6-amino-7-methoxy-3,4-dihydronaphthalen-1(2H)-one | 1099766-64-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 6-amino-7-methoxy-3,4-dihydronaphthalen-1(2H)-one
• 英文别名: 6-Amino-7-methoxy-1-tetralone；6-amino-7-methoxy-3,4-dihydro-2H-naphthalen-1-one
• CAS: 1099766-64-9
• 化学式: C₁₁H₁₃NO₂
• 分子量: 191.23
• InChiKey: XLLRVPFYLKYEAE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-amino-7-methoxy-3,4-dihydronaphthalen-1(2H)-one 、 三氟乙酸酐 以 氯仿 为溶剂， 反应 1.0h， 以92%的产率得到2,2,2-trifluoro-N-(3-methoxy-5-oxo-5,6,7,8-tetrahydronaphthalen-2-yl)acetamide
  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：

  7-Methoxy-6-nitro-1-tetralone 在 10% Pd/C 、 氢气 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以90%的产率得到6-amino-7-methoxy-3,4-dihydronaphthalen-1(2H)-one
  参考文献：
  名称：

  Conformationally constrained analogues of N′-(4-tert-butylbenzyl)-N-(4-methylsulfonylaminobenzyl)thiourea as TRPV1 antagonists

  摘要：

  A series of bicyclic analogues having indan and tetrahydronaphthalene templates in the A-region were designed as conformationally constrained analogues of our previously reported potent TRPV1 antagonists (1, 3). The activities for rat TRPV1 of the conformationally restricted analogues were moderately or markedly diminished, particularly in the case of the tetrahydronaphthalene analogues. The analysis indicated that steric constraints at the benzylic position in the bicyclic analogues may be an important factor for their unfavorable interaction with the receptor. (C) 2008 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2008.02.026

文献信息

• INDENONCARBOXYLIC ACIDS DERIVATIVES AND THEIR USE FOR THE TREATMENT OF AND PREVENTING DIABETES AND DYSLIPIDAEMIA
  申请人：Merck Patent GmbH

  公开号：EP1583738B1

  公开（公告）日：2017-05-10
• Conformationally constrained analogues of N′-(4-tert-butylbenzyl)-N-(4-methylsulfonylaminobenzyl)thiourea as TRPV1 antagonists
  作者：Ju-Ok Lim、Mi-Kyoung Jin、HyungChul Ryu、Dong Wook Kang、Jeewoo Lee、Larry V. Pearce、Richard Tran、Attila Toth、Peter M. Blumberg

  DOI：10.1016/j.ejmech.2008.02.026

  日期：2009.1

  A series of bicyclic analogues having indan and tetrahydronaphthalene templates in the A-region were designed as conformationally constrained analogues of our previously reported potent TRPV1 antagonists (1, 3). The activities for rat TRPV1 of the conformationally restricted analogues were moderately or markedly diminished, particularly in the case of the tetrahydronaphthalene analogues. The analysis indicated that steric constraints at the benzylic position in the bicyclic analogues may be an important factor for their unfavorable interaction with the receptor. (C) 2008 Elsevier Masson SAS. All rights reserved.
• 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.