(1R,2R)-N-[4-[6-(difluoromethyl)pyridin-2-yl]-3-(2-methylindazol-5-yl)-1,2-thiazol-5-yl]-2-methylcyclopropane-1-carboxamide | 1189806-55-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: (1R,2R)-N-[4-[6-(difluoromethyl)pyridin-2-yl]-3-(2-methylindazol-5-yl)-1,2-thiazol-5-yl]-2-methylcyclopropane-1-carboxamide
• CAS: 1189806-55-0
• 化学式: C₂₂H₁₉F₂N₅OS
• 分子量: 439.489
• InChiKey: LKDNBDVNZXUBSU-BXUZGUMPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (1R,2R)-2-methyl-cyclopropanecarboxylic acid (4-acetyl-3-bromoisothiazol-5-yl)-amide 在 bis-triphenylphosphine-palladium(II) chloride 、 二(三叔丁基膦)钯 、 溴 、 sodium carbonate 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 乙二醇二甲醚 、 水 为溶剂， 生成 (1R,2R)-N-[4-[6-(difluoromethyl)pyridin-2-yl]-3-(2-methylindazol-5-yl)-1,2-thiazol-5-yl]-2-methylcyclopropane-1-carboxamide
  参考文献：
  名称：

  Discovery of (1R,2R)-N-(4-(6-isopropylpyridin-2-yl)-3-(2-methyl-2H-indazol-5-yl)isothiazol-5-yl)-2-methylcyclopropanecarboxamide, a potent and orally efficacious mGlu5 receptor negative allosteric modulator

  摘要：

  A novel series of selective negative allosteric modulators (NAMs) for metabotropic glutamate receptor 5 (mGlu5) was discovered from an isothiazole scaffold. One compound of this series, (1R,2R)-N-(4-(6-isopropylpyridin-2-yl)-3-(2-methyl-2H-indazol-5-yl)isothiazol-5-yl)-2-methylcyclopropanecarboxamide (24), demonstrated satisfactory pharmacokinetic properties and, following oral dosing in rats, produced dose-dependent and long-lasting mGlu5 receptor occupancy. Consistent with the hypothesis that blockade of mGlu5 receptors will produce analgesic effects in mammals, compound 24 produced a dose-dependent reduction in paw licking responses in the formalin model of persistent pain. (c) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.01.009