N-(5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-yl)benzene-1,4-diamine | 1255948-54-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: N-(5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-yl)benzene-1,4-diamine
• CAS: 1255948-54-9
• 化学式: C₁₃H₁₃N₅
• 分子量: 239.28
• InChiKey: ACHZUVILMRTULL-UHFFFAOYSA-N

反应信息

• 作为反应物：
  描述：

  N-(5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-yl)benzene-1,4-diamine 、 异氰酸苯酯 以 四氢呋喃 为溶剂， 反应 15.0h， 以13%的产率得到1-{4-[(5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-yl)amino]-phenyl}-3-phenylurea
  参考文献：
  名称：

  Design, synthesis, and evaluation of 5-methyl-4-phenoxy-5H-pyrrolo[3,2-d]pyrimidine derivatives: Novel VEGFR2 kinase inhibitors binding to inactive kinase conformation

  摘要：

  We synthesized a series of pyrrolo[3,2-d] pyrimidine derivatives and evaluated their application as type-II inhibitors of vascular endothelial growth factor receptor 2 (VEGFR2) kinase. Incorporation of a diphenylurea moiety at the C4-position of the pyrrolo[3,2-d] pyrimidine core via an oxygen linker resulted in compounds that were potent inhibitors of VEGFR2 kinase. Of these derivatives, compound 20d showed the strongest inhibition of VEGF-stimulated proliferation of human umbilical vein endothelial cells (HUVEC). The co-crystal structure of 20d and VEGFR2 revealed that 20d binds to the inactive form of VEGFR2. Further studies indicated that 20d inhibited VEGFR2 kinase with slow dissociation kinetics and also inhibited PDGFR and Tie-2 kinases. Oral administration of the hydrochloride salt of 20d at 3 mg/kg/day showed potent inhibition of tumor growth in a DU145 human prostate cancer cell xenograft nude mouse model. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.08.017
• 作为产物：
  描述：

  在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以867 mg的产率得到N-(5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-yl)benzene-1,4-diamine
  参考文献：
  名称：

  Design, synthesis, and evaluation of 5-methyl-4-phenoxy-5H-pyrrolo[3,2-d]pyrimidine derivatives: Novel VEGFR2 kinase inhibitors binding to inactive kinase conformation

  摘要：

  We synthesized a series of pyrrolo[3,2-d] pyrimidine derivatives and evaluated their application as type-II inhibitors of vascular endothelial growth factor receptor 2 (VEGFR2) kinase. Incorporation of a diphenylurea moiety at the C4-position of the pyrrolo[3,2-d] pyrimidine core via an oxygen linker resulted in compounds that were potent inhibitors of VEGFR2 kinase. Of these derivatives, compound 20d showed the strongest inhibition of VEGF-stimulated proliferation of human umbilical vein endothelial cells (HUVEC). The co-crystal structure of 20d and VEGFR2 revealed that 20d binds to the inactive form of VEGFR2. Further studies indicated that 20d inhibited VEGFR2 kinase with slow dissociation kinetics and also inhibited PDGFR and Tie-2 kinases. Oral administration of the hydrochloride salt of 20d at 3 mg/kg/day showed potent inhibition of tumor growth in a DU145 human prostate cancer cell xenograft nude mouse model. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.08.017