4-carbamothioyl-N-[2-[(4-methoxybenzoyl)amino]phenyl]benzamide | 239120-44-6

• 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: 4-carbamothioyl-N-[2-[(4-methoxybenzoyl)amino]phenyl]benzamide
• CAS: 239120-44-6
• 化学式: C₂₂H₁₉N₃O₃S
• 分子量: 405.477
• InChiKey: PBAHTRPLESJKAX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  126
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-carbamothioyl-N-[2-[(4-methoxybenzoyl)amino]phenyl]benzamide 在 ammonium acetate 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 14.0h， 生成 4-carbamimidoyl-N-[2-[(4-methoxybenzoyl)amino]phenyl]benzamide
  参考文献：
  名称：

  Structure-Based Design of Potent, Amidine-Derived Inhibitors of Factor Xa:  Evaluation of Selectivity, Anticoagulant Activity, and Antithrombotic Activity

  摘要：

  To enhance the potency of 1,2-dibenzamidobenzene-derived inhibitors of factor Xa (fXa), an amidine substituent was incorporated on one of the benzoyl side chains to interact with Asp189 in the S1 specificity pocket. Lead molecule 1 was docked into the active site of Ma to facilitate inhibitor design. Subsequently, iterative SAR studies and molecular modeling led to a 1000-fold increase in Ma affinity and a refined model of the new inhibitors in the Ma active site. Strong support for the computational model was achieved through the acquisition of an X-ray crystal structure using thrombin as a surrogate protein. The amidines in this series show high levels of selectivity for the inhibition of Ma relative to other trypsin-like serine proteases. Furthermore, the Ma affinity of compounds in this series (K-ass = 50-500 x 10(6) L/mol) translates effectively into both anticoagulant activity in vitro and antithrombotic activity in vivo.

  DOI：

  10.1021/jm9903287
• 作为产物：
  描述：

  N¹-(4-cyanobenzoyl)-N²-(4-methoxybenzoyl)-1,2-benzenediamine 在 吡啶 、 硫化氢 、 三乙胺 作用下， 反应 48.0h， 生成 4-carbamothioyl-N-[2-[(4-methoxybenzoyl)amino]phenyl]benzamide
  参考文献：
  名称：

  Structure-Based Design of Potent, Amidine-Derived Inhibitors of Factor Xa:  Evaluation of Selectivity, Anticoagulant Activity, and Antithrombotic Activity

  摘要：

  To enhance the potency of 1,2-dibenzamidobenzene-derived inhibitors of factor Xa (fXa), an amidine substituent was incorporated on one of the benzoyl side chains to interact with Asp189 in the S1 specificity pocket. Lead molecule 1 was docked into the active site of Ma to facilitate inhibitor design. Subsequently, iterative SAR studies and molecular modeling led to a 1000-fold increase in Ma affinity and a refined model of the new inhibitors in the Ma active site. Strong support for the computational model was achieved through the acquisition of an X-ray crystal structure using thrombin as a surrogate protein. The amidines in this series show high levels of selectivity for the inhibition of Ma relative to other trypsin-like serine proteases. Furthermore, the Ma affinity of compounds in this series (K-ass = 50-500 x 10(6) L/mol) translates effectively into both anticoagulant activity in vitro and antithrombotic activity in vivo.

  DOI：

  10.1021/jm9903287

文献信息

• Neue Thiobenzamide, Verfahren zu ihrer Herstellung sowie diese enthaltende Arzneimittel
  申请人：Roche Diagnostics GmbH

  公开号：EP0937711A1

  公开（公告）日：1999-08-25

  Die Erfindung betrifft neue Thiobenzamide der allgemeinen Formel I in der R1 bis R4, die in der Beschreibung angegebene Bedeutung haben, sowie deren Hydrate, Solvate und physiologisch verträgliche Salze, optisch aktive Formen, Racemate und Diastereomerengemische, Verfahren zu ihrer Herstellung sowie Arzneimittel, die diese Verbindungen enthalten zur Behandlung thromboembolischer Erkrankungen.

  本发明涉及通式 I 的新硫代苯甲酰胺。 中 R1 至 R4 的含义，以及它们的水合物、溶解物和生理上可耐受的盐、光学活性形式、外消旋体和非对映异构体混合物、它们的制备工艺和含有这些化合物的治疗血栓栓塞性疾病的药物。
• [EN] NOVEL THIOBENZAMIDES<br/>[FR] NOUVEAUX THIOBENZAMIDES
  申请人：ROCHE DIAGNOSTICS GMBH

  公开号：WO1999042439A1

  公开（公告）日：1999-08-26

  (EN) The invention relates to novel thiobenzamides of general formula (I) in which R1 to R4 have the meaning indicated in the description, and their hydrates, solvates and physiologically tolerable salts, optically active forms, racemates and diastereomer mixtures, processes for their preparation and medicaments which comprise these compounds, for the treatment of thromboembolic disorders.(FR) L'invention porte sur de nouveaux thiobenzamides de la formule générale (I) dans laquelle R1 à R4 sont tels que définis dans la demande, ainsi que sur leurs hydrates, leurs solvates et leurs sels physiologiquement tolérables, sur leurs formes optiquement actives, les composés racémiques et les mélanges diastéréomères, leurs procédés de préparation et les médicaments comprenant ces composés qui sont destinés à être utilisés dans le traitement des désordres thromboemboliques.
• Structure-Based Design of Potent, Amidine-Derived Inhibitors of Factor Xa:  Evaluation of Selectivity, Anticoagulant Activity, and Antithrombotic Activity
  作者：Michael R. Wiley、Leonard C. Weir、Steven Briggs、Nancy A. Bryan、John Buben、Charles Campbell、Nickolay Y. Chirgadze、Richard C. Conrad、Trelia J. Craft、James V. Ficorilli、Jeffry B. Franciskovich、Larry L. Froelich、Donetta S. Gifford-Moore、Theodore Goodson、David K. Herron、Valentine J. Klimkowski、Kenneth D. Kurz、Jeffery A. Kyle、John J. Masters、Andrew M. Ratz、Guy Milot、Robert T. Shuman、Tommy Smith、Gerald F. Smith、Ann Louise Tebbe、Jennifer M. Tinsley、Richard D. Towner、Alexander Wilson、Ying K. Yee

  DOI：10.1021/jm9903287

  日期：2000.3.1

  To enhance the potency of 1,2-dibenzamidobenzene-derived inhibitors of factor Xa (fXa), an amidine substituent was incorporated on one of the benzoyl side chains to interact with Asp189 in the S1 specificity pocket. Lead molecule 1 was docked into the active site of Ma to facilitate inhibitor design. Subsequently, iterative SAR studies and molecular modeling led to a 1000-fold increase in Ma affinity and a refined model of the new inhibitors in the Ma active site. Strong support for the computational model was achieved through the acquisition of an X-ray crystal structure using thrombin as a surrogate protein. The amidines in this series show high levels of selectivity for the inhibition of Ma relative to other trypsin-like serine proteases. Furthermore, the Ma affinity of compounds in this series (K-ass = 50-500 x 10(6) L/mol) translates effectively into both anticoagulant activity in vitro and antithrombotic activity in vivo.