[4-(S)-(cyanophenyl)-4-methyl-2,5-dioxoimidazolidin-1-yl]acetic acid | 184426-81-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [4-(S)-(cyanophenyl)-4-methyl-2,5-dioxoimidazolidin-1-yl]acetic acid
• 英文别名: 2-((S)-4-(4-Cyanophenyl)-4-methyl-2,5-dioxoimidazolidin-1-yl)acetic acid；(S)-(4-(4-cyanophenyl)-4-methyl-2,5-dioxoimidazolidin-1-yl)acetic acid；((S)-4-(4-cyanophenyl)-4-methyl-2,5-dioxoimidazolidin-1-yl)acetic acid；2-[(4S)-4-(4-cyanophenyl)-4-methyl-2,5-dioxoimidazolidin-1-yl]acetic acid
• CAS: 184426-81-1
• 化学式: C₁₃H₁₁N₃O₄
• 分子量: 273.248
• InChiKey: BFLLTLLVSMDIMJ-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [4-(S)-(cyanophenyl)-4-methyl-2,5-dioxoimidazolidin-1-yl]acetic acid 在 盐酸 、 氨 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 24.0h， 生成 Carafiban
  参考文献：
  名称：

  基于乙内酰脲支架的口服活性非肽纤维蛋白原受体拮抗剂的发现。

  摘要：

  血小板纤维蛋白原受体（GP IIb / IIIa受体）的拮抗剂有望成为一种有前途的新型抗血栓药。纤维蛋白原与纤维蛋白原受体的结合取决于Arg-Gly-Asp-Ser（RGDS）四肽识别基序。RGDS导联的结构修饰导致发现了非肽RGD模拟GP IIb / IIIa拮抗剂44（S 1197）。化合物44以剂量依赖和可逆的方式抑制人和狗的血小板聚集以及125I-纤维蛋白原与ADP激活的人凝胶过滤的血小板和分离的GP IIb / IIIa的结合，K（i）的K（i）值为9 nM和0.17 nM ， 分别。使用QXP进行药效团映射的程序以及应用GRID / GOLPE方法进行的3D-QSAR分析产生了稳定的，相当可预测的模型，并揭示了对绑定非常重要的结构特征。在乙内酰脲核和C-末端的疏水取代均增加了对血纤蛋白原受体的亲和力。结晶乙酯前药48（HMR 1794）是一种口服活性抗血栓药，是治疗人类血栓性疾病的有前途的候选药物。

  DOI：

  10.1021/jm001068s
• 作为产物：
  描述：

  (S)-2-amino-2-(4-bromophenyl)-propionic acid ethyl ester 在 N-乙基吗啉 、 盐酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 9.5h， 生成 [4-(S)-(cyanophenyl)-4-methyl-2,5-dioxoimidazolidin-1-yl]acetic acid
  参考文献：
  名称：

  基于乙内酰脲支架的口服活性非肽纤维蛋白原受体拮抗剂的发现。

  摘要：

  血小板纤维蛋白原受体（GP IIb / IIIa受体）的拮抗剂有望成为一种有前途的新型抗血栓药。纤维蛋白原与纤维蛋白原受体的结合取决于Arg-Gly-Asp-Ser（RGDS）四肽识别基序。RGDS导联的结构修饰导致发现了非肽RGD模拟GP IIb / IIIa拮抗剂44（S 1197）。化合物44以剂量依赖和可逆的方式抑制人和狗的血小板聚集以及125I-纤维蛋白原与ADP激活的人凝胶过滤的血小板和分离的GP IIb / IIIa的结合，K（i）的K（i）值为9 nM和0.17 nM ， 分别。使用QXP进行药效团映射的程序以及应用GRID / GOLPE方法进行的3D-QSAR分析产生了稳定的，相当可预测的模型，并揭示了对绑定非常重要的结构特征。在乙内酰脲核和C-末端的疏水取代均增加了对血纤蛋白原受体的亲和力。结晶乙酯前药48（HMR 1794）是一种口服活性抗血栓药，是治疗人类血栓性疾病的有前途的候选药物。

  DOI：

  10.1021/jm001068s

文献信息

• Heterocyclic compounds, their preparation and their use as leucocyte
  申请人：Hoechst Marion Roussel Deutschland GmbH

  公开号：US06034238A1

  公开（公告）日：2000-03-07

  Compounds of the formula I, ##STR1## in which B, E, W, Y, Z, R, R.sup.2, R.sup.2a, R.sup.2b, R.sup.3, g and h have the meanings indicated in the specifications. The compounds of the formula I are valuable pharmaceutical active compounds, which are suitable, for example, for the therapy and prophylaxis of inflammatory disorders, for example of rheumatoid arthritis, or of allergic disorders. The compounds of the formula I are inhibitors of the adhesion and migration of leucocytes and/or antagonists of the adhesion receptor VLA-4 belonging to the integrins group. They are generally suitable for the therapy or prophylaxis of illnesses which are caused by an undesired extent of leucocyte adhesion and/or leucocyte migration or are associated therewith, or in which cell-cell or cell-matrix interactions which are based on interactions of VLA-4 receptors with their ligands play a part. The invention furthermore relates to processes for the preparation of the compounds of the formula I, their use in the therapy and prophylaxis of the disease states mentioned and pharmaceutical preparations which contain the compounds of the formula I.

  公式I的化合物，##STR1##其中B、E、W、Y、Z、R、R.sup.2、R.sup.2a、R.sup.2b、R.sup.3、g和h在规范中有所指示的含义。公式I的化合物是有价值的药用活性化合物，例如适用于炎症性疾病的治疗和预防，例如类风湿性关节炎或过敏性疾病。公式I的化合物是白细胞粘附和迁移的抑制剂和/或整合素群中属于VLA-4粘附受体的拮抗剂。它们通常适用于由于白细胞粘附和/或白细胞迁移的不良程度引起的疾病的治疗或预防，或与之相关的疾病，或者在其中基于VLA-4受体与其配体相互作用的细胞-细胞或细胞-基质相互作用起作用。此外，本发明还涉及制备公式I的化合物的方法，它们在治疗和预防所述疾病状态中的使用以及含有公式I的药物制剂。
• Novel heterocycles as inhibitors of leucocyte adhesion and as VLA-4 antagonists
  申请人：——

  公开号：US20020065391A1

  公开（公告）日：2002-05-30

  The present invention relates to compounds of the formula I 1 which are inhibitors of the adhesion and migration of leucocytes and/or antagonists of the adhesion receptor VLA-4 which belongs to the group of integrins. The invention also relates to processes for their preparation, to the use of compounds of the formula I for the treatment or prophylaxis of diseases which are caused by an undesired extent of leucocyte adhesion and/or leucocyte migration or which are associated therewith or in which cell-cell or cell-matrix interactions which are based on interactions of VLA-4 receptors with their ligands play a part, for example of inflammatory processes, of rheumatoid arthritis or of allergic disorders, and also to the use of compounds of the formula I for the production of pharmaceuticals for use in such diseases, and to pharmaceutical preparations which contain the compounds of the formula I.

  本发明涉及式I的化合物，该化合物是白细胞粘附和迁移的抑制剂和/或属于整合素群的粘附受体VLA-4的拮抗剂。该发明还涉及它们的制备方法，化合物式I用于治疗或预防由于白细胞粘附和/或白细胞迁移的不良程度引起的疾病，或与之相关的疾病，或基于VLA-4受体与其配体相互作用而发挥作用的细胞-细胞或细胞-基质相互作用的疾病，例如炎症过程、类风湿关节炎或过敏性疾病，以及化合物式I用于生产用于此类疾病的药物，以及含有化合物式I的药物制剂。
• Hydantoin compounds, salts thereof, processes for their preparation, and
  申请人：Hoechst Aktiengesellschaft

  公开号：US05939556A1

  公开（公告）日：1999-08-17

  The present invention relates to hydantoin derivatives of the formula I ##STR1## and which are intermediates for the preparation of pharmaceutical active compounds, their preparation and their use in the preparation of the active compounds.

  本发明涉及公式I的咪唑烷二酮衍生物，它们是制备药用活性化合物的中间体，以及它们的制备和在活性化合物的制备中的使用。
• 2,4-Substituted imidazolidine derivatives, their preparation, their use and pharmaceutical preparations comprising them
  申请人：Aventis Pharma Deutschland GmbH

  公开号：US06423712B1

  公开（公告）日：2002-07-23

  The present invention relates to imidazolidine compounds of the formula I, The compounds of the formula I are valuable pharmaceutical active compounds, which are suitable, for example, for the therapy and prophylaxis of inflammatory disorders, for example of rheumatoid arthritis, or of allergic disorders. The compounds of the formula I are inhibitors of the adhesion and migration of leucocytes and/or antagonists of the adhesion receptor VLA-4 belonging to the integrins group. They are generally suitable for the therapy or prophylaxis of illnesses which are caused by an undesired extent of leucocyte adhesion and/or leucocyte migration or are associated therewith, or in which cell-cell or cell-matrix interactions which are based on interactions of VLA-4 receptors with their ligands play a part. The invention furthermore relates to processes for the preparation of the compounds of the formula I, their use in the therapy and prophylaxis of the disease states mentioned and pharmaceutical preparations which contain compounds of the formula I.

  本发明涉及式I的咪唑啉化合物，式I的化合物是有价值的药用活性化合物，例如，适用于治疗和预防炎症性疾病，例如类风湿关节炎，或过敏性疾病。式I的化合物是白细胞粘附和迁移的抑制剂和/或整合素群中属于粘附受体VLA-4的拮抗剂。它们通常适用于治疗或预防由白细胞粘附和/或白细胞迁移的不良程度引起的疾病，或与之相关的疾病，或者在其中基于VLA-4受体与其配体相互作用的细胞-细胞或细胞-基质相互作用发挥作用。本发明还涉及制备式I化合物的方法，它们在治疗和预防上述疾病状态的使用以及含有式I化合物的制药制剂。
• Imidazolidine derivatives, their preparation, their use, and pharmaceutical preparations comprising them
  申请人：——

  公开号：US20030125565A1

  公开（公告）日：2003-07-03

  The present invention relates to novel imidazolidine derivatives of the formula I, 1 in which B, E, W, Z, R, R 0 , R 2 , R 3 , e and h have the meanings indicated in the application. The compounds of the formula I are valuable pharmaceutical active compounds, which are suitable, for example, for the therapy and prophylaxis of inflammatory disorders, for example of rheumatoid arthritis, or of allergic disorders. The compounds of the formula I are inhibitors of the adhesion and migration of leucocytes and/or antagonists of the adhesion receptor VLA-4 belonging to the integrins group. They are generally suitable for the therapy or prophylaxis of illnesses which are caused by an undesired extent of leucocyte adhesion and/or leucocyte migration or are associated therewith, or in which cell-cell or cell-matrix interactions which are based on interactions of VLA-4 receptors with their ligands play a part. The invention furthermore relates to processes for the preparation of the compounds of the formula I, their use in the therapy and prophylaxis of the disease states mentioned and pharmaceutical preparations which contain compounds of the formula I.

  本发明涉及公式I的新型咪唑啉衍生物，其中B、E、W、Z、R、R0、R2、R3、e和h在申请书中所示。公式I的化合物是有价值的药物活性化合物，适用于治疗和预防炎症性疾病，例如类风湿性关节炎或过敏性疾病。公式I的化合物是白细胞粘附和迁移的抑制剂和/或属于整合素组的粘附受体VLA-4的拮抗剂。它们通常适用于由白细胞粘附和/或白细胞迁移的不良程度引起或与之相关的疾病的治疗或预防，或者在其中基于VLA-4受体与其配体的相互作用的细胞-细胞或细胞-基质相互作用发挥作用。此外，本发明还涉及公式I化合物的制备方法，它们在上述疾病状态的治疗和预防中的应用以及含有公式I化合物的制药制剂。