6-bromo-2-(o-tolyl)-4H-benzo[d][1,3]oxazin-4-one | 404835-95-6

• 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-(o-tolyl)-4H-benzo[d][1,3]oxazin-4-one
• 英文别名: 6-Bromo-2-(2-methylphenyl)-4H-3,1-benzoxazin-4-one；6-bromo-2-(2-methylphenyl)-3,1-benzoxazin-4-one
• CAS: 404835-95-6
• 化学式: C₁₅H₁₀BrNO₂
• 分子量: 316.154
• InChiKey: HXUXCQIHLHRMSX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 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-(o-tolyl)-4H-benzo[d][1,3]oxazin-4-one 在 bis-triphenylphosphine-palladium(II) chloride 、 四(三苯基膦)钯 、 potassium carbonate 、 三氟乙酸 、 lithium hydroxide 作用下， 以 二氯甲烷 、 甲苯 、 乙腈 为溶剂， 反应 35.0h， 生成 (S)-6-(4-fluorobenzoyl)-3-((1-isopropylpiperidin-3-yl)-methyl)-2-(o-tolyl)quinazolin-4(3H)-one
  参考文献：
  名称：

  QUINAZOLINONE DERIVATIVES USEFUL FOR IMAGING

  摘要：

  该化合物包括喹唑啉酮衍生物，以及识别和使用成像试剂的方法。该化合物具有一般式I：其中R2从卤素、卤代烷基、烷基、羟基烷基和氨基烷基中选择；X从酯、羰基或-CH2-中选择；R1从单环或双环芳香或杂芳香环系统中选择，其中单环或双环芳香或杂芳香环系统可以选择性地被卤素、烷基、硝基、烷氧基、氨基取代；R3从一个或两个卤素、卤代烷基、烷基、硝基、羟基烷基和烷基对磺酸酯中选择；或其药学上可接受的盐。本发明的化合物可用于前列腺癌或其他形式癌症的检测、诊断和/或分期，并且还可用于心脏疾病。

  公开号：

  US20200031821A1
• 作为产物：
  描述：

  邻甲基苯甲酰氯 、 2-氨基-5-溴苯甲酸 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以70%的产率得到6-bromo-2-(o-tolyl)-4H-benzo[d][1,3]oxazin-4-one
  参考文献：
  名称：

  QUINAZOLINONE DERIVATIVES USEFUL FOR IMAGING

  摘要：

  该化合物包括喹唑啉酮衍生物，以及识别和使用成像试剂的方法。该化合物具有一般式I：其中R2从卤素、卤代烷基、烷基、羟基烷基和氨基烷基中选择；X从酯、羰基或-CH2-中选择；R1从单环或双环芳香或杂芳香环系统中选择，其中单环或双环芳香或杂芳香环系统可以选择性地被卤素、烷基、硝基、烷氧基、氨基取代；R3从一个或两个卤素、卤代烷基、烷基、硝基、羟基烷基和烷基对磺酸酯中选择；或其药学上可接受的盐。本发明的化合物可用于前列腺癌或其他形式癌症的检测、诊断和/或分期，并且还可用于心脏疾病。

  公开号：

  US20200031821A1

文献信息

• Quinazolinone derivatives useful for imaging
  申请人：LONDON HEALTH SCIENCES CENTRE RESEARCH INC.

  公开号：US11186571B2

  公开（公告）日：2021-11-30

  Compounds comprising quinazolinone derivatives and methods of identification and use of imaging agents. The compounds have the general formula I: wherein R2 is selected from halogen, halosubstituted alkyl, alkyl, hydroxyl-alkyl, and amino-alkyl; X is selected from ester, carbonyl or —CH2—; R1 is selected from mono-, or bicyclic aromatic or heteroaromatic ring systems, wherein the mono-, or bicyclic aromatic or heteroaromatic ring systems are optionally substituted by halo, alkyl, nitro, alkoxy, amino; R3 is selected from one or two halo, halosubstituted alkyl, alkyl, nitro, hydroxyl-alkyl, and alkyl tosylate; or a pharmaceutically acceptable salt thereof. The compounds of the present invention may be used for detection, diagnosis and/or staging of prostate or other forms of cancer, and may also be used for cardiac disease.

  包含喹唑啉酮衍生物的化合物以及成像剂的鉴定和使用方法。这些化合物具有通式 I：其中 R2 选自卤素、卤代烷基、烷基、羟基-烷基和氨基-烷基；X 选自酯、羰基或-CH2-；R1 选自单环或双环芳香族或杂芳环系，其中单环或双环芳香族或杂芳环系任选被卤素、烷基、硝基、烷氧基、氨基取代；R3 选自一个或两个卤代、卤代烷基、烷基、硝基、羟基-烷基和烷基甲苯磺酸盐；或其药学上可接受的盐。本发明的化合物可用于前列腺癌或其他形式癌症的检测、诊断和/或分期，也可用于心脏疾病。
• 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
• Development of Candidates for Positron Emission Tomography (PET) Imaging of Ghrelin Receptor in Disease: Design, Synthesis, and Evaluation of Fluorine-Bearing Quinazolinone Derivatives
  作者：Jinqiang Hou、Michael S. Kovacs、Savita Dhanvantari、Leonard G. Luyt

  DOI：10.1021/acs.jmedchem.7b01754

  日期：2018.2.8

  Molecular imaging with positron emission tomography (PET) is an attractive platform for noninvasive detection and assessment of disease. The development of a PET imaging agent targeting the ghrelin receptor (growth hormone secretagogue receptor type 1a or GHS-R1a) has the potential to lead to the detection and assessment of the higher than normal expression of GHS-R1a in diseases such as prostate, breast, and ovarian cancer. To enable the development of F-18 radiopharmaceuticals, we have designed and synthesized three series of quinazolinone derivatives, resulting in the identification of two compound (5i, 17) with subnanomolar binding affinity and one fluorine-bearing compound (10b) with picomolar binding affinity (20 pM), representing the highest binding affinity for GHS-R1a reported to date. Two lead compounds (5b, IC50 = 20.6 nM; 5e, IC50 = 9.3 nM) were successfully F-18-radiolabeled with radiochemical purity of greater than 99%. Molecular modeling studies were performed to shed light on ligand-receptor interactions.
• [EN] QUINAZOLINONE DERIVATIVES USEFUL FOR IMAGING<br/>[FR] DÉRIVÉS DE QUINAZOLINONE UTILES POUR L'IMAGERIE
  申请人：LONDON HEALTH SCI CT RES INC

  公开号：WO2018184115A1

  公开（公告）日：2018-10-11

  Compounds comprising quinazolinone derivatives and methods of identification and use of imaging agents. The compounds have the general formula I: wherein R2 is selected from halogen, halosubstituted alkyl, alkyl, hydroxyl-alkyl, and amino-alkyl; X is selected from ester, carbonyl or -CH2-; R1 is selected from mono-, or bicyclic aromatic or heteroaromatic ring systems, wherein the mono-, or bicyclic aromatic or heteroaromatic ring systems are optionally substituted by halo, alkyl, nitro, alkoxy, amino; R3 is selected from one or two halo, halosubstituted alkyl, alkyl, nitro, hydroxyl- alkyl, and alkyl tosylate; or a pharmaceutically acceptable salt thereof. The compounds of the present invention may be used for detection, diagnosis and/or staging of prostate or other forms of cancer, and may also be used for cardiac disease.