2-(2-(4-(4-(trifluoromethyl)benzoyl)thiazol-5-yl)ethyl)isoindoline-1,3-dione | 1357261-06-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(2-(4-(4-(trifluoromethyl)benzoyl)thiazol-5-yl)ethyl)isoindoline-1,3-dione
• 英文别名: 2-[2-[4-[4-(Trifluoromethyl)benzoyl]-1,3-thiazol-5-yl]ethyl]isoindole-1,3-dione
• CAS: 1357261-06-3
• 化学式: C₂₁H₁₃F₃N₂O₃S
• 分子量: 430.407
• InChiKey: IOMPHLAWGOZIMM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  95.6
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-(2-(4-(4-(trifluoromethyl)benzoyl)thiazol-5-yl)ethyl)isoindoline-1,3-dione 在 sodium tetrahydroborate 、 肼 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 72.5h， 生成 4-(4-(trifluoromethyl)phenyl)-4,5,6,7-tetrahydrothiazolo[4,5-c]-pyridine
  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 manganese(IV) oxide 、 tris-(dibenzylideneacetone)dipalladium(0) 、 palladium 10% on activated carbon 、 氢气 、 三乙胺 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 80.0 ℃ 、101.33 kPa 条件下， 反应 34.5h， 生成 2-(2-(4-(4-(trifluoromethyl)benzoyl)thiazol-5-yl)ethyl)isoindoline-1,3-dione
  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).