2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethan-1-amine | 676115-71-2

• 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: 2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethan-1-amine
• 英文别名: {2-[4-(1,2-Benzisothiazol-3-yl)piperazin-1-yl]ethyl}amine；2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethanamine
• CAS: 676115-71-2
• 化学式: C₁₃H₁₈N₄S
• 分子量: 262.379
• InChiKey: OUQWEASCLQYFGL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  73.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  间甲苯磺酰氯 、 2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethan-1-amine 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以49%的产率得到N-(2-(4-(1,2-benzothiazol-3-yl)piperazin-1-yl)ethyl)-3-methylbenzenesulphonamide
  参考文献：
  名称：

  Novel Arylsulfonamide Derivatives with 5-HT₆/5-HT₇ Receptor Antagonism Targeting Behavioral and Psychological Symptoms of Dementia

  摘要：

  In order to target behavioral and psychological symptoms of dementia (BPSD), we used molecular modeling-assisted design to obtain novel multifunctional arylsulfonamide derivatives that potently antagonize 5-HT6/7/2A and D-2 receptors, without interacting with M-1 receptors and hERG channels. In vitro studies confirmed their antagonism of 5-HT7/2A and D-2 receptors and weak interactions with key antitargets (M1R and hERG) associated with side effects. Marked 5-HT6 receptor affinities were also observed, notably for 6-fluoro-3-(piperidin-4-yl)-1,2-benzoxazole derivatives connected by a 3-4 unit alkyl linker with mono- or bicyclic, lipophilic arylsulfonamide moieties. N-[4-[4-(6-Fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]butyl]benzothiophene-2-sulfonamide (72) was characterized in vitro on 14 targets and antitargets. It displayed dual blockade of 5-HT6 and D-2 receptors and negligible interactions at hERG and M-1 receptors. Unlike reference antipsychotics, 72 displayed marked antipsychotic and antidepressant activity in rats after oral administration, in the absence of cognitive or motor impairment. This profile is particularly attractive when targeting a fragile, elderly BPSD patient population.

  DOI：

  10.1021/jm401895u
• 作为产物：
  描述：

  N-<2-<4-(1,2-benzisothiazol-3-yl)-1-piperazinyl>ethyl>phthalimide 在 水 、 甲胺 作用下， 反应 72.0h， 生成 2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethan-1-amine
  参考文献：
  名称：

  Novel Arylsulfonamide Derivatives with 5-HT₆/5-HT₇ Receptor Antagonism Targeting Behavioral and Psychological Symptoms of Dementia

  摘要：

  In order to target behavioral and psychological symptoms of dementia (BPSD), we used molecular modeling-assisted design to obtain novel multifunctional arylsulfonamide derivatives that potently antagonize 5-HT6/7/2A and D-2 receptors, without interacting with M-1 receptors and hERG channels. In vitro studies confirmed their antagonism of 5-HT7/2A and D-2 receptors and weak interactions with key antitargets (M1R and hERG) associated with side effects. Marked 5-HT6 receptor affinities were also observed, notably for 6-fluoro-3-(piperidin-4-yl)-1,2-benzoxazole derivatives connected by a 3-4 unit alkyl linker with mono- or bicyclic, lipophilic arylsulfonamide moieties. N-[4-[4-(6-Fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]butyl]benzothiophene-2-sulfonamide (72) was characterized in vitro on 14 targets and antitargets. It displayed dual blockade of 5-HT6 and D-2 receptors and negligible interactions at hERG and M-1 receptors. Unlike reference antipsychotics, 72 displayed marked antipsychotic and antidepressant activity in rats after oral administration, in the absence of cognitive or motor impairment. This profile is particularly attractive when targeting a fragile, elderly BPSD patient population.

  DOI：

  10.1021/jm401895u

文献信息

• <i>N</i>-(4-Arylpiperazinoalkyl)acetamide derivatives of 1,3- and 3,7-dimethyl-1<i>H</i>-purine-2,6(3<i>H</i>,7<i>H</i>)-diones and their 5-HT₆, 5-HT₇, and D₂ receptors affinity
  作者：Paweł Żmudzki、Grzegorz Satała、Grażyna Chłoń-Rzepa、Andrzej J. Bojarski、Piotr Popik、Paweł Zajdel

  DOI：10.1515/hc-2014-0200

  日期：2015.2.1

  A series of N-(arylpiperazinyl)acetamide derivatives of 1,3- and 3,7-dimethyl-1H-purine-2,6(3H,7H)-dione was synthesized and biologically evaluated in in vitro competition binding experiments for serotonin 5-HT₆, 5-HT₇, and dopamine D₂ receptors. The structure-affinity relationships for this group of compounds allowed for determination of structural features responsible for receptor affinity. Among the investigated derivatives, compounds 5 and 12 with (2,3-dichlorophenyl)piperazine moiety were classified as potent dual 5-HT₆/D₂ receptors ligands, whereas compound 4, with 4-(benzo[d]isothiazol-3-yl)piperazine moiety, and compounds 8 and 15, with (2,3-dichlorophenyl)piperazine moiety, were classified as potent D₂ receptor ligands.

  合成了一系列N-(芳基哌嗪基)乙酰胺衍生物，包括1,3-二甲基-1H-嘌呤-2,6(3H,7H)-二酮和3,7-二甲基-1H-嘌呤-2,6(3H,7H)-二酮，并在体外竞争结合实验中对其进行了生物学评价，涉及5-羟色胺5-HT₆、5-HT₇和多巴胺D₂受体。这组化合物的结构-亲和力关系使得能够确定负责受体亲和力的结构特征。在研究的衍生物中，含有(2,3-二氯苯基)哌嗪基团的化合物5和12被归类为强效的双重5-HT₆/D₂受体配体，而含有4-(苯并[d]异噻唑-3-基)哌嗪基团的化合物4，以及含有(2,3-二氯苯基)哌嗪基团的化合物8和15，被归类为强效的D₂受体配体。

• [EN] ARYLOSULFONAMIDES FOR THE TREATMENT OF CNS DISEASES<br/>[FR] ARYLSULFAMIDES POUR LE TRAITEMENT DE MALADIES DU SNC
  申请人：ADAMED SP ZOO

  公开号：WO2012035123A1

  公开（公告）日：2012-03-22

  Arylsulphonamide derivatives of formula (I) and pharmaceutically acceptable salts thereof. The compounds may be useful for the treatment and/or prevention of disorders of the central nervous system.

  化学式（I）的芳基磺酰胺衍生物及其药用盐。这些化合物可能对中枢神经系统的治疗和/或预防具有用处。
• ARYLOSULFONAMIDES FOR THE TREATMENT OF CNS DISEASES
  申请人：Kolaczkowski Marcin

  公开号：US20130172365A1

  公开（公告）日：2013-07-04

  Arylsulphonamide derivatives of formula (I) and pharmaceutically acceptable salts thereof. The compounds may be useful for the treatment and/or prevention of disorders of the central nervous system.

  化学式（I）的芳基磺胺衍生物及其药用盐。这些化合物可能对中枢神经系统疾病的治疗和/或预防有用。
• US8822517B2
  申请人：——

  公开号：US8822517B2

  公开（公告）日：2014-09-02
• US9120767B2
  申请人：——

  公开号：US9120767B2

  公开（公告）日：2015-09-01