mono-t-butyl 3(R)-phenethylsuccinate | 156109-58-9

• 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: mono-t-butyl 3(R)-phenethylsuccinate
• 英文别名: (R)-4-(tert-Butoxy)-4-oxo-2-phenethylbutanoic acid；(2R)-4-[(2-methylpropan-2-yl)oxy]-4-oxo-2-(2-phenylethyl)butanoic acid
• CAS: 156109-58-9
• 化学式: C₁₆H₂₂O₄
• 分子量: 278.348
• InChiKey: BKBDCHIWGLDPNK-CYBMUJFWSA-N

物化性质

• 沸点：
  410.6±38.0 °C(Predicted)
• 密度：
  1.100±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  mono-t-butyl 3(R)-phenethylsuccinate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 (3R)-3-[[(1S)-2-(methylamino)-2-oxo-1-phenylethyl]carbamoyl]-5-phenylpentanoic acid
  参考文献：
  名称：

  Inhibition of Membrane-Type 1 Matrix Metalloproteinase by Hydroxamate Inhibitors:  An Examination of the Subsite Pocket

  摘要：

  The membrane-type 1 matrix metalloproteinase (MT1-MMP) has been reported to mediate the activation of pro-gelatinase A (proMMP-2), which is associated with tumor proliferation and metastasis. MT1-MMP can also digest extracellular matrix (ECM) such as interstitial collagens, gelatin, and proteoglycan and thus may play an important role in pathophysiological digestion of ECM. We studied the inhibitory effect of various hydroxamate MMP inhibitors, including known inhibitors such as BB-94, BB-2516, GM6001, and Ro31-9790, on a deletion mutant of MT1-MMP lacking the transmembrane domain (Delta MT1) to further characterize the enzyme and develop a selective inhibitor for MT1-MMP. The evaluation of the inhibitory activities of various hydroxamates reveals general structural profiles affecting selectivities toward MMPs. In particular, a longer side chain at the P1' position is preferable for the binding to MMP-2, -3, and -9 and MT1-MMP. For the P2' position, an a-branched alkyl group is critical for the binding toward Delta MT1, while the introduction of a bulky group at the a-position of hydroxamic acid seems to diminish the activity against Delta MT1. Summation of the data on the sensitivity of Delta MT1 to various hydroxamate inhibitors indicates that (1) the volume of the S1' subsite of Delta MT1 is similar to that of MMP-2, -3, and -9, which is bigger than that of MMP-1, and (2) the S1 and S2' subsites are narrower than those in other MMPs. On the basis of these results, the hydroxamates with a P1' phenylpropyl and P2' alpha-branched alkyl group were synthesized and evaluated for inhibitory activity. These inhibitors (1h,i) showed strong activity against Delta MT1 over MMP-1, but no selectivity between Delta MT1 and MMP-9. These results are explained using molecular modeling studies conducted on MT1-MMP.

  DOI：

  10.1021/jm970404a
• 作为产物：
  描述：

  (S)-4-benzyl-3-(3-phenylbutanoyl)oxazolidin-2-one 在 lithium hydroxide 、 双氧水 、 lithium diisopropyl amide 、 sodium nitrite 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 2.0h， 生成 mono-t-butyl 3(R)-phenethylsuccinate
  参考文献：
  名称：

  Inhibition of Membrane-Type 1 Matrix Metalloproteinase by Hydroxamate Inhibitors:  An Examination of the Subsite Pocket

  摘要：

  The membrane-type 1 matrix metalloproteinase (MT1-MMP) has been reported to mediate the activation of pro-gelatinase A (proMMP-2), which is associated with tumor proliferation and metastasis. MT1-MMP can also digest extracellular matrix (ECM) such as interstitial collagens, gelatin, and proteoglycan and thus may play an important role in pathophysiological digestion of ECM. We studied the inhibitory effect of various hydroxamate MMP inhibitors, including known inhibitors such as BB-94, BB-2516, GM6001, and Ro31-9790, on a deletion mutant of MT1-MMP lacking the transmembrane domain (Delta MT1) to further characterize the enzyme and develop a selective inhibitor for MT1-MMP. The evaluation of the inhibitory activities of various hydroxamates reveals general structural profiles affecting selectivities toward MMPs. In particular, a longer side chain at the P1' position is preferable for the binding to MMP-2, -3, and -9 and MT1-MMP. For the P2' position, an a-branched alkyl group is critical for the binding toward Delta MT1, while the introduction of a bulky group at the a-position of hydroxamic acid seems to diminish the activity against Delta MT1. Summation of the data on the sensitivity of Delta MT1 to various hydroxamate inhibitors indicates that (1) the volume of the S1' subsite of Delta MT1 is similar to that of MMP-2, -3, and -9, which is bigger than that of MMP-1, and (2) the S1 and S2' subsites are narrower than those in other MMPs. On the basis of these results, the hydroxamates with a P1' phenylpropyl and P2' alpha-branched alkyl group were synthesized and evaluated for inhibitory activity. These inhibitors (1h,i) showed strong activity against Delta MT1 over MMP-1, but no selectivity between Delta MT1 and MMP-9. These results are explained using molecular modeling studies conducted on MT1-MMP.

  DOI：

  10.1021/jm970404a

文献信息

• [EN] BETA-TETRAZOLYL-PROPIONIC ACIDS AS METALLO-BETA-LACTAMASE INHIBITORS<br/>[FR] ACIDES BÊTA-TÉTRAZOLYLE-PROPIONIQUES UTILES EN TANT QU'INHIBITEURS DES MÉTALLO-BÊTA-LACTAMASES
  申请人：MERCK SHARP & DOHME

  公开号：WO2015171474A1

  公开（公告）日：2015-11-12

  The present invention relates to compounds of formula I that are metallo-β-lactamase inhibitors, the synthesis of such compounds, and the use of such compounds for use with β-lactam antibiotics for overcoming resistance.

  本发明涉及公式I的化合物，这些化合物是金属β-内酰胺酶抑制剂，以及这些化合物的合成和与β-内酰胺类抗生素一起使用以克服抗性的用途。
• Method of preparing optically active homo-beta-amino acids
  申请人：MONSANTO COMPANY

  公开号：EP0561758A3

  公开（公告）日：1995-04-05

  The present invention is directed to synthesis of homo-β-amino acids of an optical purity sufficient to exhibit optical activity wherein Curtius rearrangement of 3-mono-substituted succinate acid half ester of an optical purity sufficient to exhibit optical activity is affected and the incipient isocyanate is trapped with a primary or secondary alcohol. The resulting carbamate-protected homo-β-amino esters are then saponified to produce the corresponding carbamate-protected homo-β-amino acids which are deprotected to yield homo-β-amino acids of an optical purity sufficient to exhibit optical activity.

  本发明旨在合成具有足够光学活性以表现光学活性的同型β-氨基酸，其中影响了具有足够光学活性的3-单取代琥珀酸半酯的Curtius重排，并且初级异氰酸酯被一级或二级醇捕获。然后，产生的羰基保护的同型β-氨基酸酯被皂化以产生相应的羰基保护的同型β-氨基酸，然后去保护以产生具有足够光学活性以表现光学活性的同型β-氨基酸。
• COMPOUNDS, PHARMACEUTICAL COMPOSITION AND METHODS FOR USE IN TREATING METABOLIC DISORDERS
  申请人：Hoveyda Hamid

  公开号：US20110230477A1

  公开（公告）日：2011-09-22

  The present invention is directed to novel compounds of formula (I) and their use in treating metabolic diseases.

  本发明涉及式（I）的新化合物及其在治疗代谢性疾病方面的应用。
• MATRIX METALLOPROTEINASE INHIBITORS
  申请人：LEO PHARMA A/S (with secondary name: LEO PHARMACEUTICAL PRODUCTS LTD. A/S)

  公开号：EP1060161B1

  公开（公告）日：2003-06-11
• Compounds, pharmaceutical composition and methods for use in treating metabolic disorders
  申请人：Euroscreen S.A.

  公开号：EP2364297A1

  公开（公告）日：2011-09-14