8-Chlor-11-(N-ethylpiperazino)-5H-dibenzo-1,4-diazepin | 5747-61-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 8-Chlor-11-(N-ethylpiperazino)-5H-dibenzo-1,4-diazepin
• 英文别名: 8-chloro-11-(4-ethyl-piperazin-1-yl)-5H-dibenzo[b,e][1,4]diazepine；3-chloro-6-(4-ethylpiperazin-1-yl)-11H-benzo[b][1,4]benzodiazepine
• CAS: 5747-61-5
• 化学式: C₁₉H₂₁ClN₄
• 分子量: 340.856
• InChiKey: BDMWELNCLZHBOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  30.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-Chlor-11-(N-ethylpiperazino)-5H-dibenzo-1,4-diazepin 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 以70%的产率得到4-(8-chloro-5H-dibenzo[b,e][1,4]diazepin-11-yl)-1-ethylpiperazine N-oxide
  参考文献：
  名称：

  The First Structure–Activity Relationship Studies for Designer Receptors Exclusively Activated by Designer Drugs

  摘要：

  Over the past decade, two independent technologies have emerged and been widely adopted by the neuroscience community for remotely controlling neuronal activity: optogenetics which utilize engineered channelrhodopsin and other opsins, and chemogenetics which utilize engineered G protein-coupled receptors (Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)) and other orthologous ligand receptor pairs. Using directed molecular evolution, two types of DREADDs derived from human muscarinic acetylcholine receptors have been developed: hM3Dq which activates neuronal firing, and hM4Di which inhibits neuronal firing. Importantly, these DREADDs were not activated by the native ligand acetylcholine (ACh), but selectively activated by dozapine N-oxide (CNO), a pharmacologically inert ligand. CNO has been used extensively in rodent models to activate DREADDs, and although CNO is not subject to significant metabolic transformation in mice, a small fraction of CNO is apparently metabolized to clozapine in humans and guinea pigs, lessening the translational potential of DREADDs. To effectively translate the DREADD technology, the next generation of DREADD agonists are needed and a thorough understanding of structure activity relationships (SARs) of DREADDs is required for developing such ligands. We therefore conducted the first SAR studies of hM3Dq. We explored multiple regions of the scaffold represented by CNO, identified interesting SAR trends, and discovered several compounds that are very potent hM3Dq agonists but do not activate the native human M3 receptor (hM3). We also discovered that the approved drug perlapine is a novel hM3Dq agonist with >10 000-fold selectivity for hM3Dq over hM3.

  DOI：

  10.1021/cn500325v
• 作为产物：
  描述：

  8-氯-5,10-二氢-11H-二苯并[b,e][1,4]二氮杂卓-11-酮 在 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 4.0h， 生成 8-Chlor-11-(N-ethylpiperazino)-5H-dibenzo-1,4-diazepin
  参考文献：
  名称：

  The First Structure–Activity Relationship Studies for Designer Receptors Exclusively Activated by Designer Drugs

  摘要：

  Over the past decade, two independent technologies have emerged and been widely adopted by the neuroscience community for remotely controlling neuronal activity: optogenetics which utilize engineered channelrhodopsin and other opsins, and chemogenetics which utilize engineered G protein-coupled receptors (Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)) and other orthologous ligand receptor pairs. Using directed molecular evolution, two types of DREADDs derived from human muscarinic acetylcholine receptors have been developed: hM3Dq which activates neuronal firing, and hM4Di which inhibits neuronal firing. Importantly, these DREADDs were not activated by the native ligand acetylcholine (ACh), but selectively activated by dozapine N-oxide (CNO), a pharmacologically inert ligand. CNO has been used extensively in rodent models to activate DREADDs, and although CNO is not subject to significant metabolic transformation in mice, a small fraction of CNO is apparently metabolized to clozapine in humans and guinea pigs, lessening the translational potential of DREADDs. To effectively translate the DREADD technology, the next generation of DREADD agonists are needed and a thorough understanding of structure activity relationships (SARs) of DREADDs is required for developing such ligands. We therefore conducted the first SAR studies of hM3Dq. We explored multiple regions of the scaffold represented by CNO, identified interesting SAR trends, and discovered several compounds that are very potent hM3Dq agonists but do not activate the native human M3 receptor (hM3). We also discovered that the approved drug perlapine is a novel hM3Dq agonist with >10 000-fold selectivity for hM3Dq over hM3.

  DOI：

  10.1021/cn500325v

文献信息

• NOVEL PSYCHOTROPIC AGENTS HAVING GLUTAMATE NMDA ACTIVITY
  申请人：Portnoy Moshe

  公开号：US20100093704A1

  公开（公告）日：2010-04-15

  The invention provides novel compounds and pharmaceutical compositions for the treatment of psychological and/or psychiatric diseases or disorders.

  本发明提供了用于治疗心理和/或精神疾病或障碍的新化合物和制药组合物。
• DREADD ACTUATORS
  申请人：The United States of America,as represented by the Secretary,Department of Health and Human Services

  公开号：US20200399228A1

  公开（公告）日：2020-12-24

  Disclosed is a compound of formula (I) in which R1, R2, and R3 are as described herein. Also provided are pharmaceutical compositions comprising the compound of formula (I) and methods of using the compound of formula (I), including a method of treating a disease or disorder and a method for effectuating a G-protein coupled receptor (GPCR)-mediated response in a subject.
• US8394790B2
  申请人：——

  公开号：US8394790B2

  公开（公告）日：2013-03-12
• US8828993B2
  申请人：——

  公开号：US8828993B2

  公开（公告）日：2014-09-09
• The First Structure–Activity Relationship Studies for Designer Receptors Exclusively Activated by Designer Drugs
  作者：Xin Chen、Hyunah Choo、Xi-Ping Huang、Xiaobao Yang、Orrin Stone、Bryan L. Roth、Jian Jin

  DOI：10.1021/cn500325v

  日期：2015.3.18

  Over the past decade, two independent technologies have emerged and been widely adopted by the neuroscience community for remotely controlling neuronal activity: optogenetics which utilize engineered channelrhodopsin and other opsins, and chemogenetics which utilize engineered G protein-coupled receptors (Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)) and other orthologous ligand receptor pairs. Using directed molecular evolution, two types of DREADDs derived from human muscarinic acetylcholine receptors have been developed: hM3Dq which activates neuronal firing, and hM4Di which inhibits neuronal firing. Importantly, these DREADDs were not activated by the native ligand acetylcholine (ACh), but selectively activated by dozapine N-oxide (CNO), a pharmacologically inert ligand. CNO has been used extensively in rodent models to activate DREADDs, and although CNO is not subject to significant metabolic transformation in mice, a small fraction of CNO is apparently metabolized to clozapine in humans and guinea pigs, lessening the translational potential of DREADDs. To effectively translate the DREADD technology, the next generation of DREADD agonists are needed and a thorough understanding of structure activity relationships (SARs) of DREADDs is required for developing such ligands. We therefore conducted the first SAR studies of hM3Dq. We explored multiple regions of the scaffold represented by CNO, identified interesting SAR trends, and discovered several compounds that are very potent hM3Dq agonists but do not activate the native human M3 receptor (hM3). We also discovered that the approved drug perlapine is a novel hM3Dq agonist with >10 000-fold selectivity for hM3Dq over hM3.