N-(3-benzamidophenylcarbamothioyl)-7-methoxybenzo[d][1,3]dioxole-5-carboxamide | 1192927-96-0

• 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: N-(3-benzamidophenylcarbamothioyl)-7-methoxybenzo[d][1,3]dioxole-5-carboxamide
• 英文别名: N-[[[3-(benzoylamino)phenyl]amino]thioxomethyl]-3,4-methylenedioxy-5-methoxy-benzamide；N-[(3-benzamidophenyl)carbamothioyl]-7-methoxy-1,3-benzodioxole-5-carboxamide
• CAS: 1192927-96-0
• 化学式: C₂₃H₁₉N₃O₅S
• 分子量: 449.487
• InChiKey: VEIPJJWEVPDZPO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  130
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(3-benzamidophenylcarbamothioyl)-7-methoxybenzo[d][1,3]dioxole-5-carboxamide 在 copper(l) chloride 、 sodium hydroxide 作用下， 以 乙腈 为溶剂， 120.0 ℃ 、344.75 kPa 条件下， 反应 0.1h， 以37%的产率得到N-(3-benzamidophenylcarbamoyl)-7-methoxybenzo[d][1,3]dioxole-5-carboxamide
  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
• 作为产物：
  描述：

  7-甲氧基-1,3-苯并二氧化物-5-羧酸 在 草酰氯 作用下， 以 丙酮 为溶剂， 反应 1.33h， 生成 N-(3-benzamidophenylcarbamothioyl)-7-methoxybenzo[d][1,3]dioxole-5-carboxamide
  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

• N-Acylthiourea and N-Acylurea Inhibitors of the Hedgehog Protein Signalling Pathway
  申请人：Ruat Martial

  公开号：US20110275663A1

  公开（公告）日：2011-11-10

  The present invention relates to the use of acylthiourea or acylurea derivatives for the treatment of pathologies involving a tissue dysfunction associated with a deregulation of the Hedgehog protein signalling pathway, and also to novel acylthiourea or acylurea derivatives as such, to their use as a medicinal product, and to pharmaceutical compositions containing them.

  本发明涉及使用酰基硫脲或酰基脲衍生物治疗涉及组织功能障碍的病理情况，该功能障碍与Hedgehog蛋白信号通路的失调有关，并且涉及作为药物产品的新型酰基硫脲或酰基脲衍生物，它们的用途以及含有它们的药物组成物。
• N-ACYLTHIOUREES ET N-ACYLUREES INHIBITEURS DE LA VOIE DE SIGNALISATION DES PROTEINES HEDGEHOG
  申请人：Centre National de la Recherche Scientifique

  公开号：EP2291352A2

  公开（公告）日：2011-03-09
• US9073835B2
  申请人：——

  公开号：US9073835B2

  公开（公告）日：2015-07-07
• [EN] N-ACYLTHIOUREA AND N-ACYLUREA INHIBITORS OF THE HEDGEHOG PROTEIN SIGNALLING PATHWAY<br/>[FR] N-ACYLTHIOUREES ET N-ACYLUREES INHIBITEURS DE LA VOIE DE SIGNALISATION DES PROTEINES HEDGEHOG
  申请人：CENTRE NAT RECH SCIENT

  公开号：WO2009130422A2

  公开（公告）日：2009-10-29

  La présente invention est relative à l'utilisation de dérivés d'acyl- thiourées ou d'acyl-urées pour le traitement de pathologies impliquant un dysfonctionnement tissulaire lié à une dérégulation de la voie de signalisation des protéines Hedgehog, ainsi qu'à de nouveaux dérivés d'acyl-thiourées ou d'acyl-urées en tant que tels, à leur utilisation comme médicament, et aux compositions pharmaceutiques les contenant.
• 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.