2-amino-4-chloro-6-(1-naphthylmethyl)-pyrrolo[2,3-d]pyrimidine | 651358-67-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-amino-4-chloro-6-(1-naphthylmethyl)-pyrrolo[2,3-d]pyrimidine
• 英文别名: 4-Chloro-6-[(naphthalen-1-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-2-amine；4-chloro-6-(naphthalen-1-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine
• CAS: 651358-67-7
• 化学式: C₁₇H₁₃ClN₄
• 分子量: 308.77
• InChiKey: MSZMUGNLUWQQMO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  67.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-氯-2-氟苯胺 、 2-amino-4-chloro-6-(1-naphthylmethyl)-pyrrolo[2,3-d]pyrimidine 在 盐酸 、 ammonium hydroxide 作用下， 以 水 、 异丙醇 为溶剂， 反应 12.0h， 以70%的产率得到N(4)-(4-chloro-2-fluorophenyl)-6-(1-naphthylmethyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine
  参考文献：
  名称：

  N4-Aryl-6-substitutedphenylmethyl-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines as receptor tyrosine kinase inhibitors

  摘要：

  Six novel N-4-substitutedphenyl-6-substitutedphenylmethy1-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines were synthesized as multiple receptor tyrosine kinase (RTK) inhibitors and antitumor agents. An improvement in the inhibitory potency against epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor 1 (VEGFR-1) and vascular endothelial growth factor receptor 2 (VEGFR-2) assays and in the A431 cellular proliferation assay was observed for compounds 8-13 over the previously reported 5-7. Three compounds (8.9 and 13) demonstrated potent, multiple RTK inhibition and were more potent or equipotent compared to the lead compounds 5 and 7 and the standard compounds. Compounds 10 and 12 showed potent inhibition of VEGFR-2 over EGFR, platelet-derived growth factor receptor-p (PDGFR-p) and VEGFR-1. The results indicate that the RIM inhibitory profile could be modulated with slight variations to the N-4-aryl-6-substitutedphenylmethyl-7H-Pyrrolo[2,3-d]wrimidine-2,4-diamino scaffold. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.058
• 作为产物：
  描述：

  萘-1-基乙酰氯 在 氢溴酸 、 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 78.0h， 生成 2-amino-4-chloro-6-(1-naphthylmethyl)-pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  抗血管生成和抗肿瘤药物。设计，合成和评估新型2-氨基-4-（3-溴苯胺基）-6-苄基取代的吡咯并[2,3-d]嘧啶作为受体酪氨酸激酶的抑制剂。

  摘要：

  包含酪氨酸激酶（RTK）的几种不同类别的生长因子受体直接或间接参与血管生成。抑制这些RTKs通过限制其生长和转移为肿瘤的治疗提供了新的范例。我们设计，合成和评估了11种新颖的2-氨基-4-（3-溴苯胺基）-6-取代的苄基吡咯并[2,3-d]嘧啶，这是一系列RTK抑制剂中的第一个。通过与2，6-二氨基-4-嘧啶酮进行环缩合反应，由合适的α-溴甲基苄基酮合成这些类似物，得到2-氨基-4-氧代-6-取代的苄基吡咯并[2，3-d]嘧啶。将4-位氯化，然后用3-溴苯胺置换，得到目标化合物。在某些情况下，吡咯并[2，在氯化和置换然后脱保护之前，对3-d]嘧啶进行保护。这些化合物被评估为血管内皮生长因子受体VEGFR-2（Flk-1，KDR）和VEGFR-1（Flt-1）的抑制剂。表皮生长因子受体（EGFR）; 和血小板衍生的生长因子受体-β（PDGFR-beta）。还评估了选定的化合物对培养物中A43

  DOI：

  10.1016/j.bmc.2003.08.034

文献信息

• N4-Aryl-6-substitutedphenylmethyl-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines as receptor tyrosine kinase inhibitors
  作者：Aleem Gangjee、Sonali Kurup、Michael A. Ihnat、Jessica E. Thorpe、Bryan Disch

  DOI：10.1016/j.bmc.2011.11.058

  日期：2012.1

  Six novel N-4-substitutedphenyl-6-substitutedphenylmethy1-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines were synthesized as multiple receptor tyrosine kinase (RTK) inhibitors and antitumor agents. An improvement in the inhibitory potency against epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor 1 (VEGFR-1) and vascular endothelial growth factor receptor 2 (VEGFR-2) assays and in the A431 cellular proliferation assay was observed for compounds 8-13 over the previously reported 5-7. Three compounds (8.9 and 13) demonstrated potent, multiple RTK inhibition and were more potent or equipotent compared to the lead compounds 5 and 7 and the standard compounds. Compounds 10 and 12 showed potent inhibition of VEGFR-2 over EGFR, platelet-derived growth factor receptor-p (PDGFR-p) and VEGFR-1. The results indicate that the RIM inhibitory profile could be modulated with slight variations to the N-4-aryl-6-substitutedphenylmethyl-7H-Pyrrolo[2,3-d]wrimidine-2,4-diamino scaffold. (C) 2011 Elsevier Ltd. All rights reserved.
• Antiangiogenic and antitumor agents
  作者：Aleem Gangjee、Jie Yang、Michael A. Ihnat、Shekhar Kamat

  DOI：10.1016/j.bmc.2003.08.034

  日期：2003.11

  containing tyrosine kinases (RTK) are directly or indirectly involved in angiogenesis. Inhibition of these RTKs has provided a new paradigm in the treatment of tumors by restricting their growth and metastasis. We have designed, synthesized and evaluated eleven novel 2-amino-4-(3-bromoanilino)-6-substituted benzyl pyrrolo[2,3-d]pyrimidines as the first in a series of RTK inhibitors. These analogues were

  包含酪氨酸激酶（RTK）的几种不同类别的生长因子受体直接或间接参与血管生成。抑制这些RTKs通过限制其生长和转移为肿瘤的治疗提供了新的范例。我们设计，合成和评估了11种新颖的2-氨基-4-（3-溴苯胺基）-6-取代的苄基吡咯并[2,3-d]嘧啶，这是一系列RTK抑制剂中的第一个。通过与2，6-二氨基-4-嘧啶酮进行环缩合反应，由合适的α-溴甲基苄基酮合成这些类似物，得到2-氨基-4-氧代-6-取代的苄基吡咯并[2，3-d]嘧啶。将4-位氯化，然后用3-溴苯胺置换，得到目标化合物。在某些情况下，吡咯并[2，在氯化和置换然后脱保护之前，对3-d]嘧啶进行保护。这些化合物被评估为血管内皮生长因子受体VEGFR-2（Flk-1，KDR）和VEGFR-1（Flt-1）的抑制剂。表皮生长因子受体（EGFR）; 和血小板衍生的生长因子受体-β（PDGFR-beta）。还评估了选定的化合物对培养物中A43