6-bromo-2-isopropyl-4H-3,1-benzoxazin-4-one | 761458-01-9

• 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-isopropyl-4H-3,1-benzoxazin-4-one
• 英文别名: 6-bromo-2-propan-2-yl-3,1-benzoxazin-4-one
• CAS: 761458-01-9
• 化学式: C₁₁H₁₀BrNO₂
• 分子量: 268.11
• InChiKey: DAFCPCGFHGQBAM-UHFFFAOYSA-N

物化性质

• 沸点：
  364.3±44.0 °C(Predicted)
• 密度：
  1.55±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 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-isopropyl-4H-3,1-benzoxazin-4-one 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以70%的产率得到3-amino-6-bromo-2-isopropyl-4(3H)-quinazolin-4-one
  参考文献：
  名称：

  一锅合成一些动态的2-取代的苯并恶嗪酮及其相应的预期生物活性的喹唑啉酮

  摘要：

  6-溴-2-异丙基-4（3H）-3,1-苯并恶嗪-4-酮与单和二齿氮亲核试剂的反应，例如脂肪族和芳香族伯胺，1,2-苯二胺，水合肼，已经研究了甲酰胺和甲酰胺，并提供了相应的喹唑啉酮，预期它们具有一些有趣的生物学活性。研究了3，1-苯并恶嗪-4-酮在碱性介质中对活性亚甲基化合物即乙酰丙酮的行为，并得到了3-乙酰喹啉。最后的反应被认为是杂环转化反应的说明性模型。

  DOI：

  10.1002/jhet.2389
• 作为产物：
  描述：

  异丁酰氯 、 2-氨基-5-溴苯甲酸 在 吡啶 、 乙酸酐 作用下， 反应 3.0h， 生成 6-bromo-2-isopropyl-4H-3,1-benzoxazin-4-one
  参考文献：
  名称：

  一锅合成一些动态的2-取代的苯并恶嗪酮及其相应的预期生物活性的喹唑啉酮

  摘要：

  6-溴-2-异丙基-4（3H）-3,1-苯并恶嗪-4-酮与单和二齿氮亲核试剂的反应，例如脂肪族和芳香族伯胺，1,2-苯二胺，水合肼，已经研究了甲酰胺和甲酰胺，并提供了相应的喹唑啉酮，预期它们具有一些有趣的生物学活性。研究了3，1-苯并恶嗪-4-酮在碱性介质中对活性亚甲基化合物即乙酰丙酮的行为，并得到了3-乙酰喹啉。最后的反应被认为是杂环转化反应的说明性模型。

  DOI：

  10.1002/jhet.2389

文献信息

• Quinazolinone Derivatives as Orally Available Ghrelin Receptor Antagonists for the Treatment of Diabetes and Obesity
  作者：Joachim Rudolph、William P. Esler、Stephen O'Connor、Philip D. G. Coish、Philip L. Wickens、Michael Brands、Donald E. Bierer、Brian T. Bloomquist、Georgiy Bondar、Libing Chen、Chih-Yuan Chuang、Thomas H. Claus、Zahra Fathi、Wenlang Fu、Uday R. Khire、James A. Kristie、Xiao-Gao Liu、Derek B. Lowe、Andrea C. McClure、Martin Michels、Astrid A. Ortiz、Philip D. Ramsden、Robert W. Schoenleber、Tatiana E. Shelekhin、Alexandros Vakalopoulos、Weifeng Tang、Lei Wang、Lin Yi、Stephen J. Gardell、James N. Livingston、Laurel J. Sweet、William H. Bullock

  DOI：10.1021/jm070071+

  日期：2007.10.1

  The peptide hormone ghrelin is the endogenous ligand for the type l a growth hormone secretagogue receptor (GHS-R1a) and the only currently known circulating appetite stimulant. GHS-R1a antagonism has therefore been proposed as a potential approach for obesity treatment. More recently, ghrelin has been recognized to also play a role in controlling glucose-induced insulin secretion, which suggests another possible benefit for a GHS-R1a antagonist, namely, the role as an insulin secretagogue with potential value for diabetes treatment. In our laboratories, piperidine- substituted quinazolinone derivatives were identified as a new class of small-molecule GHS-R1a antagonists. Starting from an agonist with poor oral bioavailability, optimization led to potent, selective, and orally bioavailable antagonists. In vivo efficacy evaluation of selected compounds revealed suppression of food intake and body weight reduction as well as glucose-lowering effects mediated by glucose-dependent insulin secretion.
• [EN] QUINAZOLINONE DERIVATIVES USEFUL FOR THE REGULATION OF GLUCOSE HOMEOSTASIS AND FOOD INTAKE<br/>[FR] DERIVES DE LA QUINAZOLINONE UTILES POUR LA REGULATION DE L'HOMEOSTASIE DU GLUCOSE ET DE PRISE D'ALIMENTS
  申请人：BAYER PHARMACEUTICALS CORP

  公开号：WO2006012577A3

  公开（公告）日：2006-09-28
• 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.