic, and dopaminergic D2 receptors, and in vivo 5-HT1A functional characteristics

  摘要：

  Starting with the structure of potent 5-HT1A ligands, that is, MM77 [1-(2-methoxyphenyl)-4-(4-succinimidobutyl)piperazine, 4] and its constrained version 5 (MP349), previously obtained in our laboratory, a series of their direct analogues with differently substituted aromatic ring (R = H, m-Cl, m-CF3, m-OCH3, p-OCH3) were synthesized. The flexible and the corresponding 1e,4e-disubstituted cyclohexane derivatives were designed in order to investigate the influence of rigidification on 5-HT1A affinity, selectivity for 5-HT2A, 5-HT7, D-1, and D-2 binding sites and functional profile at pre- and postsynaptic 5-HT1A receptors. The new compounds 19-25 were found to be highly active 5-HT1A receptor ligands (K-i = 4-44 nM) whereas their affinity for other receptors was: either significantly decreased after rigidification (5-HT7) or controlled by substituents in the aromatic ring (alpha(1)), or influenced by both those structural modifications (5-HT2A), or very low (D-2, K-i = 5.3-31 mu M). Since a distinct disfavor towards rigid compounds was observed for 5-HT7 receptors only, it seems that the bioactive conformation of chain derivatives at those sites should differ from the extended one.Several in vivo models were used to asses functional activity of 19-25 at pre- (hypothermia in mice) and postsynaptic 5-HT1A receptors (lower lip retraction in rats and serotonin syndrome in reserpinized rats). Unlike the parent antagonists 4 and 5, all the new derivatives tested were classified as partial agonists with different potency, however, similar effects were observed within pairs (flexible and rigid) of the analogues. The obtained results indicated that substitution in the aromatic ring, but not spacer rigidification, controls the 5-HT1A functional activity of the investigated compounds. Moreover, an o-methoxy substituent in the structure of 5 seems to be necessary for its full antagonistic properties. Of all the new compounds studied, trans-4-(4-succinimidocyclohexyl)-1-(3-trifluoromethylphenyl)piperazine 24 was the most potent 5-HT1A receptor ligand in vitro (Ki = 4 nM) and in vivo, with at least 100-fold selectivity for the other receptors tested. (c) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.12.041
• 作为产物：
  描述：

  4-[1-(3-chlorophenyl)piperazin-4-yl]cyclohexanone 在 sodium hydroxide 、 盐酸羟胺 作用下， 以 乙醇 、 水 为溶剂， 生成 4-[1-(3-chlorophenyl)piperazin-4-yl]cyclohexanone oxime
  参考文献：
  名称：

  Cyclohexane derivatives difunctionalised in 1,4 as ligands of 5T H1A receptors

  摘要：

  本发明涉及一种新型的1,4-双官能团化环己烷衍生物，其通式为(1)，其中A代表如(IIa)所示的基团，其中Ar本身代表苯基或嘧啶基等芳香结构，可选择性地被一个或多个如C1-C3烷基、C1-C3烷氧基、三氟甲基或卤素等基团取代(IIb)；B代表如下的杂环基团：2位取代的3,5-二氧代-(2H,4H)-1,2,4-三嗪(IIIa)；5位取代的3-氧代-(2H)-1,2,4-三嗪(IIIb)；R代表C1-C3烷基的3,5-二氧代-6-氨基-(2H,4H)-1,2,4-三嗪(IIIc)。本发明还涉及与药学上可接受的酸形成的通式I化合物的盐。此外，本发明还涉及各种“顺式”和“反式”异构体以及具有不对称碳的各种对映异构体。

  公开号：

  US06191130B1

文献信息

• DERIVES CYCLOHEXANIQUES DIFONCTIONNALISES EN 1,4 EN TANT QUE LIGANDS DES RECEPTEURS 5HT1A
  申请人：PIERRE FABRE MEDICAMENT

  公开号：EP1023273B1

  公开（公告）日：2002-06-05
• US6191130B1
  申请人：——

  公开号：US6191130B1

  公开（公告）日：2001-02-20