6-bromo-2-ethyl-4H-benzo[d][1,3]oxazin-4-one | 68100-91-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 6-bromo-2-ethyl-4H-benzo[d][1,3]oxazin-4-one
• 英文别名: 6-bromo-2-ethyl-4H-3,1-benzoxazin-4-one；6-bromo-2-ethyl-benzo[d][1,3]oxazin-4-one；6-bromo-2-ethyl-3,1-benzoxazin-4-one
• CAS: 68100-91-4
• 化学式: C₁₀H₈BrNO₂
• 分子量: 254.083
• InChiKey: HLNCIHYOKRIBOW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  38.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-bromo-2-ethyl-4H-benzo[d][1,3]oxazin-4-one 在 sodium hydroxide 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 苯 为溶剂， 反应 11.0h， 生成 2-(6-Bromo-2-ethyl-4-oxoquinazolin-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
• 作为产物：
  描述：

  丙酸酐 、 2-氨基-5-溴苯甲酸 反应 2.0h， 生成 6-bromo-2-ethyl-4H-benzo[d][1,3]oxazin-4-one
  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

• Design, synthesis, molecular modeling and anti-hyperglycemic evaluation of quinazolin-4(3H)-one derivatives as potential PPARγ and SUR agonists
  作者：Mohamed K. Ibrahim、Ibrahim H. Eissa、Mohamed S. Alesawy、Ahmed M. Metwaly、Mohamed M. Radwan、Mahmoud A. ElSohly

  DOI：10.1016/j.bmc.2017.07.015

  日期：2017.9

  Peroxisome proliferator-activated receptor gamma (PPARγ) and sulfonylurea receptor (SUR) play crucial roles in management of type-2 diabetes mellitus. In this study, a series of novel quinazoline-4(3H)-one-sulfonylurea hybrids were designed and synthesized as dual PPARγ and SUR agonists. The synthesized compounds were evaluated for their in vivo anti-hyperglycemic activities against STZ-induced hyperglycemic

  过氧化物酶体增殖物激活受体γ（PPARγ）和磺酰脲受体（SUR）在2型糖尿病的治疗中起着至关重要的作用。在这项研究中，设计并合成了一系列新颖的喹唑啉-4（3 H）-单磺酰脲杂化物，作为PPARγ和SUR双重激动剂。评价合成的化合物对STZ诱导的高血糖大鼠的体内抗高血糖活性。四种化合物（19一个，19 d，19 ˚F和25克）显示了强的活动，减少的40.43，46.42，41.23分别和42.50％，血糖水平。在体外进一步评估了活性最高的十种化合物其PPARγ结合亲和力和胰岛素分泌能力。化合物19 b，19 d，19 ˚F，25 ˚F和25克表现出对PPARγ最高的亲和力与IC 50个分别为0.371，0.350，0.369，0.408和0.353μM，值。另外，化合物19 d，19 ˚F，和25 d显示出与EC最高胰岛素分泌活动50值分别为0.97、1.01和1.15 µM。此外，进行了分
• Kumar, Atul; Singh, S.; Saxena, A. K., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1988, vol. 27, # 1-12, p. 443 - 447
  作者：Kumar, Atul、Singh, S.、Saxena, A. K.、Shanker, K.

  DOI：——

  日期：——
• El-Naser Ossman; El-Sayed Barakat, Arzneimittel-Forschung/Drug Research, 1994, vol. 44, # 8, p. 915 - 919
  作者：El-Naser Ossman、El-Sayed Barakat

  DOI：——

  日期：——
• Arora,R.C. et al., Journal of Heterocyclic Chemistry, 1978, vol. 15, p. 869 - 871
  作者：Arora,R.C. et al.

  DOI：——

  日期：——
• Dhatt; Bami, Journal Of Scientific and Industrial Research, 1959, vol. 18C, p. 256
  作者：Dhatt、Bami

  DOI：——

  日期：——