N-(N-(3-(1H-indol-1-yl)phenyl)carbamimidoyl)-3,4,5-trimethoxybenzamide | 1263131-97-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: N-(N-(3-(1H-indol-1-yl)phenyl)carbamimidoyl)-3,4,5-trimethoxybenzamide
• 英文别名: N-[N'-(3-indol-1-ylphenyl)carbamimidoyl]-3,4,5-trimethoxybenzamide
• CAS: 1263131-97-0
• 化学式: C₂₅H₂₄N₄O₄
• 分子量: 444.49
• InChiKey: RXXFRHDYIHRLSF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  100
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-(3-nitrophenyl)-1H-indole 在 palladium 10% on activated carbon 、 甲酸铵 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 六甲基二硅氮烷 作用下， 以 异丙醇 、 丙酮 、 乙腈 为溶剂， 反应 6.0h， 生成 N-(N-(3-(1H-indol-1-yl)phenyl)carbamimidoyl)-3,4,5-trimethoxybenzamide
  参考文献：
  名称：

  Acylthiourea, Acylurea, and Acylguanidine Derivatives with Potent Hedgehog Inhibiting Activity

  摘要：

  The Smoothened (Smo) receptor is the major transducer of the Hedgehog (Hh) signaling pathway. On the basis of the structure of the acylthiourea Smo antagonist (MRT-10), a number of different series of analogous compounds were prepared by ligand-based structural optimization. The acylthioureas, originally identified as actives, were converted into the corresponding acylureas or acylguanidines. In each series, similar structural trends delivered potent compounds with IC50 values in the nanomolar range with respect to the inhibition of the Hh signaling pathway in various cell-based assays and of BODIPY-cyclopamine binding to human Smo. The similarity of their biological activities, in spite of discrete structural differences, may reveal the existence of hydrogen-bonding interactions between the ligands and the receptor pocket. Biological potency of compounds 61, 72, and 86 (MRT-83) were comparable to those of the clinical candidate GDC-0449. These findings suggest that these original molecules will help delineate Smo and Hh functions and can be developed as potential anticancer agents.

  DOI：

  10.1021/jm2013369

文献信息

• Acyl Guanidine Derivatives Modulating The Hedgehog Protein Signaling Pathway
  申请人：Ruat Martial

  公开号：US20120196865A1

  公开（公告）日：2012-08-02

  The present invention relates to acyl guanidine derivatives modulating the hedgehog protein signaling pathway to be used as drugs, in particular for treating diseases involving a tissue dysfunction associated with a deregulation of the hedgehog protein signaling pathway, as well as to pharmaceutical compositions containing same. The present invention also relates to novel acyl guanidine derivatives as such.

  本发明涉及酰基胍衍生物调节刺猬蛋白信号通路，用作药物，特别用于治疗涉及组织功能障碍的疾病，该功能障碍与刺猬蛋白信号通路的失调有关，以及含有同样物质的药物组合物。本发明还涉及作为新型酰基胍衍生物的物质。
• DERIVES D'ACYL-GUANIDINES MODULATEURS DE LA VOIE DE SIGNALISATION DES PROTEINES HEDGEHOG
  申请人：Université de Strasbourg

  公开号：EP2456754A1

  公开（公告）日：2012-05-30
• US8889678B2
  申请人：——

  公开号：US8889678B2

  公开（公告）日：2014-11-18
• [EN] ACYL GUANIDINE DERIVATIVES MODULATING THE HEDGEHOG PROTEIN SIGNALING PATHWAY<br/>[FR] DERIVES D'ACYL-GUANIDINES MODULATEURS DE LA VOIE DE SIGNALISATION DES PROTEINES HEDGEHOG
  申请人：CENTRE NAT RECH SCIENT

  公开号：WO2011010013A1

  公开（公告）日：2011-01-27

  La présente invention est relative à des dérivés d'acyl-guanidines modulateurs de la voie de signalisation des protéines Hedgehog à titre de médicaments, notamment pour le traitement de pathologies impliquant un dysfonctionnement tissulaire lié à une dérégulation de la voie de signalisation des protéines Hedgehog, ainsi qu'aux compositions pharmaceutiques les contenant. La présente invention concerne également de nouveaux dérivés d'acyl-guanidines en tant que tels.
• Acylthiourea, Acylurea, and Acylguanidine Derivatives with Potent Hedgehog Inhibiting Activity
  作者：Antonio Solinas、Hélène Faure、Hermine Roudaut、Elisabeth Traiffort、Angèle Schoenfelder、André Mann、Fabrizio Manetti、Maurizio Taddei、Martial Ruat

  DOI：10.1021/jm2013369

  日期：2012.2.23

  The Smoothened (Smo) receptor is the major transducer of the Hedgehog (Hh) signaling pathway. On the basis of the structure of the acylthiourea Smo antagonist (MRT-10), a number of different series of analogous compounds were prepared by ligand-based structural optimization. The acylthioureas, originally identified as actives, were converted into the corresponding acylureas or acylguanidines. In each series, similar structural trends delivered potent compounds with IC50 values in the nanomolar range with respect to the inhibition of the Hh signaling pathway in various cell-based assays and of BODIPY-cyclopamine binding to human Smo. The similarity of their biological activities, in spite of discrete structural differences, may reveal the existence of hydrogen-bonding interactions between the ligands and the receptor pocket. Biological potency of compounds 61, 72, and 86 (MRT-83) were comparable to those of the clinical candidate GDC-0449. These findings suggest that these original molecules will help delineate Smo and Hh functions and can be developed as potential anticancer agents.