(1R,2R)-2-methyl-cyclopropanecarboxylic acid (4-acetyl-3-bromoisothiazol-5-yl)-amide | 1189746-31-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (1R,2R)-2-methyl-cyclopropanecarboxylic acid (4-acetyl-3-bromoisothiazol-5-yl)-amide
• 英文别名: (1R,2R)-N-(4-acetyl-3-bromo-1,2-thiazol-5-yl)-2-methylcyclopropane-1-carboxamide
• CAS: 1189746-31-3
• 化学式: C₁₀H₁₁BrN₂O₂S
• 分子量: 303.18
• InChiKey: ADTKCFYOCWVRKM-INEUFUBQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  87.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  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)-2-methyl-cyclopropanecarboxylic acid [3-(2-methyl-2H-indazol-5-yl)-4-pyridin-2-yl-isothiazol-5-yl]-amide hydrochloride
  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
• 作为产物：
  描述：

  2-氰基-3-氧代丁烷硫代酰胺 在 溴 、 三乙胺 作用下， 以 二氯甲烷 、 溶剂黄146 为溶剂， 生成 (1R,2R)-2-methyl-cyclopropanecarboxylic acid (4-acetyl-3-bromoisothiazol-5-yl)-amide
  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

文献信息

• 3-INDAZOLYL-4-PYRIDYLISOTHIAZOLES
  申请人：Britton Thomas Charles

  公开号：US20090253750A1

  公开（公告）日：2009-10-08

  The present invention provides 3-indazoyl-4-pyridylisothiazoles or a pharmaceutically acceptable salt thereof, pharmaceutical compositions thereof, and methods of using the same, as well as processes for preparing the same, and intermediates thereof.

  本发明提供3-吲哚基-4-吡啶基异噻唑或其药用可接受的盐，以及其药物组合物，并使用方法，以及制备方法和中间体。
• 3-indazolyl-4-pyridylisothiazoles
  申请人：Eli Lilly and Company

  公开号：US07932274B2

  公开（公告）日：2011-04-26

  The present invention provides 3-indazoyl-4-pyridylisothiazoles or a pharmaceutically acceptable salt thereof, pharmaceutical compositions thereof, and methods of using the same, as well as processes for preparing the same, and intermediates thereof.

  本发明提供3-吲唑基-4-吡啶基异噻唑烷或其药学上可接受的盐、其制药组合物、使用方法以及制备方法和中间体。
• US7932274B2
  申请人：——

  公开号：US7932274B2

  公开（公告）日：2011-04-26