(2S)-1-[3-(1-t-butoxycarbonyl-3-methylbutyl)ureido]cyclohexane-1-carboxylic acid methyl ester | 306768-96-7

• 英文名称: (2S)-1-[3-(1-t-butoxycarbonyl-3-methylbutyl)ureido]cyclohexane-1-carboxylic acid methyl ester
• 英文别名: methyl 1-(3-((S)-1-tert-butoxycarbonyl-3-methylbutyl)ureido)cyclohexanecarboxylate；methyl 1-[[(2S)-4-methyl-1-[(2-methylpropan-2-yl)oxy]-1-oxopentan-2-yl]carbamoylamino]cyclohexane-1-carboxylate
• CAS: 306768-96-7
• 化学式: C₁₉H₃₄N₂O₅
• 分子量: 370.489
• InChiKey: OUNZHMCWUAEXSY-AWEZNQCLSA-N

物化性质

• 沸点：
  498.4±38.0 °C(Predicted)
• 密度：
  1.08±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  93.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S)-1-[3-(1-t-butoxycarbonyl-3-methylbutyl)ureido]cyclohexane-1-carboxylic acid methyl ester 在 盐酸 、 正丁基锂 、 O-[(ethoxycarbonyl)cyanomethyleneamino]-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 (3S)-(3,4-dimethoxyphenyl)-3-[(2S)-{2,4-dioxo-1-[4-(3-phenylureido)benzyl]-1,3-diazaspiro[4.5]dec-3-yl}-4-methylpentanoylamino]propionic acid tert-butyl ester
  参考文献：
  名称：

  Aromatic β-Amino Acids as Asp-Phg Mimics in LDV Derived VLA-4 Antagonists­

  摘要：

  芳香性 β-氨基酸酯 2a-h 通过 Radionow 反应或基于 Davis 描述的方法制备成外消旋形式和手性纯形式，并作为模拟 LDV 衍生的 VLA-4 拮抗剂中的 Asp-Phg C 末端。作为一种有前景的 β-氨基酸酯，11 被鉴定并用以合成高效力的 VLA-4 拮抗剂 S9059，其在细胞粘附试验中的 IC50 值为 1.6 nM。

  DOI：

  10.1055/s-2002-34389
• 作为产物：
  描述：

  1-氨基-1-环己基甲酸 在 氯化亚砜 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 (2S)-1-[3-(1-t-butoxycarbonyl-3-methylbutyl)ureido]cyclohexane-1-carboxylic acid methyl ester
  参考文献：
  名称：

  Aromatic β-Amino Acids as Asp-Phg Mimics in LDV Derived VLA-4 Antagonists­

  摘要：

  芳香性 β-氨基酸酯 2a-h 通过 Radionow 反应或基于 Davis 描述的方法制备成外消旋形式和手性纯形式，并作为模拟 LDV 衍生的 VLA-4 拮抗剂中的 Asp-Phg C 末端。作为一种有前景的 β-氨基酸酯，11 被鉴定并用以合成高效力的 VLA-4 拮抗剂 S9059，其在细胞粘附试验中的 IC50 值为 1.6 nM。

  DOI：

  10.1055/s-2002-34389

文献信息

• Spiroimidazolidine derivatives, their preparation, their use and pharmaceutical preparations formed therefrom
  申请人：Aventis Pharma Deutschland GmbH

  公开号：US06399643B1

  公开（公告）日：2002-06-04

  The present invention relates to spiroimidazolidine derivatives of the formula I in which E, V, W, X, R1 and R2 have the meanings indicated in the claims. The compounds of the formula I are valuable pharmaceutical active compounds which are suitable, for example, for the therapy and prophylaxis of inflammatory disorders, such as, for example, rheumatoid arthritis, or allergic disorders. The compounds of the formula I are also inhibitors of the adhesion and migration of leukocytes and/or antagonists of the adhesion receptor VLA-4 belonging to the integrins group. They are generally suitable for the therapy and prophylaxis of illnesses which are caused by an undesired extent of leukocyte adhesion and/or leukocyte 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 also relates to processes for the preparation of the compounds of the formula I, pharmaceutical preparations which contain compounds of the formula I, and methods for treating these disorders.

  本发明涉及式I的螺环咪唑啉衍生物，其中E、V、W、X、R1和R2具有索引中指示的含义。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，如风湿性关节炎或过敏性疾病。式I的化合物还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。它们通常适用于治疗和预防由白细胞粘附和/或白细胞迁移不受欢迎的程度引起的疾病，或与之相关的疾病，或在其中基于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的疾病。该发明还涉及制备式I的化合物的方法、含有式I的药物制剂以及治疗这些疾病的方法。
• SPIROIMIDAZOLIDINE DERIVATIVES, THEIR PREPARATION, THEIR USE AND PHARMACEUTICAL PREPARATIONS COMPRISING THEM
  申请人：Aventis Pharma Deutschland GmbH

  公开号：EP1183241A1

  公开（公告）日：2002-03-06
• US6399643B1
  申请人：——

  公开号：US6399643B1

  公开（公告）日：2002-06-04
• [EN] SPIROIMIDAZOLIDINE DERIVATIVES, THEIR PREPARATION, THEIR USE AND PHARMACEUTICAL PREPARATIONS COMPRISING THEM<br/>[FR] DERIVES DE SPIROIMIDAZOLIDINE, PREPARATION ET UTILISATION DE CES DERIVES ET PREPARATION PHARMACEUTIQUES A BASE DE CES DERIVES.
  申请人：AVENTIS PHARMA GMBH

  公开号：WO2000069831A1

  公开（公告）日：2000-11-23

  The present invention relates to spiroimidazolidine derivatives of formula (I) in which E, V, W, X, R?1 and R2¿ have the meanings indicated in the claims. The compounds of 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 formula (I) are inhibitors of the adhesion and migration of leukocytes and/or antagonists of the adhesion receptor VLA-4 belonging to the integrins group. They are generally suitable for the therapy and prophylaxis of illnesses which are caused by an undesired extent of leukocyte adhesion and/or leukocyte 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 formula (I), their use and pharmaceutical preparations which contain compounds of formula (I).