(R)-4-(tert-butoxy)-4-oxo-2-(thiophen-2-yl)butanoic acid | 207120-62-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (R)-4-(tert-butoxy)-4-oxo-2-(thiophen-2-yl)butanoic acid
• 英文别名: 2(R)-thien-2-yl-succinic acid 4-t-butyl ester；(2R)-4-[(2-methylpropan-2-yl)oxy]-4-oxo-2-thiophen-2-ylbutanoic acid
• CAS: 207120-62-5
• 化学式: C₁₂H₁₆O₄S
• 分子量: 256.323
• InChiKey: CBSVXHQDZYDLKK-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  91.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-4-(tert-butoxy)-4-oxo-2-(thiophen-2-yl)butanoic acid 在 N-溴代丁二酰亚胺(NBS) 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.58h， 生成
  参考文献：
  名称：

  Discovery of the first potent and selective αvβ5 integrin inhibitor based on an amide-containing core

  摘要：

  Integrins α_vβ₅ and α_vβ₃ are closely related, proangiogenic members of the wider RGD-binding integrin family. Due to their high sequence homology, the development of α_vβ₅-selective compounds has remained elusive to synthetic and medicinal chemists. Herein, we describe a survey of SAR around a series of amide-containing 3-aryl-succinamic acid-based RGD mimetics. This resulted in the discovery of α,α,α-trifluorotolyl 12 which exhibits 800 × selectivity for α_vβ₅versus α_vβ₃ with a pyrrolidine amide linker that confers selectivity for α_vβ₅ by positioning a key aryl ring in the SDL of α_vβ₅ with good complementarity; binding in this mode is disfavoured in α_vβ₃ due to clashes with key residues in the β₃-subunit. Compound 12 exhibits selective inhibition by a cell adhesion assay, high passive permeability and solubility which enables potential use of this inhibitor as an α_vβ₅-selective in vitro tool compound.

  DOI：

  10.1016/j.ejmech.2020.112719
• 作为产物：
  描述：

  2-噻吩乙酸 在 双氧水 、 sodium hexamethyldisilazane 、 三甲基乙酰氯 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 生成 (R)-4-(tert-butoxy)-4-oxo-2-(thiophen-2-yl)butanoic acid
  参考文献：
  名称：

  Discovery of the first potent and selective αvβ5 integrin inhibitor based on an amide-containing core

  摘要：

  Integrins α_vβ₅ and α_vβ₃ are closely related, proangiogenic members of the wider RGD-binding integrin family. Due to their high sequence homology, the development of α_vβ₅-selective compounds has remained elusive to synthetic and medicinal chemists. Herein, we describe a survey of SAR around a series of amide-containing 3-aryl-succinamic acid-based RGD mimetics. This resulted in the discovery of α,α,α-trifluorotolyl 12 which exhibits 800 × selectivity for α_vβ₅versus α_vβ₃ with a pyrrolidine amide linker that confers selectivity for α_vβ₅ by positioning a key aryl ring in the SDL of α_vβ₅ with good complementarity; binding in this mode is disfavoured in α_vβ₃ due to clashes with key residues in the β₃-subunit. Compound 12 exhibits selective inhibition by a cell adhesion assay, high passive permeability and solubility which enables potential use of this inhibitor as an α_vβ₅-selective in vitro tool compound.

  DOI：

  10.1016/j.ejmech.2020.112719

文献信息

• [EN] HETEROARYL SUCCINAMIDES AND THEIR USE AS METALLOPROTEINASE INHIBITORS<br/>[FR] SUCCINAMIDES HETEROARYLE ET LEUR UTILISATION COMME INHIBITEURS DE METALLOPROTEINASES
  申请人：AGOURON PHARMACEUTICALS, INC.

  公开号：WO1998017643A1

  公开（公告）日：1998-04-30

  (EN) The present invention is directed to compound of formula (I), wherein R1, R2, R3, R4, R5, X, Y and (Ia) are as defined herein. These compounds are useful for inhibiting the activity of a metalloproteinase by contacting the metalloproteinase with an effective amount of the inventive compounds.(FR) La présente invention porte sur un composé de la formule (I) dans laquelle R1, R2, R3, R4, R5, X, Y et (Ia) sont tels que définis dans la demande. Ces composés sont utiles pour inhiber l'activité d'une métalloprotéinase en mettant en contact cette métalloprotéinase avec une quantité efficace des composés de l'invention.

  该发明涉及化合物(I)的配方，其中R1、R2、R3、R4、R5、X、Y和(Ia)的定义如本文所述。这些化合物可通过与发明化合物的有效量接触金属蛋白酶来抑制其活性。
• Metalloproteinase inhibitors, pharmaceutical compositions containing them, and their use
  申请人：——

  公开号：US20020019429A1

  公开（公告）日：2002-02-14

  The present invention is directed to compound of the formula I: 1 wherein R 1 , R 2 , R 3 , R 4 , R 5 , X, Y, and 2 are as defined herein. These compounds are useful for inhibiting the activity of a metalloproteinase by contacting the metalloproteinase with an effective amount of the inventive compounds.

  本发明涉及公式I的化合物：1其中R1、R2、R3、R4、R5、X、Y和2如此定义。这些化合物通过与一定量的本发明化合物接触来抑制金属蛋白酶的活性。
• HETEROARYL SUCCINAMIDES AND THEIR USE AS METALLOPROTEINASE INHIBITORS
  申请人：AGOURON PHARMACEUTICALS, INC.

  公开号：EP0937042A1

  公开（公告）日：1999-08-25
• US6008243A
  申请人：——

  公开号：US6008243A

  公开（公告）日：1999-12-28
• US6174915B1
  申请人：——

  公开号：US6174915B1

  公开（公告）日：2001-01-16