2-bromo-N-(3-propionamidophenyl)benzamide | 423740-83-4

• 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: 2-bromo-N-(3-propionamidophenyl)benzamide
• 英文别名: 2-bromo-N-[3-(propanoylamino)phenyl]benzamide
• CAS: 423740-83-4
• 化学式: C₁₆H₁₅BrN₂O₂
• 分子量: 347.211
• InChiKey: MRHAVVLJBCSEMH-UHFFFAOYSA-N

物化性质

• 沸点：
  454.7±30.0 °C(Predicted)
• 密度：
  1.483±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2-bromo-N-(3-nitrophenyl)benzamide 在 盐酸 、 tin(II) chloride dihdyrate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-bromo-N-(3-propionamidophenyl)benzamide
  参考文献：
  名称：

  Characterization of Protease-Activated Receptor (PAR) ligands: Parmodulins are reversible allosteric inhibitors of PAR1-driven calcium mobilization in endothelial cells

  摘要：

  Several classes of ligands for Protease-Activated Receptors (PARs) have shown impressive anti-inflammatory and cytoprotective activities, including PAR2 antagonists and the PAR1-targeting parmodulins. In order to support medicinal chemistry studies with hundreds of compounds and to perform detailed mode-of-action studies, it became important to develop a reliable PAR assay that is operational with endothelial cells, which mediate the cytoprotective effects of interest. We report a detailed protocol for an intracellular calcium mobilization assay with adherent endothelial cells in multiwell plates that was used to study a number of known and new PAR1 and PAR2 ligands, including an alkynylated version of the PAR1 antagonist RWJ-58259 that is suitable for the preparation of tagged or conjugate compounds. Using the cell line EA. hy926, it was necessary to perform media exchanges with automated liquid handling equipment in order to obtain optimal and reproducible antagonist concentration-response curves. The assay is also suitable for study of PAR2 ligands; a peptide antagonist reported by Fairlie was synthesized and found to inhibit PAR2 in a manner consistent with reports using epithelial cells. The assay was used to confirm that vorapaxar acts as an irreversible antagonist of PAR1 in endothelium, and parmodulin 2 (ML161) and the related parmodulin RR-90 were found to inhibit PAR1 reversibly, in a manner consistent with negative allosteric modulation. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2018.04.016

文献信息

• The parmodulin NRD-21 is an allosteric inhibitor of PAR1 Gq signaling with improved anti-inflammatory activity and stability
  作者：Disha M. Gandhi、Ricardo Rosas、Eric Greve、Kaitlin Kentala、N'Guessan D.-R. Diby、Vladyslava A. Snyder、Allison Stephans、Teresa H.W. Yeung、Saravanan Subramaniam、Elliot DiMilo、Khia E. Kurtenbach、Leggy A. Arnold、Hartmut Weiler、Chris Dockendorff

  DOI：10.1016/j.bmc.2019.06.043

  日期：2019.9

  Novel analogs of the allosteric, biased PAR1 ligand ML161 (parmodulin 2, PM2) were prepared in order to identify potential anti-thrombotic and anti-inflammatory compounds of the parmodulin class with improved properties. Investigations of structure-activity relationships of the western portion of the 1,3-diaminobenzene scaffold were performed using an intracellular calcium mobilization assay with endothelial cells, and several heterocycles were identified that inhibited PAR1 at sub-micromolar concentrations. The oxazole NRD-21 was profiled in additional detail, and it was confirmed to act as a selective, reversible, negative allosteric modulator of PAR1. In addition to inhibiting human platelet aggregation, it showed superior anti-inflammatory activity to ML161 in a qPCR assay measuring the expression of tissue factor in response to the cytokine TNF-alpha in endothelial cells. Additionally, NRD-21 is much more plasma stable than ML161, and is a promising lead compound for the parmodulin class for anti-thrombotic and anti-inflammatory indications.
• US9422262B2
  申请人：——

  公开号：US9422262B2

  公开（公告）日：2016-08-23
• [EN] COMPOUNDS AND METHODS FOR TREATING DISEASES MEDIATED BY PROTEASE ACTIVATED RECEPTORS<br/>[FR] COMPOSÉS ET MÉTHODES DE TRAITEMENT DE MALADIES À MÉDIATION PAR DES RÉCEPTEURS ACTIVÉS PAR UNE PROTÉASE
  申请人：BROAD INST INC

  公开号：WO2012040636A2

  公开（公告）日：2012-03-29

  The invention relates to the use of a compound of Formula I for the treatment of protease-activated receptor mediated diseases by the administration of a compound of Formula I or a prodrug or metabolite thereof.
• Characterization of Protease-Activated Receptor (PAR) ligands: Parmodulins are reversible allosteric inhibitors of PAR1-driven calcium mobilization in endothelial cells
  作者：Disha M. Gandhi、Mark W. Majewski、Ricardo Rosas、Kaitlin Kentala、Trevor J. Foster、Eric Greve、Chris Dockendorff

  DOI：10.1016/j.bmc.2018.04.016

  日期：2018.5

  Several classes of ligands for Protease-Activated Receptors (PARs) have shown impressive anti-inflammatory and cytoprotective activities, including PAR2 antagonists and the PAR1-targeting parmodulins. In order to support medicinal chemistry studies with hundreds of compounds and to perform detailed mode-of-action studies, it became important to develop a reliable PAR assay that is operational with endothelial cells, which mediate the cytoprotective effects of interest. We report a detailed protocol for an intracellular calcium mobilization assay with adherent endothelial cells in multiwell plates that was used to study a number of known and new PAR1 and PAR2 ligands, including an alkynylated version of the PAR1 antagonist RWJ-58259 that is suitable for the preparation of tagged or conjugate compounds. Using the cell line EA. hy926, it was necessary to perform media exchanges with automated liquid handling equipment in order to obtain optimal and reproducible antagonist concentration-response curves. The assay is also suitable for study of PAR2 ligands; a peptide antagonist reported by Fairlie was synthesized and found to inhibit PAR2 in a manner consistent with reports using epithelial cells. The assay was used to confirm that vorapaxar acts as an irreversible antagonist of PAR1 in endothelium, and parmodulin 2 (ML161) and the related parmodulin RR-90 were found to inhibit PAR1 reversibly, in a manner consistent with negative allosteric modulation. (C) 2018 Elsevier Ltd. All rights reserved.