1-(2,3-二氢-1,4-苯并二恶英-5-基)-4-(2,3-二氢-1H-茚满-2-基)哌嗪 | 146998-34-7

• 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-1,4-苯并二恶英-5-基)-4-(2,3-二氢-1H-茚满-2-基)哌嗪
• 英文名称: 1-(2,3-dihydro-1,4-benzodioxin-5-yl)-4-(indan-2-yl)piperazine
• 英文别名: S 15535；(4-benzodioxan-5-yl)-1-(indan-2-yl)piperazine；4-(Benzodioxan-5-yl)-1-(indan-2-yl)piperazine；1-(2,3-dihydro-1,4-benzodioxin-5-yl)-4-(2,3-dihydro-1H-inden-2-yl)piperazine
• CAS: 146998-34-7
• 化学式: C₂₁H₂₄N₂O₂
• 分子量: 336.434
• InChiKey: QJPPEMXOOWNICQ-UHFFFAOYSA-N

物化性质

• 沸点：
  504.5±50.0 °C(Predicted)
• 密度：
  1.228±0.06 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：~6 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  24.9
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 储存条件：
  2-8℃

制备方法与用途

S-15535是一种高选择性5-HT1A受体配体，既可作为突触后5-HT1A受体的拮抗剂，也可作为突触前5-HT1A受体的激动剂。它可用于研究精神疾病，如抗焦虑作用。

反应信息

• 作为反应物：
  描述：

  1-(2,3-二氢-1,4-苯并二恶英-5-基)-4-(2,3-二氢-1H-茚满-2-基)哌嗪 、 2-茚满基对甲苯磺酸盐 生成 1-(2,3-二氢-1,4-苯并二烷-5-基)哌嗪盐酸盐
  参考文献：
  名称：

  1,4-disubstituted piperazines

  摘要：

  这个化合物是1,4-二取代哌嗪类化合物，可用于治疗中枢神经系统和神经内分泌紊乱。其中一种化合物是(R,S)-4-(苯并二氧杂环[3.2.1]辛-5-基)-1-[(苯并环丁烷-1-基)甲基]哌嗪。

  公开号：

  US05194437A1
• 作为产物：
  描述：

  5-氨基-1,4-苯并二恶烷 在 sodium carbonate 、 potassium carbonate 作用下， 以 氯苯 为溶剂， 反应 48.0h， 生成 1-(2,3-二氢-1,4-苯并二恶英-5-基)-4-(2,3-二氢-1H-茚满-2-基)哌嗪
  参考文献：
  名称：

  Characterization of Potent and Selective Antagonists at Postsynaptic 5-HT1A Receptors in a Series of N4-Substituted Arylpiperazines

  摘要：

  Benzocycloalkyl and benzocycloalkenyl moities linked, directly or via an alkyl chain, to oxygen-bearing heteroarylpiperazines were synthesized, in an attempt to obtain potent and selective antagonists at postsynaptic 5-HT1A receptors. From the numerous arylpiperazines described in the literature, 1-(2,3-dihydro-1,4-benzodioxin-5-yl)pipe (3a) was chosen as a model of an arylpiperazine in view of its selectivity for 5-HT1A receptors versus alpha(1)-, alpha(2)-, and beta-adrenergic receptors, as well as dopamine D-1 and D-2 receptors. Two other closely-related arylpiperazines, 1-(1,5-benzodioxepin-6-yl)piperazine (3b) and 1-(benzofuran-7-yl)piperazine (3c), were also examined in this study. Al compounds showed high affinity at 5-HT1A sites (8.10 less than or equal to pK(i)s less than or equal to 9.35), and the majority behaved as antagonists in vivo in blocking the hypothermia induced by the 5-HT1A agonist 8-OH-DPAT in the absence of a marked effect alone at equivalent doses. An in vivo evaluation of dopamine D-2 receptor antagonist properties revealed that the majority of compounds was devoid of activity at this site, in marked contrast to BMY 7378 which displayed virtually no selectivity for 5-HT1A versus dopamine D-2 receptors. Moreover, six compounds of the present series, 8, 10, 11, 14, 25, and, 37, showed > 10-fold selectivity in vitro for 5-HT1A versus alpha(1)-adrenergic receptors. Compound 14 displayed an optimal compromise between potency (pK(i) = 8.75), marked antagonist activity, and selectivity toward alpha(1)-adrenergic (81-fold) and dopamine D-2 (195-fold) receptors. These characteristics clearly distinguish 14 from previously-reported ligands such as the postsynaptic 5-HT1A antagonist BMY 7378 and the weak partial agonist NAN 190 which, in contrast to the compounds of this series, belong to the well-exemplified class of imido derivatives of (o-methoxyphenyl)piperazines. The availability of 14 (S 15535) should facilitate the further elucidation of the functional role and potential therapeutic significance of 5-HT1A receptors.

  DOI：

  10.1021/jm00020a020

文献信息

• Piperazines 1,4-disubstiuées, leur procédé de préparation et les compositions pharmaceutiques les renfermant
  申请人：ADIR ET COMPAGNIE

  公开号：EP0490772A1

  公开（公告）日：1992-06-17

  Nouvelles pipérazines 1,4-disubsituées, utilisables comme médicament et répondant à la formule : dans laquelle : X1, X2, X3, R1, E -, m, p et -A-B- ont les significations définies dans la description, sous formes racémiques et optiquement actives ; Ces dérivés et leurs sels physiologiquement tolérables peuvent être utilisés en thérapeutique notamment dans le traitement des maladies du système nerveux central et des maladies neuroendocriniennes.

  可用作药物的、与式......对应的新型 1,4-二取代哌嗪 其中： X1，X2，X3，R1，E-、 m、p 和 -A-B- 具有说明中定义的含义，具有外消旋和光学活性形式； 这些衍生物及其生理上可耐受的盐类可用于治疗，特别是治疗中枢神经系统疾病和神经内分泌疾病。
• FMO3 inhibitors for treating pain
  申请人：Akron Molecules GmbH

  公开号：EP2674161A1

  公开（公告）日：2013-12-18

  The present invention relates to new therapies to treat pain and related diseases, as well as pharmaceutical compounds for use in said therapies.

  本发明涉及治疗疼痛和相关疾病的新疗法，以及用于上述疗法的药物化合物。
• ENGAGING THE CERVICAL SPINAL CORD CIRCUITRY TO RE- ENABLE VOLITIONAL CONTROL OF HAND FUNCTION IN TETRAPLEGIC SUBJECTS
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：EP3782698A1

  公开（公告）日：2021-02-24

  In various embodiments, methods are provided for applying transcutaneous and/or epidural spinal cord stimulation with and without selective pharmaceuticals to restore voluntary control of hand function in tetraplegic subjects.

  在各种实施方案中，提供了使用或不使用选择性药物的经皮和/或硬膜外脊髓刺激方法，以恢复四肢瘫痪者对手部功能的自主控制。
• Engaging the cervical spinal cord circuitry to re-enable volitional control of hand function in tetraplegic subjects
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US10137299B2

  公开（公告）日：2018-11-27

  In various embodiments, methods are provided for applying transcutaneous and/or epidural spinal cord stimulation with and without selective pharmaceuticals to restore voluntary control of hand function in tetraplegic subjects.

  在各种实施方案中，提供了使用或不使用选择性药物的经皮和/或硬膜外脊髓刺激方法，以恢复四肢瘫痪者对手部功能的自主控制。
• Methods of fabricating a multi-electrode array for spinal cord epidural stimulation
  申请人：The Regents of the University of California

  公开号：US10583285B2

  公开（公告）日：2020-03-10

  In certain embodiments an electrode array for epidural stimulation of the spinal cord is provided where the array comprises a plurality of electrodes disposed on a flexible polymer substrate; said electrodes being electrically connected to one or more lead wires and/or connection points on an electrical connector; where the electrodes of said array are bonded to said polymer so that the electrodes can carry an electrical stimulation signal having a voltage, frequency, and current sufficient to provide epidural stimulation of a spinal cord and/or brain in vivo or in a physiological saline solution, without separation of all or a part of an electrode from the polymer substrate.

  在某些实施方案中，提供了一种用于脊髓硬膜外刺激的电极阵列，该阵列包括多个电极，这些电极布置在柔性聚合物基板上；所述电极与电连接器上的一根或多根导线和/或连接点电连接；所述阵列的电极与所述聚合物粘合，使电极能够携带具有足够电压、频率和电流的电刺激信号，以便在体内或生理盐水溶液中对脊髓和/或大脑进行硬膜外刺激，而不会使电极的全部或部分与聚合物基底分离。