(5-bromo-2-chloro-pyrimidin-4-yl)-(pyridin-2-ylmethyl)-amine | 719312-04-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (5-bromo-2-chloro-pyrimidin-4-yl)-(pyridin-2-ylmethyl)-amine
• 英文别名: 5-bromo-2-chloro-N-(pyridin-2-ylmethyl)pyrimidin-4-amine
• CAS: 719312-04-6
• 化学式: C₁₀H₈BrClN₄
• 分子量: 299.557
• InChiKey: NEOIWCWGNIIKBX-UHFFFAOYSA-N

物化性质

• 沸点：
  463.8±40.0 °C(Predicted)
• 密度：
  1.688±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  50.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-氨基-1,3-二氢吲哚-2-酮 、 (5-bromo-2-chloro-pyrimidin-4-yl)-(pyridin-2-ylmethyl)-amine 在 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 为溶剂， 生成 5-(5-Bromo-4-(pyridin-2-ylmethylamino)pyrimidin-2-ylamino)indolin-2-one
  参考文献：
  名称：

  Trifluoromethylpyrimidine-based inhibitors of proline-rich tyrosine kinase 2 (PYK2): Structure–activity relationships and strategies for the elimination of reactive metabolite formation

  摘要：

  The synthesis and SAR for a series of diaminopyrimidines as PYK2 inhibitors are described. Using a combination of library and traditional medicinal chemistry techniques, a FAK-selective chemical series was transformed into compounds possessing good PYK2 potency and 10- to 20-fold selectivity against FAK. Subsequent studies found that the majority of the compounds were positive in a reactive metabolite assay, an indicator for potential toxicological liabilities. Based on the proposed mechanism for bioactivation, as well as a combination of structure-based drug design and traditional medicinal chemistry techniques, a follow-up series of PYK2 inhibitors was identified that maintained PYK2 potency, FAK selectivity and HLM stability, yet were negative in the RM assay.

  DOI：

  10.1016/j.bmcl.2008.10.030
• 作为产物：
  描述：

  2-氨甲基吡啶 、 5-溴-2,4-二氯嘧啶 在 N,N-二异丙基乙胺 作用下， 以 异丙醇 为溶剂， 以82 %的产率得到(5-bromo-2-chloro-pyrimidin-4-yl)-(pyridin-2-ylmethyl)-amine
  参考文献：
  名称：

  作为 EGFRC797S 酪氨酸激酶抑制剂的新型嘧啶衍生物的设计、合成和评价

  摘要：

  表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）在非小细胞肺癌治疗中的临床应用因EGFR C797S突变引起的耐药性而受到限制。因此，为了克服耐药性，我们设计并合成了一系列2-氨基嘧啶衍生物作为EGFR C797S -TKI。在这些化合物中，化合物A5和A13对KC-0116(EGFR del19/T790M/C797S )细胞系表现出显着的高选择性抗增殖活性。A5抑制EGFR磷酸化并诱导KC-0116细胞凋亡，使KC-0116细胞阻滞于G2/M期。分子对接结果显示A5布加替尼以类似的模式与 EGFR 结合。除了与 Met793 残基形成两个重要的氢键外，A5还与 Lys745 残基形成氢键，这可能对 EGFR del19/T790M/C797S 的有效抑制活性发挥重要作用。基于这些结果，A5被证明是有效的可逆EGFR C797S -TKI，可以进一步开发。

  DOI：

  10.1016/j.bmcl.2023.129381

文献信息

• Compound for the treatment of abnormal cell growth
  申请人：Pfizer Inc

  公开号：US20040220177A1

  公开（公告）日：2004-11-04

  The invention relates to compounds of the formula 1 1 and to pharmaceutically acceptable salts, prodrugs and solvates thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , n, A and B are as defined herein. The invention also relates to methods of treating abnormal cell growth in mammals by administering the compounds of formula 1 and to pharmaceutical compositions for treating such disorders, which contain the compounds of formula 1. The invention also relates to methods of preparing the compounds of formula 1.

  本发明涉及公式11的化合物，以及其药物可接受的盐、前药和溶剂化物，其中R1、R2、R3、R4、R5、n、A和B的定义如本文所述。本发明还涉及通过给予公式1的化合物治疗哺乳动物异常细胞生长的方法，并涉及用于治疗此类疾病的制药组合物，其中包含公式1的化合物。本发明还涉及制备公式1的化合物的方法。
• HETEROCYCLIC DERIVATIVES AND METHODS OF USE THEREOF
  申请人：Boriack-Sjodin Ann

  公开号：US20100137313A1

  公开（公告）日：2010-06-03

  Compounds of formula (I) and their pharmaceutically acceptable salts are described. Processes for their preparation, pharmaceutical compositions containing them, their use as medicaments and their use in the treatment of bacterial infections are also described.

  本文描述了化学式(I)的化合物及其药学上可接受的盐。还描述了制备它们的过程，包含它们的制药组合物，以及它们作为药物治疗细菌感染的用途。
• PYRIMIDINE DERIVATIVES FOR THE TREATMENT OF ABNORMAL CELL GROWTH
  申请人：Pfizer Products Inc.

  公开号：EP1578732A2

  公开（公告）日：2005-09-28
• [EN] COMPOUNDS FOR THE TREATMENT OF ABNORMAL CELL GROWTH<br/>[FR] COMPOSES POUR TRAITER LE DEVELOPPEMENT ANORMAL DE CELLULES
  申请人：PFIZER PROD INC

  公开号：WO2004056786A2

  公开（公告）日：2004-07-08

  The invention relates to compounds of the formula (1) and to pharmaceutically acceptable salts, prodrugs and solvates thereof, wherein R1, R2, R3, R4, R5, n, A and B are as defined herein. The invention also relates to methods of treating abnormal cell growth in mammals by administering the compounds of formula (1) and to pharmaceutical compositions for treating such disorders, which contain the compounds of formula (1). The invention also relates to methods of preparing the compounds of formula (1).
• [EN] HETEROCYCLIC DERIVATIVES AND METHODS OF USE THEREOF<br/>[FR] DÉRIVÉS HÉTÉROCYCLIQUES ET PROCÉDÉS D'UTILISATION ASSOCIÉS
  申请人：ASTRAZENECA AB

  公开号：WO2010038081A2

  公开（公告）日：2010-04-08

  Compounds of formula (I) and their pharmaceutically acceptable salts are described. Processes for their preparation, pharmaceutical compositions containing them, their use as medicaments and their use in the treatment of bacterial infections are also described.