5-溴-2-氯-4-乙氧基嘧啶

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 5-溴-2-氯-4-乙氧基嘧啶
• 英文名称: 5-bromo-2-chloro-4-ethoxypyrimidine
• 英文别名: 5-Bromo-2-chloro-4-ethoxypyrimidine
• 化学式: C₆H₆BrClN₂O
• mdl: MFCD21789322
• 分子量: 237.483
• InChiKey: JLHYOQWWHLEBDO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  35
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-溴-2-氯-4-乙氧基嘧啶 在 四氧化锇 、 四(三苯基膦)钯 、 sodium hydride 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 53.75h， 生成 N-((4-ethoxy-2-((2-methyl-[1,1'-biphenyl]-3-yl)methoxy)pyrimidin-5-yl)methyl)-N-methylglycine
  参考文献：
  名称：

  [EN] PYRIMIDINE DERIVATIVES AS INHIBITORS OF PD1/PD-L1 ACTIVATION
  [FR] DÉRIVÉS DE PYRIMIDINE UTILISÉS EN TANT QU'INHIBITEURS DE L'ACTIVATION DE PD1/PD-L1

  摘要：

  公式Ib、公式Ia和公式I的化合物及其多型体、立体异构体、互变异构体、前药、溶剂合物和其药用可接受盐在本文中进行描述。还描述了制备公式Ib、公式Ia和公式I化合物的过程。本文描述的化合物、其多型体、立体异构体、互变异构体、前药、溶剂合物和其药用可接受盐是PD-1/PD-L1激活的抑制剂，为2-(苄氧基)嘧啶衍生物。

  公开号：

  WO2019087214A1
• 作为产物：
  描述：

  5-溴-2,4-二氯嘧啶 、 sodium ethanolate 以 乙醇 为溶剂， 反应 6.0h， 以80%的产率得到5-溴-2-氯-4-乙氧基嘧啶
  参考文献：
  名称：

  [EN] PYRIMIDINE DERIVATIVES AS INHIBITORS OF PD1/PD-L1 ACTIVATION
  [FR] DÉRIVÉS DE PYRIMIDINE UTILISÉS EN TANT QU'INHIBITEURS DE L'ACTIVATION DE PD1/PD-L1

  摘要：

  公式Ib、公式Ia和公式I的化合物及其多型体、立体异构体、互变异构体、前药、溶剂合物和其药用可接受盐在本文中进行描述。还描述了制备公式Ib、公式Ia和公式I化合物的过程。本文描述的化合物、其多型体、立体异构体、互变异构体、前药、溶剂合物和其药用可接受盐是PD-1/PD-L1激活的抑制剂，为2-(苄氧基)嘧啶衍生物。

  公开号：

  WO2019087214A1

文献信息

• [EN] NOVEL COMPOUNDS AS REARRANGED DURING TRANSFECTION (RET) INHIBITORS<br/>[FR] NOUVEAUX COMPOSÉS UTILISÉS COMME INHIBITEURS DE LA KINASE RÉARRANGÉE AU COURS DE LA TRANSFECTION (RET)
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2016037578A1

  公开（公告）日：2016-03-17

  This invention relates to novel compounds which are inhibitors of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and/or secretion and/or abdominal disorders or diseases and/or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, medullary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, papillary thyroid cancer, brain tumors, peritoneal cavity cancer, solid tumors, other lung cancer, head and neck cancer, gliomas, neuroblastomas, Von Hippel-Lindau Syndrome and kidney tumors, breast cancer, fallopian tube cancer, ovarian cancer, transitional cell cancer, prostate cancer, cancer of the esophagus and gastroesophageal junction, biliary cancer, adenocarcinoma, and any malignancy with increased RET kinase activity.

  这项发明涉及一种新型化合物，这些化合物是重排转位过程中的抑制剂（RET）激酶，包含它们的药物组合物，它们的制备方法，以及它们在治疗中的使用，单独或结合使用，用于规范胃肠敏感性、蠕动和/或分泌以及/或腹部紊乱或疾病和/或与RET功能障碍相关的疾病或调节RET活性可能具有治疗益处的治疗，包括但不限于所有分类的肠易激综合征（IBS），包括以腹泻为主、以便秘为主或交替排便模式、功能性腹胀、功能性便秘、功能性腹泻、未特指的功能性肠道障碍、功能性腹痛综合征、慢性特发性便秘、功能性食管障碍、功能性胃十二指肠障碍、功能性肛门疼痛、炎症性肠病、非小细胞肺癌、肝细胞癌、结肠癌、髓样甲状腺癌、滤泡性甲状腺癌、间变性甲状腺癌、乳头状甲状腺癌、脑肿瘤、腹腔癌、实体肿瘤、其他肺癌、头颈癌、神经胶质瘤、神经母细胞瘤、冯·希普-林道氏综合征和肾肿瘤、乳腺癌、输卵管癌、卵巢癌、移行细胞癌、前列腺癌、食管和食管胃交界处癌症、胆道癌、腺癌，以及任何具有增加RET激酶活性的恶性肿瘤。
• Heteroaryl-substituted alkyne compounds and method of use
  申请人：Chaffee C. Stuart

  公开号：US20060217380A1

  公开（公告）日：2006-09-28

  The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation, cancer and related conditions. The compounds have a general Formula I wherein A 1 , A 2 , A 3 , A 4 , R 1 and R 2 are defined herein. Accordingly, the invention also comprises pharmaceutical compositions comprising the compounds of the invention, methods for the prophylaxis and treatment of kinase mediated diseases using the compounds and compositions of the invention, and intermediates and processes useful for the preparation of compounds of the invention.

  本发明涉及一种新型化合物类别，可用于预防和治疗蛋白激酶介导的疾病，包括炎症、癌症和相关病症。该化合物具有一般式I，其中A1、A2、A3、A4、R1和R2如本文所定义。因此，本发明还涉及包含本发明化合物的制药组合物，使用本发明化合物和组合物预防和治疗激酶介导的疾病的方法，以及用于制备本发明化合物的中间体和过程。
• Compounds as rearranged during transfection (RET) inhibitors
  申请人：GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED

  公开号：US10294236B2

  公开（公告）日：2019-05-21

  This invention relates to novel compounds which are inhibitors of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and/or secretion and/or abdominal disorders or diseases and/or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, medullary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, papillary thyroid cancer, brain tumors, peritoneal cavity cancer, solid tumors, other lung cancer, head and neck cancer, gliomas, neuroblastomas, Von Hippel-Lindau Syndrome and kidney tumors, breast cancer, fallopian tube cancer, ovarian cancer, transitional cell cancer, prostate cancer, cancer of the esophagus and gastroesophageal junction, biliary cancer, adenocarcinoma, and any malignancy with increased RET kinase activity.

  本发明涉及作为转染过程中重排（RET）激酶抑制剂的新型化合物、含有这些化合物的药物组合物、制备这些化合物的工艺，以及这些化合物在治疗中的用途（单独使用或联合使用），用于使胃肠道敏感性正常化、肠易激综合征（IBS）的所有分类，包括腹泻为主、便秘为主或交替大便模式、功能性腹胀、功能性便秘、功能性腹泻、不明功能性肠紊乱、功能性腹痛综合征、慢性特发性便秘、功能性食道疾病、功能性胃十二指肠疾病、功能性肛门直肠痛、炎症性肠病、增殖性疾病，如非小细胞肺癌、肝细胞癌、结肠直肠癌、甲状腺髓样细胞癌、滤泡性甲状腺癌、无细胞甲状腺癌、甲状腺乳头状癌、脑肿瘤、腹腔癌、实体瘤、其他肺癌、头颈部肿瘤、胶质瘤、神经母细胞瘤、冯-希佩尔-林道综合征和肾肿瘤、乳腺癌、输卵管癌、卵巢癌、过渡性细胞癌、前列腺癌、食道癌和胃食道交界处癌、胆道癌、腺癌以及任何 RET 激酶活性增高的恶性肿瘤。
• NOVEL COMPOUNDS AS REARRANGED DURING TRANSFECTION (RET) INHIBITORS
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：EP3191449A1

  公开（公告）日：2017-07-19
• COMPOUNDS AS REARRANGED DURING TRANSFECTION (RET) INHIBITORS
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：EP3191449B1

  公开（公告）日：2020-07-01