5-溴-4-氯嘧啶-2-胺 | 1044767-99-8

• 物质功能分类: 医药中间体 - 嘧啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 5-溴-4-氯嘧啶-2-胺
• 中文别名: 2-氨基-5-溴-2-氯嘧啶
• 英文名称: 5-bromo-4-chloropyrimidin-2-amine
• CAS: 1044767-99-8
• 化学式: C₄H₃BrClN₃
• 分子量: 208.445
• InChiKey: ZNHIZVRENCRAPA-UHFFFAOYSA-N

物化性质

• 沸点：
  382.3±45.0 °C(Predicted)
• 密度：
  1.960±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  51.8
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933599090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

2-氨基-5-溴-2-氯嘧啶可用作有机合成中间体和医药中间体，主要应用于实验室研发和化工生产过程。

反应信息

• 作为反应物：
  描述：

  5-溴-4-氯嘧啶-2-胺 在 sodium methylate 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 1.5h， 以94%的产率得到2-氨基-5-溴-4-甲氧基嘧啶
  参考文献：
  名称：

  Discovery of a Novel Series of Potent and Orally Bioavailable Phosphoinositide 3-Kinase γ Inhibitors

  摘要：

  The phosphoinositide 3-kinases (PI3Ks) have been linked to an extraordinarily diversified group of cellular functions making these enzymes compelling targets for the treatment of disease. A large body of evidence has linked PI3K gamma to the modulation of autoimmune and inflammatory processes making it an intriguing target for drug discovery. Our high-throughput screening (HTS) campaign revealed two hits that were nominated for further optimization studies. The in vitro activity of the first HTS hit, designated as the sulfonylpiperazine scaffold, was optimized utilizing structure-based design. However, nonoptimal pharmacokinetic properties precluded this series from further studies. An overlay of the X-ray structures of the sulfonylpiperazine scaffold and the second HTS hit within their complexes with PI3K gamma revealed a high degree of overlap. This feature was utilized to design a series of hybrid analogues including advanced leads such as 31 with desirable potency, selectivity, and oral bioavailability.

  DOI：

  10.1021/jm300403a
• 作为产物：
  描述：

  2-氨基-4-氯嘧啶 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 5-溴-4-氯嘧啶-2-胺
  参考文献：
  名称：

  [EN] POTENT AND SELCTIVE COMPOUNDS AS SEROTONIN 1B RECEPTOR MODULATORS
  [FR] COMPOSÉS PUISSANTS ET SÉLECTIFS UTILISÉS EN TANT QUE MODULATEURS DU RÉCEPTEUR DE LA SÉROTONINE 1B

  摘要：

  本发明涉及公式（I）的新化合物作为5-羟色胺受体1B（5-HTR1B）的调节剂。这些化合物在治疗由5-羟色胺受体类型1B（5-HTR1B）介导的疾病和病况方面具有潜在的用途，如癌症，包括血液癌症和实体瘤，呼吸系统疾病和肝脏疾病。

  公开号：

  WO2022074103A1

文献信息

• [EN] OXADIAZOLE INHIBITORS OF LEUKOTRIENE PRODUCTION<br/>[FR] INHIBITEURS À BASE D'OXADIAZOLE DE LA PRODUCTION DES LEUCOTRIÈNES
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2012024150A1

  公开（公告）日：2012-02-23

  The present invention relates to compound of formula (I): or pharmaceutically acceptable salts thereof, wherein R1-R5 are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

  本发明涉及以下化合物的化合物（I）的公式或其药学上可接受的盐，其中R1-R5如本文所定义。该发明还涉及包括这些化合物的药物组合物，使用这些化合物治疗各种疾病和紊乱的方法，制备这些化合物的过程以及在这些过程中有用的中间体。
• OXADIAZOLE INHIBITORS OF LEUKOTRIENE PRODUCTION FOR COMBINATION THERAPY
  申请人：BYLOCK Lars Anders

  公开号：US20130195879A1

  公开（公告）日：2013-08-01

  The present invention relates to combination therapy using compound of formula (I): or pharmaceutically acceptable salts thereof, wherein R 1 -R 5 are as defined herein and an additional pharmaceutically active agent. The invention also relates to pharmaceutical compositions comprising these combinations, and methods of using these combinations in the treatment of various diseases and disorders.

  本发明涉及使用以下化合物的联合疗法（I）的公式： 或其药用可接受盐，其中R1-R5如本文所定义，并且另外包括一种药用活性剂。该发明还涉及包含这些组合物的药物组合物，以及在治疗各种疾病和紊乱中使用这些组合物的方法。
• [EN] ARYL AMINOPYRIMIDINES AS DUAL MERTK AND TYRO3 INHIBITORS AND METHODS THEREOF<br/>[FR] ARYLAMINOPYRIMIDINES UTILISÉES EN TANT QU'INHIBITEURS DOUBLES DE MERTK ET DE TYRO3 ET LEURS PROCÉDÉS
  申请人：UNIV NORTH CAROLINA CHAPEL HILL

  公开号：WO2021097326A1

  公开（公告）日：2021-05-20

  Aminopyrimidine containing compounds that inhibit both Mer tyrosine kinase (MerTK) activity and Tyro3 kinase activity are disclosed herein. Additionally disclosed are methods of synthesis and use of the aminopyrimidine containing compounds as anti-cancer agents, immunostimulatory and immunomodulatory agents, anti-platelet agents, anti-infective agents, and as adjunctive agents.

  本文披露了含有氨基嘧啶的化合物，可以抑制Mer酪氨酸激酶（MerTK）活性和Tyro3激酶活性。此外，还披露了使用含有氨基嘧啶的化合物作为抗癌药物、免疫刺激剂和免疫调节剂、抗血小板药物、抗感染剂以及辅助剂的合成和使用方法。
• 6,5-HETEROCYCLIC PROPARGYLIC ALCOHOL COMPOUNDS AND USES THEREFOR
  申请人：Staben Steven

  公开号：US20120214762A1

  公开（公告）日：2012-08-23

  The invention relates to novel compounds of Formula I: wherein A, Y, R 1 , R 2 and the subscript b each has the meaning as described herein and compounds of Formula I, and stereoisomers, geometric isomers, tautomers, solvates, metabolites, isotopes, pharmaceutically acceptable salts, or prodrugs thereof. Compounds of Formula I and pharmaceutical compositions thereof are useful in the treatment of disease and disorders in which undesired or over-activation of NF-kB signaling is observed.

  这项发明涉及公式I的新化合物： 其中A、Y、R1、R2和下标b各自具有如本文所述的含义，以及公式I的化合物、立体异构体、几何异构体、互变异构体、溶剂合物、代谢物、同位素、药学上可接受的盐或其前药。公式I的化合物及其药物组成物在治疗观察到NF-kB信号通路的不良或过度激活的疾病和紊乱中是有用的。
• Discovery, Optimization, and Evaluation of Potent and Highly Selective PI3Kγ–PI3Kδ Dual Inhibitors
  作者：Hong Jia、Guangxiu Dai、Weiguo Su、Kun Xiao、Jianyang Weng、Zhulin Zhang、Qing Wang、Tianhai Yuan、Fuying Shi、Zheng Zhang、Wei Chen、Yang Sai、Jian Wang、Xiong Li、Yu Cai、Jun Yu、Ping Ren、Jennifer Venable、Tadimeti Rao、James P. Edwards、Scott D. Bembenek

  DOI：10.1021/acs.jmedchem.8b02014

  日期：2019.5.23

  used moiety to impart selectivity in inhibitors for PI3Kγ and PI3Kδ. Guided by molecular docking, this new specificity piece was then linked to the hinge-binding region of the inhibitor using a novel cyclic moiety. Further structure-activity relationship optimization around the hinge region led to the discovery of candidate 26, a highly potent and selective PI3Kγ-PI3Kδ dual inhibitor with favorable drug

  开发了电子密度模型，并用于鉴定喹唑啉酮的新型吡咯烷酮替代物，喹唑啉酮是赋予PI3Kγ和PI3Kδ抑制剂选择性的常用部分。在分子对接的指导下，使用新的环状部分将这一新的特异性片段连接至抑制剂的铰链结合区。围绕铰链区域的进一步的结构-活性关系优化导致了候选化合物26的发现，该候选药物是一种在临床前物种中具有良好药物代谢和药代动力学特性的高效PI3Kγ-PI3Kδ双重抑制剂。