N-[3-(5-甲基吡咯并[3,2-d]嘧啶-4-基)氧苯基]苯甲酰胺 | 919280-32-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-[3-(5-甲基吡咯并[3,2-d]嘧啶-4-基)氧苯基]苯甲酰胺
• 英文名称: N-{3-[(5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-yl)oxy]phenyl}-benzamide
• 英文别名: N-{3-[(5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-yl)oxy]phenyl}benzamide；N-[3-(5-methylpyrrolo[3,2-d]pyrimidin-4-yl)oxyphenyl]benzamide
• CAS: 919280-32-3
• 化学式: C₂₀H₁₆N₄O₂
• 分子量: 344.373
• InChiKey: FGMPNGRIDAWFLE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  69
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-[(5-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-yl)oxy]aniline 、 苯甲酰氯 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 以44%的产率得到N-[3-(5-甲基吡咯并[3,2-d]嘧啶-4-基)氧苯基]苯甲酰胺
  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

文献信息

• Fused Heterocyclic Derivatives and Use Thereof
  申请人：Imamura Shinichi

  公开号：US20090137580A1

  公开（公告）日：2009-05-28

  The present invention provides a fused heterocyclic derivative showing a potent kinase inhibitory activity and use thereof. A compound represented by the formula: wherein ring A is an optionally substituted pyrrole ring, X is an optionally substituted CH, Y is an optionally substituted CH or nitrogen atom, Z is an optionally substituted divalent hydrocarbon group or optionally substituted divalent heterocyclic group, T is a single bond or an optionally substituted C 1-3 alkylene group, and U is an optionally substituted amido group, an optionally substituted sulfonamido group, an optionally substituted ureido group, an optionally substituted carbamoyl group or an optionally substituted thioureido group, or a salt thereof, and a pharmaceutical agent containing the compound or a prodrug thereof, which is a kinase (VEGFR, VEGFR2, PDGFR, TIE2) inhibitor, an angiogenesis inhibitor, an agent for the prophylaxis or treatment of cancer, an agent for inhibiting growth of cancer or an agent for suppressing metastasis of cancer.

  本发明提供了一种融合的杂环衍生物，具有强大的激酶抑制活性及其用途。该化合物由以下公式表示： 其中，环A是可选的取代吡咯环，X是可选的取代的CH，Y是可选的取代的CH或氮原子，Z是可选的取代的二价碳氢基团或可选的取代的二价杂环基团，T是单键或可选的取代的C1-3烷基团，U是可选的取代的酰胺基团、可选的取代的磺酰胺基团、可选的取代的脲基团、可选的取代的氨基甲酰基团或可选的取代的硫脲基团，或其盐，以及含有该化合物或其前药的药物制剂，该制剂是激酶(VEGFR、VEGFR2、PDGFR、TIE2)抑制剂、血管生成抑制剂、预防或治疗癌症的药物、抑制癌症生长的药物或抑制癌症转移的药物。
• FUSED HETEROCYCLIC DERIVATIVES AND USE THEREOF
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1904498A1

  公开（公告）日：2008-04-02
• [EN] FUSED HETEROCYCLIC DERIVATIVES AND USE THEREOF<br/>[FR] DÉRIVÉS HÉTÉROCYCLIQUES FONDUS ET LEUR UTILISATION
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2007004749A1

  公开（公告）日：2007-01-11

  [EN] The present invention provides a fused heterocyclic derivative showing a potent kinase inhibitory activity and use thereof. A compound represented by the formula: (I) wherein ring A is an optionally substituted pyrrole ring, X is an optionally substituted CH, Y is an optionally substituted CH or nitrogen atom, Z is an optionally substituted divalent hydrocarbon group or optionally substituted divalent heterocyclic group, T is a single bond or an optionally substituted C_1-3 alkylene group, and U is an optionally substituted amido group, an optionally substituted sulfonamido group, an optionally substituted ureido group, an optionally substituted carbamoyl group or an optionally substituted thioureido group, or a salt thereof, and a pharmaceutical agent containing the compound or a prodrug thereof, which is a kinase (VEGFR, VEGFR2, PDGFR, TIE2) inhibitor, an angiogenesis inhibitor, an agent for the prophylaxis or treatment of cancer, an agent for inhibiting growth of cancer or an agent for suppressing metastasis of cancer.
  [FR] La présente invention fournit un dérivé hétérocyclique fondu présentant une puissante activité inhibitrice de kinase et son utilisation. Un composé représenté par la formule générale : (I) dans laquelle le cycle A est un cycle pyrrole éventuellement substitué, X est un CH éventuellement substitué, Y est un CH ou un atome d'azote éventuellement substitué, Z est un groupe hydrocarboné divalent éventuellement substitué ou un groupe hétérocyclique divalent éventuellement substitué, T est une liaison simple ou un groupe C_1-3 alkylène éventuellement substitué et U est un groupe amido éventuellement substitué, un groupe sulfonamido éventuellement substitué, un groupe uréido éventuellement substitué, un groupe carbamoyle éventuellement substitué ou un groupe thiouréido éventuellement substitué, ou un de leurs sels, et un agent pharmaceutique contenant le composé ou un promédicament de celui-ci, qui est un inhibiteur de kinase (VEGFR, VEGFR2, PDGFR, TIE2), un inhibiteur d'angiogenèse, un agent pour la prophylaxie ou le traitement d'un cancer, un agent pour inhiber la croissance d'un cancer ou un agent pour éliminer les métastases cancéreuses.
• 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
  作者：Yuya Oguro、Naoki Miyamoto、Kengo Okada、Terufumi Takagi、Hidehisa Iwata、Yoshiko Awazu、Hiroshi Miki、Akira Hori、Keiji Kamiyama、Shinichi Imamura

  DOI：10.1016/j.bmc.2010.08.017

  日期：2010.10.15

  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.