1-(4-(trifluoromethyl)phenyl)isoindoline | 1357261-48-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(4-(trifluoromethyl)phenyl)isoindoline
• 英文别名: 1-[4-(trifluoromethyl)phenyl]-2,3-dihydro-1H-isoindole
• CAS: 1357261-48-3
• 化学式: C₁₅H₁₂F₃N
• 分子量: 263.262
• InChiKey: JZIDWRDOARPGIQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(4-(trifluoromethyl)phenyl)isoindoline 、 异氰酸对氟苯基酯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以41%的产率得到N-(4-fluorophenyl)-1-(4-(trifluoromethyl)phenyl)isoindoline-2-carboxamide
  参考文献：
  名称：

  Fused Piperidines as a Novel Class of Potent and Orally Available Transient Receptor Potential Melastatin Type 8 (TRPM8) Antagonists

  摘要：

  The transient receptor potential melastatin type 8 (TRPM8) is a nonselective cation channel primarily expressed in a subpopulation of sensory neurons that can be activated by a wide range of stimuli, including menthol, icilin, and cold temperatures (< 25 degrees C). Antagonism of TRPM8 is currently under investigation as a new approach for the treatment of pain. As a result of our screening efforts, we identified tetrahydrothienopyridine 4 as an inhibitor of icilin-induced calcium influx in CHO cells expressing recombinant rat TRPM8. Exploration of the structure-activity relationships of 4 led to the identification of a potent and orally bioavailable TRPM8 antagonist, tetrahydroisoquinoline 87. Compound 87 demonstrated target coverage in vivo after oral administration in a rat pharmacodynamic model measuring the prevention of icilin-induced wet-dog shakes (WDS).

  DOI：

  10.1021/jm2013634
• 作为产物：
  描述：

  4-三氟甲基苯基溴化镁 在 三乙基硅烷 、 N,N-二甲基丙烯基脲 、 lithium aluminium tetrahydride 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 20.08h， 生成 1-(4-(trifluoromethyl)phenyl)isoindoline
  参考文献：
  名称：

  Fused Piperidines as a Novel Class of Potent and Orally Available Transient Receptor Potential Melastatin Type 8 (TRPM8) Antagonists

  摘要：

  The transient receptor potential melastatin type 8 (TRPM8) is a nonselective cation channel primarily expressed in a subpopulation of sensory neurons that can be activated by a wide range of stimuli, including menthol, icilin, and cold temperatures (< 25 degrees C). Antagonism of TRPM8 is currently under investigation as a new approach for the treatment of pain. As a result of our screening efforts, we identified tetrahydrothienopyridine 4 as an inhibitor of icilin-induced calcium influx in CHO cells expressing recombinant rat TRPM8. Exploration of the structure-activity relationships of 4 led to the identification of a potent and orally bioavailable TRPM8 antagonist, tetrahydroisoquinoline 87. Compound 87 demonstrated target coverage in vivo after oral administration in a rat pharmacodynamic model measuring the prevention of icilin-induced wet-dog shakes (WDS).

  DOI：

  10.1021/jm2013634

文献信息

• Fused Piperidines as a Novel Class of Potent and Orally Available Transient Receptor Potential Melastatin Type 8 (TRPM8) Antagonists
  作者：Nuria A. Tamayo、Yunxin Bo、Vijay Gore、Vu Ma、Nobuko Nishimura、Phi Tang、Hong Deng、Lana Klionsky、Sonya G. Lehto、Weiya Wang、Brad Youngblood、Jiyun Chen、Tiffany L. Correll、Michael D. Bartberger、Narender R. Gavva、Mark H. Norman

  DOI：10.1021/jm2013634

  日期：2012.2.23

  The transient receptor potential melastatin type 8 (TRPM8) is a nonselective cation channel primarily expressed in a subpopulation of sensory neurons that can be activated by a wide range of stimuli, including menthol, icilin, and cold temperatures (< 25 degrees C). Antagonism of TRPM8 is currently under investigation as a new approach for the treatment of pain. As a result of our screening efforts, we identified tetrahydrothienopyridine 4 as an inhibitor of icilin-induced calcium influx in CHO cells expressing recombinant rat TRPM8. Exploration of the structure-activity relationships of 4 led to the identification of a potent and orally bioavailable TRPM8 antagonist, tetrahydroisoquinoline 87. Compound 87 demonstrated target coverage in vivo after oral administration in a rat pharmacodynamic model measuring the prevention of icilin-induced wet-dog shakes (WDS).