(3aS,7aR)-3a-(3,4-dichlorophenyl)-2-methyloctahydro-1H-isoindole | 1233387-92-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (3aS,7aR)-3a-(3,4-dichlorophenyl)-2-methyloctahydro-1H-isoindole
• 英文别名: (3aR,7aS)-7a-(3,4-dichlorophenyl)-2-methyl-3,3a,4,5,6,7-hexahydro-1H-isoindole
• CAS: 1233387-92-2
• 化学式: C₁₅H₁₉Cl₂N
• 分子量: 284.229
• InChiKey: FEYNATNTSNGKKO-SWLSCSKDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  3,4-二氯溴苯 在 正丁基锂 、 三叔丁基膦 、 甲基磺酰氯 、 lithium hexamethyldisilazane 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正己烷 、 二乙胺 、 甲苯 为溶剂， 反应 0.33h， 生成 (3aS,7aR)-3a-(3,4-dichlorophenyl)-2-methyloctahydro-1H-isoindole
  参考文献：
  名称：

  Synthesis and Pharmacological Characterization of Bicyclic Triple Reuptake Inhibitor 3-Aryl Octahydrocyclopenta[c]pyrrole Analogues

  摘要：

  The present work expands the chemical space known to offer potent inhibition of the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT) and discloses novel bicyclic octahydrocyclopenta[c]pyrrole and octahydro-1H-isoindole scaffolds as potent triple reuptake inhibitors (TRIs) for the potential treatment of depression. Optimized compounds 22a (SEAT, NET, DAT, IC(50) = 20, 109, 430 nM), 23a (SERT, NET, DAT, IC(50) = 29, 85, 168 nM), and 26a (SERT, NET, DAT, IC(50) = 53, 150, 140 nM) were highly brain penetrant, active in vivo in the mouse tail suspension test at 10 and 30 mpk PO, and were not generally motor stimulants at doses ranging from 1 to 30 mpk PO. Moderate in vitro cytochrome P450 (CYP) and potassium ion channel Kv11.1 (hERG) inhibition were uncovered as potential liabilities for the chemical series.

  DOI：

  10.1021/jm101312a

文献信息

• [EN] TRIPLE REUPTAKE INHIBITORS AND METHODS OF THEIR USE<br/>[FR] INHIBITEURS DE TRIPLE RECAPTURE ET LEURS MÉTHODES D'UTILISATION
  申请人：SEPRACOR INC

  公开号：WO2010075064A1

  公开（公告）日：2010-07-01

  Provided herein are bicyclic compounds and methods of synthesis thereof. The compounds provided herein are useful for the treatment, prevention, and/or management of various neurological disorders. Compounds provided herein inhibit reuptake of endogenous monoamines, such as dopamine, serotonin and norepinephrine (e.g., from the synaptic cleft) and modulate one or more monoamine transporter. Pharmaceutical formulations containing the compounds are also provided.

  本文提供了双环化合物及其合成方法。本文提供的化合物可用于治疗、预防和/或管理各种神经系统疾病。本文提供的化合物抑制内源单胺的再摄取，如多巴胺、5-羟色胺和去甲肾上腺素（例如，从突触缝中），并调节一个或多个单胺转运体。还提供了含有这些化合物的药物配方。
• TRIPLE REUPTAKE INHIBITORS AND METHODS OF THEIR USE
  申请人：Shao Liming

  公开号：US20110313013A1

  公开（公告）日：2011-12-22

  Provided herein are bicyclic compounds and methods of synthesis thereof. The compounds provided herein are useful for the treatment, prevention, and/or management of various neurological disorders. Compounds provided herein inhibit uptake of endogenous monoamines, such as dopamine, serotonin and norepinephrine (e.g., from the synaptic cleft) and modulate one or more monoamine transporter. Pharmaceutical formulations containing the compounds are also provided.

  本文提供了双环化合物及其合成方法。这些化合物对于治疗、预防和/或管理各种神经系统疾病非常有用。所提供的化合物抑制内源性单胺的摄取，如多巴胺、血清素和去甲肾上腺素（例如从突触间隙）并调节一个或多个单胺转运体。还提供了含有这些化合物的制药配方。
• Triple reuptake inhibitors and methods of their use
  申请人：SUNOVION PHARMACEUTICALS INC.

  公开号：US10428021B2

  公开（公告）日：2019-10-01

  Provided herein are bicyclic compounds and methods of synthesis thereof. The compounds provided herein are useful for the treatment, prevention, and/or management of various neurological disorders. Compounds provided herein inhibit reuptake of endogenous monoamines, such as dopamine, serotonin and norepinephrine (e.g., from the synaptic cleft) and modulate one or more monoamine transporter. Pharmaceutical formulations containing the compounds are also provided.

  本文提供的是双环化合物及其合成方法。本文提供的化合物可用于治疗、预防和/或控制各种神经系统疾病。本文提供的化合物可抑制多巴胺、5-羟色胺和去甲肾上腺素等内源性单胺的再摄取（如从突触间隙），并调节一种或多种单胺转运体。还提供了含有这些化合物的药物制剂。
• US8592608B2
  申请人：——

  公开号：US8592608B2

  公开（公告）日：2013-11-26
• US9133117B2
  申请人：——

  公开号：US9133117B2

  公开（公告）日：2015-09-15