5-fluoro-3-[(naphthalen-1-yl)carbonyl]-1H-indole | 133437-49-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5-fluoro-3-[(naphthalen-1-yl)carbonyl]-1H-indole
• 英文别名: (5-fluoro-1H-indol-3-yl)-naphthalen-1-ylmethanone
• CAS: 133437-49-7
• 化学式: C₁₉H₁₂FNO
• 分子量: 289.309
• InChiKey: JIAARICWDZGSGJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.69
• 重原子数：
  22.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  32.86
• 氢给体数：
  1.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  1-溴戊烷 、 5-fluoro-3-[(naphthalen-1-yl)carbonyl]-1H-indole 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 0.58h， 以81%的产率得到5-fluoro-3-[(naphthalen-1-yl)carbonyl]-1-pentyl-1H-indole
  参考文献：
  名称：

  Peripherally Selective Cannabinoid 1 Receptor (CB1R) Agonists for the Treatment of Neuropathic Pain

  摘要：

  Alleviation of neuropathic pain by cannabinoids is limited by their central nervous system (CNS) side effects. Indole and indene compounds were engineered for high hCB1R affinity, peripheral selectivity, metabolic stability, and in vivo efficacy. An epithelial cell line assay identified candidates with blood brain barrier penetration for testing in a rat neuropathy induced by unilateral sciatic nerve entrapment (SNE). The SNE-induced mechanical allodynia was reversibly suppressed, partially or completely, after intraperitoneal or oral administration of several indenes. At doses-that relieve neuropathy symptoms, the indenes completely lacked, while the brain-permeant CB1R agonist HU-210 (1) exhibited strong CNS side effects, in catalepsy, hypothermia, and motor incoordination assays. Pharmacokinetic findings of similar to 0.001 cerebrospinal fluid:plasma ratio further supported limited CNS penetration. Pretreatment with selective CB1R or CB2R blockers suggested mainly CB1R contribution to an indene's antiallodynic effects. Therefore, this class of CB1R agonists holds promise as a viable treatment for neuropathic pain.

  DOI：

  10.1021/acs.jmedchem.6b00516
• 作为产物：
  描述：

  5-氟吲哚 、 1-萘甲酰氯 在 甲基溴化镁 、 zinc(II) chloride 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 以85%的产率得到5-fluoro-3-[(naphthalen-1-yl)carbonyl]-1H-indole
  参考文献：
  名称：

  Peripherally Selective Cannabinoid 1 Receptor (CB1R) Agonists for the Treatment of Neuropathic Pain

  摘要：

  Alleviation of neuropathic pain by cannabinoids is limited by their central nervous system (CNS) side effects. Indole and indene compounds were engineered for high hCB1R affinity, peripheral selectivity, metabolic stability, and in vivo efficacy. An epithelial cell line assay identified candidates with blood brain barrier penetration for testing in a rat neuropathy induced by unilateral sciatic nerve entrapment (SNE). The SNE-induced mechanical allodynia was reversibly suppressed, partially or completely, after intraperitoneal or oral administration of several indenes. At doses-that relieve neuropathy symptoms, the indenes completely lacked, while the brain-permeant CB1R agonist HU-210 (1) exhibited strong CNS side effects, in catalepsy, hypothermia, and motor incoordination assays. Pharmacokinetic findings of similar to 0.001 cerebrospinal fluid:plasma ratio further supported limited CNS penetration. Pretreatment with selective CB1R or CB2R blockers suggested mainly CB1R contribution to an indene's antiallodynic effects. Therefore, this class of CB1R agonists holds promise as a viable treatment for neuropathic pain.

  DOI：

  10.1021/acs.jmedchem.6b00516

文献信息

• Peripherally Selective Cannabinoid 1 Receptor (CB1R) Agonists for the Treatment of Neuropathic Pain
  作者：Herbert H. Seltzman、Craig Shiner、Erin E. Hirt、Anne F. Gilliam、Brian F. Thomas、Rangan Maitra、Rod Snyder、Sherry L. Black、Purvi R. Patel、Yatendra Mulpuri、Igor Spigelman

  DOI：10.1021/acs.jmedchem.6b00516

  日期：2016.8.25

  Alleviation of neuropathic pain by cannabinoids is limited by their central nervous system (CNS) side effects. Indole and indene compounds were engineered for high hCB1R affinity, peripheral selectivity, metabolic stability, and in vivo efficacy. An epithelial cell line assay identified candidates with blood brain barrier penetration for testing in a rat neuropathy induced by unilateral sciatic nerve entrapment (SNE). The SNE-induced mechanical allodynia was reversibly suppressed, partially or completely, after intraperitoneal or oral administration of several indenes. At doses-that relieve neuropathy symptoms, the indenes completely lacked, while the brain-permeant CB1R agonist HU-210 (1) exhibited strong CNS side effects, in catalepsy, hypothermia, and motor incoordination assays. Pharmacokinetic findings of similar to 0.001 cerebrospinal fluid:plasma ratio further supported limited CNS penetration. Pretreatment with selective CB1R or CB2R blockers suggested mainly CB1R contribution to an indene's antiallodynic effects. Therefore, this class of CB1R agonists holds promise as a viable treatment for neuropathic pain.