7-(4-fluorophenyl)-4-hydroxyquinazoline | 1197199-78-2

• 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: 7-(4-fluorophenyl)-4-hydroxyquinazoline
• 英文别名: 7-(4-fluorophenyl)-3H-quinazolin-4-one
• CAS: 1197199-78-2
• 化学式: C₁₄H₉FN₂O
• 分子量: 240.237
• InChiKey: MUNPCEXJDPYAGO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 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：
  3

反应信息

• 作为反应物：
  描述：

  7-(4-fluorophenyl)-4-hydroxyquinazoline 在 氯化亚砜 、 potassium carbonate 、 N,N-二甲基甲酰胺 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 生成 N-(7-[4-fluorophenyl]quinazolin-4-yl)-4-((1-(phenylthio)ethan-2-yl)amino)-3-nitrobenzenesulfonamide
  参考文献：
  名称：

  Quinazoline Sulfonamides as Dual Binders of the Proteins B-Cell Lymphoma 2 and B-Cell Lymphoma Extra Long with Potent Proapoptotic Cell-Based Activity

  摘要：

  ABT-737 and ABT-263 are potent inhibitors of the BH3 antiapoptotic proteins, Bcl-x(L) and Bcl-2. This class of putative anticancer agents invariantly contains an acylsulfonamide core. We have designed and synthesized a series of novel quinazoline-based inhibitors of Bcl-2 and Bcl-xL that contain a heterocyclic alternative to the acylsulfonamide. These compounds exhibit submicromolar, mechanism-based activity in human small-cell lung carcinoma cell lines in the presence of 10% human serum. This comprises the first successful demonstration of a quinazoline sulfonamide core serving as an effective benzoylsulfonamide bioisostere. Additionally, these novel quinazolines comprise only the second known class of Bcl-2 family protein inhibitors to induce mechanism-based cell death.

  DOI：

  10.1021/jm101596e
• 作为产物：
  描述：

  7-(4-fluorophenyl)-4-aminoquinazoline 在 盐酸 、 水 作用下， 反应 0.5h， 以92%的产率得到7-(4-fluorophenyl)-4-hydroxyquinazoline
  参考文献：
  名称：

  Quinazoline Sulfonamides as Dual Binders of the Proteins B-Cell Lymphoma 2 and B-Cell Lymphoma Extra Long with Potent Proapoptotic Cell-Based Activity

  摘要：

  ABT-737 and ABT-263 are potent inhibitors of the BH3 antiapoptotic proteins, Bcl-x(L) and Bcl-2. This class of putative anticancer agents invariantly contains an acylsulfonamide core. We have designed and synthesized a series of novel quinazoline-based inhibitors of Bcl-2 and Bcl-xL that contain a heterocyclic alternative to the acylsulfonamide. These compounds exhibit submicromolar, mechanism-based activity in human small-cell lung carcinoma cell lines in the presence of 10% human serum. This comprises the first successful demonstration of a quinazoline sulfonamide core serving as an effective benzoylsulfonamide bioisostere. Additionally, these novel quinazolines comprise only the second known class of Bcl-2 family protein inhibitors to induce mechanism-based cell death.

  DOI：

  10.1021/jm101596e

文献信息

• Compounds for Treating Disorders Mediated by Metabotropic Glutamate Receptor 5, and Methods of Use Thereof
  申请人：Hardy Larry Wendell

  公开号：US20110319380A1

  公开（公告）日：2011-12-29

  Provided herein are compounds and methods of synthesis thereof. The compounds set forth herein are useful for the treatment, prevention, and/or management of various disorders, such as neurological disorders, neurodegenerative disorders, neuropsychiatric disorders, disorders of cognition, learning or memory, gastrointestinal disorders, lower urinary tract disorder, and cancer. Compounds set forth herein modulate the activity of metabotropic glutamate receptor 5 (mGluR5) in the central nervous system or the periphery. Pharmaceutical formulations containing the compounds and their methods of use are also provided herein.

  本文提供了化合物及其合成方法。本文中提供的化合物可用于治疗、预防和/或管理各种疾病，如神经系统疾病、神经退行性疾病、神经精神疾病、认知、学习或记忆障碍、胃肠道疾病、下尿路障碍和癌症。本文提供的化合物在中枢神经系统或外周调节代谢性谷氨酸受体5(mGluR5)的活性。本文还提供了含有这些化合物的药物制剂及其使用方法。
• [EN] ARYLSULFONAMIDE COMPOUNDS, COMPOSITIONS AND METHODS OF USE<br/>[FR] COMPOSÉS ARYLSULFONAMIDES, COMPOSITIONS ET PROCÉDÉS D'UTILISATION
  申请人：GENENTECH INC

  公开号：WO2009143246A3

  公开（公告）日：2010-04-29
• ARYLSULFONAMIDE COMPOUNDS, COMPOSITIONS AND METHODS OF USE
  申请人：Baell Jonathan Bayldon

  公开号：US20110098305A1

  公开（公告）日：2011-04-28

  Disclosed are compounds which inhibit the activity of anti-apoptotic protein family members, compositions containing the compounds and uses of the compounds for preparing medicaments for treating diseases during which occurs expression one or more than one of an anti-apoptotic protein family member.
• [EN] COMPOUNDS FOR TREATING DISORDERS MEDIATED BY METABOTROPIC GLUTAMATE RECEPTOR 5, AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS POUR LE TRAITEMENT DES TROUBLES MÉDIÉS PAR LE RÉCEPTEUR MÉTABOTROPIQUE 5 DU GLUTAMATE, ET LEURS MÉTHODES D'UTILISATION
  申请人：SUNOVION PHARMACEUTICALS INC

  公开号：WO2011075699A2

  公开（公告）日：2011-06-23

  Provided herein are compounds and methods of synthesis thereof. The compounds set forth herein are useful for the treatment, prevention, and/or management of various disorders, such as neurological disorders, neurodegenerative disorders, neuropsychiatric disorders, disorders of cognition, learning or memory, gastrointestinal disorders, lower urinary tract disorder, and cancer. Compounds set forth herein modulate the activity of metabotropic glutamate receptor 5 (mGluR5) in the central nervous system or the periphery. Pharmaceutical formulations containing the compounds and their methods of use are also provided herein.
• Quinazoline Sulfonamides as Dual Binders of the Proteins B-Cell Lymphoma 2 and B-Cell Lymphoma Extra Long with Potent Proapoptotic Cell-Based Activity
  作者：Brad E. Sleebs、Peter E. Czabotar、Wayne J. Fairbrother、W. Douglas Fairlie、John A. Flygare、David C. S. Huang、Wilhelmus J. A. Kersten、Michael F. T. Koehler、Guillaume Lessene、Kym Lowes、John P. Parisot、Brian J. Smith、Morey L. Smith、Andrew J. Souers、Ian P. Street、Hong Yang、Jonathan B. Baell

  DOI：10.1021/jm101596e

  日期：2011.3.24

  ABT-737 and ABT-263 are potent inhibitors of the BH3 antiapoptotic proteins, Bcl-x(L) and Bcl-2. This class of putative anticancer agents invariantly contains an acylsulfonamide core. We have designed and synthesized a series of novel quinazoline-based inhibitors of Bcl-2 and Bcl-xL that contain a heterocyclic alternative to the acylsulfonamide. These compounds exhibit submicromolar, mechanism-based activity in human small-cell lung carcinoma cell lines in the presence of 10% human serum. This comprises the first successful demonstration of a quinazoline sulfonamide core serving as an effective benzoylsulfonamide bioisostere. Additionally, these novel quinazolines comprise only the second known class of Bcl-2 family protein inhibitors to induce mechanism-based cell death.