(3aS,7aR)-2-methyl-7a-naphthalen-2-yl-3,3a,4,5,6,7-hexahydro-1H-isoindole | 1314593-96-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (3aS,7aR)-2-methyl-7a-naphthalen-2-yl-3,3a,4,5,6,7-hexahydro-1H-isoindole
• CAS: 1314593-96-8
• 化学式: C₁₉H₂₃N
• 分子量: 265.398
• InChiKey: BIDMNSYJUSJTRE-MOPGFXCFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (3aS,7aR)-2-methyl-7a-naphthalen-2-yl-3,3a,4,5,6,7-hexahydro-1H-isoindole 在 ChiralTech AD column 作用下， 以 甲醇 、 乙醇 、 正己烷 、 二乙胺 为溶剂， 生成 、
  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
• 作为产物：
  描述：

  8-oxabicyclo[4,3,0]nonane-7-one 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)-2-methyl-7a-naphthalen-2-yl-3,3a,4,5,6,7-hexahydro-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

• Synthesis and Pharmacological Characterization of Bicyclic Triple Reuptake Inhibitor 3-Aryl Octahydrocyclopenta[<i>c</i>]pyrrole Analogues
  作者：Liming Shao、Michael C. Hewitt、Scott C. Malcolm、Fengjiang Wang、Jianguo Ma、Una C. Campbell、Nancy A. Spicer、Sharon R. Engel、Larry W. Hardy、Zhi-Dong Jiang、Rudy Schreiber、Kerry L. Spear、Mark A. Varney

  DOI：10.1021/jm101312a

  日期：2011.8.11

  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.