4-(benzocyclobutan-1-yl)-butyl mesylate

• 分子结构分类: 有机化合物 - 苯类化合物
• 英文名称: 4-(benzocyclobutan-1-yl)-butyl mesylate
• 英文别名: 4-(7-bicyclo[4.2.0]octa-1,3,5-trienyl)butyl methanesulfonate
• 化学式: C₁₃H₁₈O₃S
• 分子量: 254.35
• InChiKey: ZGSKOXZFTIKAOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  51.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2,3-二氢-1,4-苯并二烷-5-基)哌嗪盐酸盐 、 4-(benzocyclobutan-1-yl)-butyl mesylate 在 sodium carbonate 作用下， 以 various solvent(s) 为溶剂， 反应 24.0h， 生成 1-(4-Bicyclo[4.2.0]octa-1(6),2,4-trien-7-yl-butyl)-4-(2,3-dihydro-benzo[1,4]dioxin-5-yl)-piperazine
  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
• 作为产物：
  描述：

  4-(Benzocyclobutan-1-yl)butanol 、 甲基磺酰氯 、 三乙胺 以 二氯甲烷 为溶剂， 生成 4-(benzocyclobutan-1-yl)-butyl mesylate
  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

文献信息

• US5194437A
  申请人：——

  公开号：US5194437A

  公开（公告）日：1993-03-16
• Characterization of Potent and Selective Antagonists at Postsynaptic 5-HT1A Receptors in a Series of N4-Substituted Arylpiperazines
  作者：Jean-Louis Peglion、Herve Canton、Karin Bervoets、Valerie Audinot、Mauricette Brocco、Alain Gobert、Sylvie Le Marouille-Girardon、Mark J. Millan

  DOI：10.1021/jm00020a020

  日期：1995.9

  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.
• 1,4-disubstituted piperazines
  申请人：Adir et Compagnie

  公开号：US05194437A1

  公开（公告）日：1993-03-16

  The compounds are 1,4-disubstituted piperazines useful for the treatment of disorders of central nervous system and neuroendocrine disorders. A compound disclosed is (R,S)-4-(benzodioxan-5-yl)-1-[(benzocyclobutan-1-yl)methyl]piperazine.

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