2-[6-Bromo-2,4-dioxo-1-(2-phenylethyl)quinazolin-3-yl]acetic acid | 133166-68-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2-[6-Bromo-2,4-dioxo-1-(2-phenylethyl)quinazolin-3-yl]acetic acid
• CAS: 133166-68-4
• 化学式: C₁₈H₁₅BrN₂O₄
• 分子量: 403.232
• InChiKey: IQBYRNZWJBZBCU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  77.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-溴靛红酸酐 在 sodium hydroxide 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 反应 18.5h， 生成 2-[6-Bromo-2,4-dioxo-1-(2-phenylethyl)quinazolin-3-yl]acetic acid
  参考文献：
  名称：

  Quinazolineacetic acids and related analogs as aldose reductase inhibitors

  摘要：

  A variety of 2,4-dioxoquinazolineacetic acids (10, 11) were synthesized as hybrids of the known aldose reductase inhibitors alrestatin (8), ICI-105,552 (9), and ICI-128,436 (2) and evaluated for their ability to inhibit partially purified bovine lens aldose reductase (in vitro) and their effectiveness to decrease galactitol accumulation in the 4-day galactosemic rat model (in vivo). In support to SAR studies, related analogues pyrimidinediones (12), dihydroquinazolones (13), and indazolidinones (14, 15) were synthesized and tested in the in vitro and in vivo assays. All prepared compounds (10-15) have shown a high level of in vitro activity (IC50 approximately 10(-6) to 4 x 10(-8) M). However, only the 2,4-quinazolinedione analogues 10 and 11, with similar N-aralkyl substitution found in 2 and 9, have exhibited good oral potency. The remaining compounds were either inactive or had only a marginal in vivo activity. The structure-activity data support the presence of a secondary hydrophobic pocket in the vicinity of the primary lipophilic region of the enzyme.

  DOI：

  10.1021/jm00108a038

文献信息

• [EN] ACC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE L'ACC ET UTILISATIONS ASSOCIÉES
  申请人：NIMBUS APOLLO INC

  公开号：WO2014182951A1

  公开（公告）日：2014-11-13

  The present invention provides for compounds of formula I as acetyl-CoA carboxylase (ACC) inhibitors. The ACC inhibitors are useful for the prevention or treatment of metabolic syndrome, including obesity, dyslipidemia and hyperlipidemia in humans. The inhibitor compounds are also capable of inhibiting the ACC enzyme found in plants, parasites and bacteria.

  本发明提供了I式化合物作为乙酰辅酶A羧化酶(ACC)抑制剂。该ACC抑制剂可用于预防或治疗人类代谢综合征，包括肥胖症、血脂异常和高脂血症。该抑制剂化合物还能够抑制植物、寄生虫和细菌中发现的ACC酶。
• ACC INHIBITORS AND USES THEREOF
  申请人：Nimbus Apollo, Inc.

  公开号：US20160185783A1

  公开（公告）日：2016-06-30

  The present invention provides for compounds of formula I as acetyl-CoA carboxylase (ACC) inhibitors. The ACC inhibitors are useful for the prevention or treatment of metabolic syndrome, including obesity, dyslipidemia and hyperlipidemia in humans. The inhibitor compounds are also capable of inhibiting the ACC enzyme found in plants, parasites and bacteria.
• Quinazolineacetic acids and related analogs as aldose reductase inhibitors
  作者：Michael S. Malamas、Jane Millen

  DOI：10.1021/jm00108a038

  日期：1991.4

  A variety of 2,4-dioxoquinazolineacetic acids (10, 11) were synthesized as hybrids of the known aldose reductase inhibitors alrestatin (8), ICI-105,552 (9), and ICI-128,436 (2) and evaluated for their ability to inhibit partially purified bovine lens aldose reductase (in vitro) and their effectiveness to decrease galactitol accumulation in the 4-day galactosemic rat model (in vivo). In support to SAR studies, related analogues pyrimidinediones (12), dihydroquinazolones (13), and indazolidinones (14, 15) were synthesized and tested in the in vitro and in vivo assays. All prepared compounds (10-15) have shown a high level of in vitro activity (IC50 approximately 10(-6) to 4 x 10(-8) M). However, only the 2,4-quinazolinedione analogues 10 and 11, with similar N-aralkyl substitution found in 2 and 9, have exhibited good oral potency. The remaining compounds were either inactive or had only a marginal in vivo activity. The structure-activity data support the presence of a secondary hydrophobic pocket in the vicinity of the primary lipophilic region of the enzyme.