5-chloro-N-(1,3,6,6-tetrafluoro-5-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-indole-2-carboxamide | 721446-42-0

• 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-chloro-N-(1,3,6,6-tetrafluoro-5-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-indole-2-carboxamide
• 英文别名: Indole-2-carboxamide derivative, 25e；5-chloro-N-(1,3,6,6-tetrafluoro-5-hydroxy-7,8-dihydro-5H-naphthalen-2-yl)-1H-indole-2-carboxamide
• CAS: 721446-42-0
• 化学式: C₁₉H₁₃ClF₄N₂O₂
• 分子量: 412.771
• InChiKey: NUFIIKLVNAEDGC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  65.1
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-chloro-N-(1,3,6,6-tetrafluoro-5-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-indole-2-carboxamide 、 N-对甲苯磺酰基-L-苯丙氨酰氯 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 28.5h， 以38%的产率得到6-(5-chloro-1H-indole-2-carboxamido)-2,2,5,7-tetrafluoro-1,2,3,4-tetrahydronaphthalen-1-yl tosyl-L-phenylalaninate
  参考文献：
  名称：

  Design, synthesis, and pharmacological evaluation of N-bicyclo-5-chloro-1H-indole-2-carboxamide derivatives as potent glycogen phosphorylase inhibitors

  摘要：

  As a result of the various N-bicyclo-5-chloro-1H-indole-2-carboxamide derivatives with a hydroxy moiety synthesized in an effort to discover novel glycogen phosphorylase (GP) inhibitors, 5-chloro-N-(5-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-indole-2-carboxamide (5b) was found to have potent inhibitory activity. The introduction of fluorine atoms both at a position adjacent to the hydroxy group and in the central benzene moiety lead to the optically active derivative 5-chloro-N-[(5R)-1,3,6,6-tetrafluoro-5-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1H-indole-2-carboxamide(25e alpha, which was the most potent compound in this series (IC(50) = 0.020 mu M). This compound inhibited glucagon-induced glucose output in cultured primary hepatocytes with an IC(50) value of 0.69 mu M, and showed oral hypoglycemic activity in diabetic db/db mice at 10 mg/kg. Compound 25e alpha also had an excellent pharmacokinetic profile, with high oral bioavailability and a long plasma half-life, in male SD rats. The binding mode of 25e alpha to this molecule and the role of fluorine atoms in that binding were speculated in an enzyme docking study. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.10.021
• 作为产物：
  描述：

  6-amino-2,2,5,7-tetrafluoro-1,2,3,4-tetrahydronaphthalen-1-ol 、 5-氯吲哚-2-羧酸氯 在 吡啶 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 12.5h， 以76%的产率得到5-chloro-N-(1,3,6,6-tetrafluoro-5-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-indole-2-carboxamide
  参考文献：
  名称：

  Design, synthesis, and pharmacological evaluation of N-bicyclo-5-chloro-1H-indole-2-carboxamide derivatives as potent glycogen phosphorylase inhibitors

  摘要：

  As a result of the various N-bicyclo-5-chloro-1H-indole-2-carboxamide derivatives with a hydroxy moiety synthesized in an effort to discover novel glycogen phosphorylase (GP) inhibitors, 5-chloro-N-(5-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-indole-2-carboxamide (5b) was found to have potent inhibitory activity. The introduction of fluorine atoms both at a position adjacent to the hydroxy group and in the central benzene moiety lead to the optically active derivative 5-chloro-N-[(5R)-1,3,6,6-tetrafluoro-5-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1H-indole-2-carboxamide(25e alpha, which was the most potent compound in this series (IC(50) = 0.020 mu M). This compound inhibited glucagon-induced glucose output in cultured primary hepatocytes with an IC(50) value of 0.69 mu M, and showed oral hypoglycemic activity in diabetic db/db mice at 10 mg/kg. Compound 25e alpha also had an excellent pharmacokinetic profile, with high oral bioavailability and a long plasma half-life, in male SD rats. The binding mode of 25e alpha to this molecule and the role of fluorine atoms in that binding were speculated in an enzyme docking study. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.10.021

文献信息

• Design, synthesis, and pharmacological evaluation of N-bicyclo-5-chloro-1H-indole-2-carboxamide derivatives as potent glycogen phosphorylase inhibitors
  作者：Kenichi Onda、Ryota Shiraki、Takashi Ogiyama、Kazuhiro Yokoyama、Kazuhiro Momose、Naoko Katayama、Masaya Orita、Tomohiko Yamaguchi、Masako Furutani、Noritaka Hamada、Makoto Takeuchi、Minoru Okada、Mitsuaki Ohta、Shin-ichi Tsukamoto

  DOI：10.1016/j.bmc.2008.10.021

  日期：2008.12

  As a result of the various N-bicyclo-5-chloro-1H-indole-2-carboxamide derivatives with a hydroxy moiety synthesized in an effort to discover novel glycogen phosphorylase (GP) inhibitors, 5-chloro-N-(5-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-indole-2-carboxamide (5b) was found to have potent inhibitory activity. The introduction of fluorine atoms both at a position adjacent to the hydroxy group and in the central benzene moiety lead to the optically active derivative 5-chloro-N-[(5R)-1,3,6,6-tetrafluoro-5-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1H-indole-2-carboxamide(25e alpha, which was the most potent compound in this series (IC(50) = 0.020 mu M). This compound inhibited glucagon-induced glucose output in cultured primary hepatocytes with an IC(50) value of 0.69 mu M, and showed oral hypoglycemic activity in diabetic db/db mice at 10 mg/kg. Compound 25e alpha also had an excellent pharmacokinetic profile, with high oral bioavailability and a long plasma half-life, in male SD rats. The binding mode of 25e alpha to this molecule and the role of fluorine atoms in that binding were speculated in an enzyme docking study. (c) 2008 Elsevier Ltd. All rights reserved.