4-甲氧基嘧啶-5-基硼酸 | 909187-37-7

• 物质功能分类: 化学试剂 - 有机试剂 - 硼酸
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 4-甲氧基嘧啶-5-基硼酸
• 中文别名: （4-甲氧基嘧啶-5-基）硼酸
• 英文名称: (4-methoxypyrimidin-5-yl)boronic acid
• CAS: 909187-37-7
• 化学式: C₅H₇BN₂O₃
• 分子量: 153.933
• InChiKey: SIHFIKAJVVQLMX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.83
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  75.5
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P330,P363,P501
• 危险性描述：
  H302,H312,H332

反应信息

• 作为反应物：
  描述：

  4-甲氧基嘧啶-5-基硼酸 、 2-bromo-5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-2-methyl-phenyl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazole-4-one 在 potassium phosphate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-2-methyl-phenyl)-1-isopropyl-2-(4-methoxy-pyrimidin-5-yl)-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one
  参考文献：
  名称：

  In vitro and in vivo characterization of a novel, highly potent p53-MDM2 inhibitor

  摘要：

  Small molecule inhibitors of the p53-MDM2 protein complex are under intense investigation in clinical trials as anti-cancer agents, including our first generation inhibitor NVP-CGM097. We recently described the rational design of a novel pyrazolopyrrolidinone core as a new lead structure and now we report on the synthesis and optimization of this to provide a highly potent lead compound. This new compound displayed excellent oral efficacy in our preclinical mechanistic in vivo model and marked a significant milestone towards the identification of our second generation clinical candidate NVP-HDM201.

  DOI：

  10.1016/j.bmcl.2018.08.027
• 作为产物：
  描述：

  5-溴-4-甲氧基-嘧啶 在 正丁基锂 、 硼酸三异丙酯 作用下， 以 四氢呋喃 为溶剂， 反应 1.17h， 生成 4-甲氧基嘧啶-5-基硼酸
  参考文献：
  名称：

  [EN] CHEMICAL COMPOUNDS
  [FR] COMPOSÉS CHIMIQUES

  摘要：

  本发明涉及取代喹啉衍生物。具体而言，本发明涉及根据公式I的化合物：其中R，R1，R2，R3和R4按如下定义。本发明的化合物是乳酸脱氢酶A的抑制剂，可用于治疗癌症和与肿瘤细胞代谢有关的疾病，例如癌症，更具体地说是乳腺癌、结肠癌、前列腺癌和肺癌。因此，本发明进一步涉及包含本发明化合物的药物组合物。本发明还进一步涉及使用本发明的化合物或包含本发明化合物的药物组合物来抑制乳酸脱氢酶A活性和治疗与之相关的疾病的方法。

  公开号：

  WO2013096153A1

文献信息

• Phthalazine, aza- and diaza-phthalazine compounds and methods of use
  申请人：Tasker Andrew

  公开号：US20060199817A1

  公开（公告）日：2006-09-07

  The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation and related conditions. The compounds have a general Formula I wherein A 1 , A 2 , B, R 1 , R 2 , R 3 and R 4 are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, uses of such compounds and compositions for treatment of kinase mediated diseases including rheumatoid arthritis, psoriasis and other inflammation disorders, as well as intermediates and processes useful for the preparation of compounds of Formula I.

  本发明包括一类新的化合物，用于预防和治疗蛋白激酶介导的疾病，包括炎症及相关状况。这些化合物的通用公式为I 其中A 1 ，A 2 ，B，R 1 ，R 2 ，R 3 和R 4 在此定义。该发明还包括包括一个或多个I公式化合物的药物组合物，以及使用这些化合物和组合物治疗激酶介导的疾病，包括类风湿性关节炎，银屑病和其他炎症性疾病，以及用于制备I公式化合物的中间体和工艺。
• PYRROLOPYRIMIDINES AS CFTR POTENTIATORS
  申请人：CYSTIC FIBROSIS FOUNDATION THERAPEUTICS, INC.

  公开号：US20180141954A1

  公开（公告）日：2018-05-24

  The present invention relates to compounds of Formula I, wherein R 1a , R 1b , R 2 , R 3 , R 4 , W, Y, and Z are as described herein, and pharmaceutically acceptable salts thereof. The compounds are potentiators of Cystic Fibrosis Transmembrane conductance Regulator (CFTR). The invention also discloses pharmaceutical compositions comprising the compound, optionally in combination with additional therapeutic agents, and methods of potentiating, in mammals, including humans, CFTR by administration of the compounds. These compounds are useful for the treatment of cystic fibrosis (CF), asthma, bronchiectasis, chronic obstructive pulmonary disease (COPD), constipation, Diabetes mellitus, dry eye disease, pancreatitis, rhinosinusitis, Sjögren's Syndrome, and other CFTR associated disorders.

  本发明涉及式I的化合物，其中R1a、R1b、R2、R3、R4、W、Y和Z如本文所述，并且其药学上可接受的盐。这些化合物是囊性纤维化跨膜传导调节器（CFTR）的增效剂。本发明还揭示了包括该化合物的药物组合物，可选地与额外治疗剂结合，并通过给予这些化合物来增强哺乳动物（包括人类）CFTR的方法。这些化合物可用于治疗囊性纤维化（CF）、哮喘、支气管扩张、慢性阻塞性肺病（COPD）、便秘、糖尿病、干眼症、胰腺炎、鼻窦炎、Sjögren综合征和其他与CFTR相关的疾病。
• Design of Potent and Selective Inhibitors to Overcome Clinical Anaplastic Lymphoma Kinase Mutations Resistant to Crizotinib
  作者：Qinhua Huang、Ted W. Johnson、Simon Bailey、Alexei Brooun、Kevin D. Bunker、Benjamin J. Burke、Michael R. Collins、Andrew S. Cook、J. Jean Cui、Kevin N. Dack、Judith G. Deal、Ya-Li Deng、Dac Dinh、Lars D. Engstrom、Mingying He、Jacqui Hoffman、Robert L. Hoffman、Patrick S. Johnson、Robert S. Kania、Hieu Lam、Justine L. Lam、Phuong T. Le、Qiuhua Li、Laura Lingardo、Wei Liu、Melissa West Lu、Michele McTigue、Cynthia L. Palmer、Paul F. Richardson、Neal W. Sach、Hong Shen、Tod Smeal、Graham L. Smith、Albert E. Stewart、Sergei Timofeevski、Konstantinos Tsaparikos、Hui Wang、Huichun Zhu、Jinjiang Zhu、Helen Y. Zou、Martin P. Edwards

  DOI：10.1021/jm401805h

  日期：2014.2.27

  Crizotinib (1), an anaplastic lymphoma kinase (ALK) receptor tyrosine kinase inhibitor approved by the U.S. Food and Drug Administration in 2011, is efficacious in ALK and ROS positive patients. Under pressure of crizotinib treatment, point mutations arise in the kinase domain of ALK, resulting in resistance and progressive disease. The successful application of both structure-based and lipophilic-efficiency-focused

  Crizotinib（1）是间变性淋巴瘤激酶（ALK）受体酪氨酸激酶抑制剂，于2011年获得美国食品和药物管理局（FDA）批准，对ALK和ROS阳性患者有效。在克唑替尼治疗的压力下，ALK激酶结构域中出现点突变，导致耐药性和进行性疾病。以结构为基础和以亲脂性效率为中心的药物设计的成功应用产生了氨基吡啶8e，该氨基吡啶在多种工程化的ALK突变细胞系中均有效，并且在耐克唑替尼的细胞中显示出合适的临床前药代动力学和强大的肿瘤生长抑制作用线（H3122-L1196M）。
• Phthalazine compounds and methods of use
  申请人：Amgen Inc.

  公开号：US07759337B2

  公开（公告）日：2010-07-20

  The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation and related conditions. The compounds have a general Formula I wherein B, R1, R2, R3, R4 and R5 are d.efined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, uses of such compounds and compositions for treatment of kinase mediated diseases including rheumatoid arthritis, psoriasis and other inflammation disorders, as well as intermediates and processes useful for the preparation of compounds of Formula I.

  本发明涉及一种新类化合物，用于预防和治疗蛋白激酶介导的疾病，包括炎症和相关疾病。该化合物具有通式I，其中B，R1，R2，R3，R4和R5在此被定义。本发明还包括药物组合物，包括一个或多个通式I的化合物，使用这些化合物和组合物治疗激酶介导的疾病，包括类风湿性关节炎、牛皮癣和其他炎症性疾病，以及有用于制备通式I化合物的中间体和过程。