3-(3-bromophenyl)-1H-quinoxalin-2-one | 245554-82-9

• 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: 3-(3-bromophenyl)-1H-quinoxalin-2-one
• 英文别名: 3-(3-vromophenyl)quinoxalin-2(1H)-one；3-(3-bromophenyl)-1,2-dihydro-2-quinoxalinone；3-(3-Bromophenyl)quinoxalin-2-one
• CAS: 245554-82-9
• 化学式: C₁₄H₉BrN₂O
• 分子量: 301.142
• InChiKey: LJMBUIKFRPYIPE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  41.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(3-bromophenyl)-1H-quinoxalin-2-one 在 palladium diacetate racemic-2-(di-tert-butylphosphino)-1,1′-binaphthyl 、 吡啶 、 盐酸 、 偶氮二甲酸二异丙酯 、 水 、 caesium carbonate 、 三苯基膦 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 65.92h， 生成
  参考文献：
  名称：

  [EN] BISMACROKYCLIC COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS
  [FR] COMPOSÉS BISMACROCYCLIQUES À TITRE D'INHIBITEURS DU VIRUS DE L'HÉPATITE C

  摘要：

  公开号：

  WO2011049908A3
• 作为产物：
  描述：

  3-(3-bromophenyl)-3,4-dihydro-1H-quinoxalin-2-one 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 甲苯 为溶剂， 反应 3.0h， 生成 3-(3-bromophenyl)-1H-quinoxalin-2-one
  参考文献：
  名称：

  Design, Synthesis, and Biological Activity of Potent and Selective Inhibitors of Blood Coagulation Factor Xa

  摘要：

  Factor Xa (FXa) has materialized as a key enzyme for the intervention of the blood coagulation cascade and for the development of new antithrombotic agents. FXa is the lone enzyme responsible for the production of thrombin and therefore is an attractive target for the control of thrombus formation. We have designed and synthesized a unique series of quinoxalinone FXa inhibitors. This series resulted in 3-{4-[5-((2S,6R)-2,6-dimethylpiperidin-1-yl)pentyl]-3oxo-3,4-dihydroquinoxolin-2-yl}benzamidine (35) with 0.83 nM activity against FXa and excellent selectivity over similar serine proteases. An X-ray crystal structure of compound 35 bound to trypsin along with molecular modeling has led to a predicted binding conformation of compound 35 in FXa. Compound 35 has also been proven to be efficacious in vivo in both the rabbit veno-venous shunt and dog electrolytic injury models. In addition, it was shown that compound 35 did not significantly increase bleeding times in a rabbit model except at the highest doses and plasma concentrations were elevated in a dose dependent manner following a bolus dose and continuous intravenous infusion.

  DOI：

  10.1021/jm0497491

文献信息

• [EN] QUINOXALINE-CONTAINING COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS<br/>[FR] COMPOSÉS CONTENANT DE LA QUINOXALINE EN TANT QU'INHIBITEURS DU VIRUS DE L'HÉPATITE C
  申请人：ENANTA PHARM INC

  公开号：WO2009064975A1

  公开（公告）日：2009-05-22

  The present invention discloses compounds of formula I and II or pharmaceutically acceptable salts, esters, or prodrugs thereof which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

  本发明公开了抑制丝氨酸蛋白酶活性的I和II公式化合物，或其药物可接受的盐、酯或前药，尤其是抑制丙型肝炎病毒（HCV）NS3-NS4A蛋白酶的活性。因此，本发明的化合物干扰丙型肝炎病毒的生命周期，并且也用作抗病毒剂。本发明进一步涉及包含前述化合物的药物组合物，用于给患有HCV感染的主体进行管理。本发明还涉及通过管理包含本发明化合物的药物组合物来治疗主体中的HCV感染的方法。
• α-Keto Acids as Triggers and Partners for the Synthesis of Quinazolinones, Quinoxalinones, Benzooxazinones, and Benzothiazoles in Water
  作者：Jian Huang、Wei Chen、Jiazhi Liang、Qin Yang、Yan Fan、Mu-Wang Chen、Yiyuan Peng

  DOI：10.1021/acs.joc.1c01497

  日期：2021.11.5

  the synthesis of quinazolinones, quinoxalinones, benzooxazinones, and benzothiazoles from the reactions of α-keto acids with 2-aminobenzamides, benzene-1,2-diamines, 2-aminophenols, and 2-aminobenzenethiols, respectively, is described. The reactions were conducted under catalyst-free conditions, using water as the sole solvent with no additive required, and successfully applied to the synthesis of sildenafil

  由 α-酮酸分别与 2-氨基苯甲酰胺、苯-1,2-二胺、2-氨基苯酚和 2-氨基苯硫醇反应合成喹唑啉酮、喹喔啉酮、苯并恶嗪酮和苯并噻唑的通用有效方法是描述。该反应在无催化剂条件下进行，以水为唯一溶剂，无需任何添加剂，成功应用于西地那非的合成。更重要的是，这些反应可以大规模进行，产物可以很容易地通过过滤和乙醇洗涤（或结晶）进行纯化。
• High-Potency Phenylquinoxalinone Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Activators
  作者：Jung-Ho Son、Jie S. Zhu、Puay-Wah Phuan、Onur Cil、Andrew P. Teuthorn、Colton K. Ku、Sujin Lee、Alan S. Verkman、Mark J. Kurth

  DOI：10.1021/acs.jmedchem.6b01759

  日期：2017.3.23

  We previously identified phenylquinoxalinone CFTRact-J027 (4) as a cystic fibrosis transmembrane conductance regulator (CFTR) activator with an EC50 of ∼200 nM and demonstrated its therapeutic efficacy in mouse models of constipation. Here, structure–activity studies were done on 36 synthesized phenylquinoxalinone analogs to identify compounds with improved potency and altered metabolic stability.

  我们之前鉴定出苯基喹喔啉酮CFTR act -J027（4）为EC 50为〜200 nM的囊性纤维化跨膜电导调节剂（CFTR）激活剂，并证明了其在便秘小鼠模型中的治疗效果。在这里，对36种合成的苯基喹喔啉酮类似物进行了结构活性研究，以鉴定具有增强的效力和改变的代谢稳定性的化合物。苯基喹喔啉酮核的合成通常通过1,2-苯二胺与取代的苯基氧乙酸酯的缩合来完成。结构活性研究除其他功能外，还确定了在3-芳基上适当定位的硝基部分的优先性质。与之相比，合成的类似物显示出更高的CFTR激活能力4的EC 50降至21 nM，具有更高的代谢稳定性。CFTR激活剂在便秘，干眼症，胆汁淤积性肝病和炎症性肺疾病中具有潜在的治疗适应症。
• [EN] DIFLUOROMETHYL-CONTAINING MACROCYCLIC COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS<br/>[FR] COMPOSÉS MACROCYCLIQUES CONTENANT DU DIFLUOROMÉTHYLE COMME INHIBITEURS DU VIRUS DE L'HÉPATITE C
  申请人：ENANTA PHARM INC

  公开号：WO2009134987A1

  公开（公告）日：2009-11-05

  The present invention discloses compounds of formula I or pharmaceutically acceptable salts, esters, or prodrugs thereof: (formula I), which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

  本发明揭示了化合物I或其药学上可接受的盐、酯或前药：（化合物I）的结构，其抑制丝氨酸蛋白酶活性，特别是丝氨酸蛋白酶NS3-NS4A的活性。因此，本发明的化合物干扰了丙型肝炎病毒的生命周期，并且还可用作抗病毒剂。本发明还涉及包含上述化合物的制药组合物，用于治疗患有丙型肝炎病毒感染的受试者。本发明还涉及通过给予包含本发明化合物的制药组合物来治疗受试者的丙型肝炎感染的方法。
• Quinoxalinones as serine protease inhibitors
  申请人：——

  公开号：US20020086866A1

  公开（公告）日：2002-07-04

  This invention discloses quinoxalinones which display inhibitory effects on serine proteases such as factor Xa, thrombin, and/or factor VIIa. The invention also discloses pharmaceutically acceptable salts and prodrugs of the compounds, pharmaceutically acceptable compositions comprising the compounds, their salts or prodrugs, and methods of using them as therapeutic agents for treating or preventing disease states in mammals characterized by abnormal thrombosis.

  这项发明公开了对丝氨酸蛋白酶（如Xa因子、凝血酶和/或VIIa因子）具有抑制作用的喹诺酮。该发明还公开了该化合物的药物可接受的盐和前药、包含该化合物、其盐或前药的药物可接受的组合物，以及将其作为治疗剂用于治疗或预防哺乳动物的疾病状态，这些状态以异常血栓形成为特征的方法。