1-甲基-(1,2,3,4-四氢喹啉-6-基)氨基甲酸叔丁酯 | 1007197-95-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 1-甲基-(1,2,3,4-四氢喹啉-6-基)氨基甲酸叔丁酯
• 英文名称: 1-methyl-(1,2,3,4-tetrahydroquinolin-6-yl)carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-(1-methyl-3,4-dihydro-2H-quinolin-6-yl)carbamate
• CAS: 1007197-95-6
• 化学式: C₁₅H₂₂N₂O₂
• 分子量: 262.352
• InChiKey: WEVJQELEBLCJTN-UHFFFAOYSA-N

物化性质

• 沸点：
  361.1±35.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-甲基-(1,2,3,4-四氢喹啉-6-基)氨基甲酸叔丁酯 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以80%的产率得到1-methyl-1,2,3,4-tetrahydroquinolin-6-ylamine
  参考文献：
  名称：

  Discovery and Biological Evaluation of 5-Aryl-2-furfuramides, Potent and Selective Blockers of the Na_v1.8 Sodium Channel with Efficacy in Models of Neuropathic and Inflammatory Pain

  摘要：

  Na(v)1.8 (also known as PN3) is a tetrodotoxin-resistant (TTx-r) voltage-gated sodium channel (VGSC) that is highly expressed on small diameter sensory neurons and has been implicated in the pathophysiology of inflammatory and neuropathic pain. Recent studies using an Na(v)1.8 antisense oligonucleotide in an animal model of chronic pain indicated that selective blockade of Na(v)1.8 was analgesic and could provide effective analgesia with a reduction in the adverse events associated with nonselective VGSC blocking therapeutic agents. Herein, we describe the preparation and characterization of a series of 5-substituted 2-furfuramides, which are potent, voltage-dependent blockers (IC50 < 10 nM) of the human Na(v)1.8 channel. Selected derivatives, such as 7 and 27, also blocked TTx-r sodium currents in rat dorsal root ganglia (DRG) neurons with comparable potency and displayed > 100-fold selectivity versus human sodium (Na(v)1.2, Na(v)1.5, Na(v)1.7) and human ether-a-go-go (hERG) channels. Following systemic administration, compounds 7 and dose-dependently reduced neuropathic and inflammatory pain in experimental rodent models.

  DOI：

  10.1021/jm070637u
• 作为产物：
  描述：

  聚合甲醛 、 1,2,3,4-四氢-6-喹啉基氨基甲酸叔丁酯 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 甲醇 、 水 为溶剂， 反应 4.0h， 以422 mg的产率得到1-甲基-(1,2,3,4-四氢喹啉-6-基)氨基甲酸叔丁酯
  参考文献：
  名称：

  Discovery and Biological Evaluation of 5-Aryl-2-furfuramides, Potent and Selective Blockers of the Na_v1.8 Sodium Channel with Efficacy in Models of Neuropathic and Inflammatory Pain

  摘要：

  Na(v)1.8 (also known as PN3) is a tetrodotoxin-resistant (TTx-r) voltage-gated sodium channel (VGSC) that is highly expressed on small diameter sensory neurons and has been implicated in the pathophysiology of inflammatory and neuropathic pain. Recent studies using an Na(v)1.8 antisense oligonucleotide in an animal model of chronic pain indicated that selective blockade of Na(v)1.8 was analgesic and could provide effective analgesia with a reduction in the adverse events associated with nonselective VGSC blocking therapeutic agents. Herein, we describe the preparation and characterization of a series of 5-substituted 2-furfuramides, which are potent, voltage-dependent blockers (IC50 < 10 nM) of the human Na(v)1.8 channel. Selected derivatives, such as 7 and 27, also blocked TTx-r sodium currents in rat dorsal root ganglia (DRG) neurons with comparable potency and displayed > 100-fold selectivity versus human sodium (Na(v)1.2, Na(v)1.5, Na(v)1.7) and human ether-a-go-go (hERG) channels. Following systemic administration, compounds 7 and dose-dependently reduced neuropathic and inflammatory pain in experimental rodent models.

  DOI：

  10.1021/jm070637u

文献信息

• Discovery and Biological Evaluation of 5-Aryl-2-furfuramides, Potent and Selective Blockers of the Na_v1.8 Sodium Channel with Efficacy in Models of Neuropathic and Inflammatory Pain
  作者：Michael E. Kort、Irene Drizin、Robert J. Gregg、Marc J. C. Scanio、Lei Shi、Michael F. Gross、Robert N. Atkinson、Matthew S. Johnson、Gregory J. Pacofsky、James B. Thomas、William A. Carroll、Michael J. Krambis、Dong Liu、Char-Chang Shieh、XuFeng Zhang、Gricelda Hernandez、Joseph P. Mikusa、Chengmin Zhong、Shailen Joshi、Prisca Honore、Rosemarie Roeloffs、Kennan C. Marsh、Bernard P. Murray、Jinrong Liu、Stephen Werness、Connie R. Faltynek、Douglas S. Krafte、Michael F. Jarvis、Mark L. Chapman、Brian E. Marron

  DOI：10.1021/jm070637u

  日期：2008.2.1

  Na(v)1.8 (also known as PN3) is a tetrodotoxin-resistant (TTx-r) voltage-gated sodium channel (VGSC) that is highly expressed on small diameter sensory neurons and has been implicated in the pathophysiology of inflammatory and neuropathic pain. Recent studies using an Na(v)1.8 antisense oligonucleotide in an animal model of chronic pain indicated that selective blockade of Na(v)1.8 was analgesic and could provide effective analgesia with a reduction in the adverse events associated with nonselective VGSC blocking therapeutic agents. Herein, we describe the preparation and characterization of a series of 5-substituted 2-furfuramides, which are potent, voltage-dependent blockers (IC50 < 10 nM) of the human Na(v)1.8 channel. Selected derivatives, such as 7 and 27, also blocked TTx-r sodium currents in rat dorsal root ganglia (DRG) neurons with comparable potency and displayed > 100-fold selectivity versus human sodium (Na(v)1.2, Na(v)1.5, Na(v)1.7) and human ether-a-go-go (hERG) channels. Following systemic administration, compounds 7 and dose-dependently reduced neuropathic and inflammatory pain in experimental rodent models.