4-((pyrimidin-2-ylamino)methyl)benzaldehyde | 405175-13-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-((pyrimidin-2-ylamino)methyl)benzaldehyde
• 英文别名: 4-[(pyrimidin-2-ylamino)methyl]benzaldehyde
• CAS: 405175-13-5
• 化学式: C₁₂H₁₁N₃O
• 分子量: 213.239
• InChiKey: BDTFWJDKZSVGIN-UHFFFAOYSA-N

物化性质

• 熔点：
  114-115 °C (decomp)
• 沸点：
  439.5±47.0 °C(Predicted)
• 密度：
  1.271±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  54.9
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  2-氟苯胺 、 4-((pyrimidin-2-ylamino)methyl)benzaldehyde 在 三乙酰氧基硼氢化钠 作用下， 以 1,2-二氯乙烷 为溶剂， 以57%的产率得到MSX-196
  参考文献：
  名称：

  双嘧啶胺：一类具有高特异性的新型趋化因子受体 4 型拮抗剂

  摘要：

  CXC 趋化因子受体 4 (CXCR4)/基质细胞衍生因子-1（SDF-1 或 CXCL12）相互作用和由此产生的细胞信号级联反应在转移和炎症中起关键作用。在先前发表的 CXCR4 拮抗剂5 (WZ811)的基础上，设计并合成了一系列新型非肽类抗 CXCR4 小分子以提高效力。根据大约5的结构-活性特征，发现了N , N '-(1, 4-亚苯基双(亚甲基)) dipyrimidin-2-amines 系列中更先进的化合物，并且显示出比5具有更高的 CXCR4 结合潜力和特异性。化合物26(508MCl) 是先导化合物，在三种体外试验中表现出亚纳摩尔的效力，包括竞争性结合、基质胶侵入和 Gα i环磷酸腺苷 (cAMP) 调节信号。此外，化合物26通过干扰三种小鼠模型中的 CXCR4 功能显示出有希望的效果：爪子炎症、Matrigel 栓塞血管生成和葡萄膜黑色素瘤微转移。这些数据表明，双嘧啶胺是独特的具有高效力和特异性的

  DOI：

  10.1021/jm100786g
• 作为产物：
  描述：

  [4-[(嘧啶-2-基氨基)甲基]苯基]甲醇 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 反应 1.17h， 以94%的产率得到4-((pyrimidin-2-ylamino)methyl)benzaldehyde
  参考文献：
  名称：

  双嘧啶胺：一类具有高特异性的新型趋化因子受体 4 型拮抗剂

  摘要：

  CXC 趋化因子受体 4 (CXCR4)/基质细胞衍生因子-1（SDF-1 或 CXCL12）相互作用和由此产生的细胞信号级联反应在转移和炎症中起关键作用。在先前发表的 CXCR4 拮抗剂5 (WZ811)的基础上，设计并合成了一系列新型非肽类抗 CXCR4 小分子以提高效力。根据大约5的结构-活性特征，发现了N , N '-(1, 4-亚苯基双(亚甲基)) dipyrimidin-2-amines 系列中更先进的化合物，并且显示出比5具有更高的 CXCR4 结合潜力和特异性。化合物26(508MCl) 是先导化合物，在三种体外试验中表现出亚纳摩尔的效力，包括竞争性结合、基质胶侵入和 Gα i环磷酸腺苷 (cAMP) 调节信号。此外，化合物26通过干扰三种小鼠模型中的 CXCR4 功能显示出有希望的效果：爪子炎症、Matrigel 栓塞血管生成和葡萄膜黑色素瘤微转移。这些数据表明，双嘧啶胺是独特的具有高效力和特异性的

  DOI：

  10.1021/jm100786g

文献信息

• Chemokine receptor binding heterocyclic compounds
  申请人：——

  公开号：US20040220207A1

  公开（公告）日：2004-11-04

  Novel compounds that are useful for targeting chemokine receptors are disclosed. These compounds are complex tertiary amines.

  本发明揭示了用于靶向趋化因子受体的新化合物。这些化合物是复杂的三级胺。
• Chemokine receptor modulators
  申请人：Clark Michael P.

  公开号：US20080293711A1

  公开（公告）日：2008-11-27

  The invention provides compounds of Formula (I) and pharmaceutical compositions comprising compounds of Formula (I). These compounds are useful treating or preventing HIV infections, and in treating proliferative disorders such as inhibiting the metastasis of various cancers.

  本发明提供了化合物(I)及包含化合物(I)的药物组合物。这些化合物可用于治疗或预防HIV感染，并用于治疗增殖性疾病，如抑制各种癌症的转移。
• WO2008/112156
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis and evaluation of an 18 F-labeled pyrimidine-pyridine amine for targeting CXCR4 receptors in gliomas
  作者：Dustin Wayne Demoin、Masahiro Shindo、Hanwen Zhang、Kimberly J. Edwards、Inna Serganova、Naga Vara Kishore Pillarsetty、Jason S. Lewis、Ronald G. Blasberg

  DOI：10.1016/j.nucmedbio.2016.05.005

  日期：2016.10

  Introduction: Chemokine receptor-4 (CXCR4, fusin, CD184) is expressed on several tissues involved in immune regulation and is upregulated in many diseases including malignant gliomas. A radiolabeled small molecule that readily crosses the blood-brain barrier can aid in identifying CXCR4-expressing gliomas and monitoring CXCR4-targeted therapy. In the current work, we have synthesized and evaluated an [F-18]-labeled small molecule based on a pyrimidine-pyridine amine for its ability to target CXCR4.Experimental: The nonradioactive standards and the nitro precursor used in this study were prepared using established methods. An HPLC method was developed to separate the nitro-precursor from the nonradioactive standard and radioactive product The nitro-precursor was radiolabeled with F-18 under inert, anhydrous conditions using the [F-18]-kryptofix 22.2 complex to form the desired N-(4-(((6-[F-18]fluoropyridin-2-yl)amino)methyl)benzyl)pyrimidin-2-amine [F-18]-3). The purified radiolabeled compound was used in serum stability, partition coefficient, cellular uptake, and in vivo cancer targeting studies.Results: [F-18]-3 was synthesized in 4-10% decay-corrected yield (to start of synthesis). [F-18]-3 (t(R) approximate to 27 min) was separated from the precursor (t(R) approximate to 30 min) using a pentafluorophenyl column with an isocratic solvent system. [F-18]-3 displayed acceptable serum stability over 2 h. The amount of [F-18]-3 bound to the plasma proteins was determined to be > 97%. The partition coefficient (LogD(7.4)) is 1.4 +/- 0.5. Competitive in vitro inhibition indicated 3 does not inhibit uptake of Ga-67-pentixafor. Cell culture media incubation and ex vivo urine analysis indicate rapid metabolism of [F-18]-3 into hydrophilic metabolites. Thus, in vitro uptake of [F-18]-3 in CXCR4 overexpressing U87 cells (U87 CXCR4) and U87 WT indicated no specific binding. In vivo studies in mice bearing U87 CXCR4 and U87 WT tumors on the left and right shoulders were carried out using [F-18]-3 and Ga-68-pentixafor on consecutive days. The CXCR4 positive tumor was clearly visualized in the PET study using Ga-68-pentixafor, but not with [F-18]-3.Conclusions: We have successfully synthesized both a radiolabeled analog to previously reported CXCR4-targeting molecules and a nitro precursor. Our in vitro and in vivo studies indicate that [F-18]-3 is rapidly metabolized and, therefore, does not target CXCR4-expressing tumors. Optimization of the structure to improve the in vivo (and in vitro) stability, binding, and solubility could lead to an appropriate CXCR4-targeted radiodiagnositic molecule. (C) 2016 Elsevier Inc. All rights reserved.
• CHEMOKINE RECEPTOR BINDING HETEROCYCLIC COMPOUNDS
  申请人：ANORMED INC.

  公开号：EP1317445B1

  公开（公告）日：2009-03-11