methyl 2-[(benzyloxycarbonyl)amino]-4-oxobutanoate | 96921-58-3

• 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: methyl 2-[(benzyloxycarbonyl)amino]-4-oxobutanoate
• 英文别名: methyl 4-oxo-2-(phenylmethoxycarbonylamino)butanoate
• CAS: 96921-58-3
• 化学式: C₁₃H₁₅NO₅
• 分子量: 265.266
• InChiKey: JDNZWLRSLDLSCR-UHFFFAOYSA-N

物化性质

• 沸点：
  441.5±45.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  19
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 2-[(benzyloxycarbonyl)amino]-4-oxobutanoate 、 L-苏氨酸甲酯盐酸盐 在 吡啶 作用下， 反应 87.0h， 以35%的产率得到(2S,3R,5S)-1-aza-7-benzyloxycarbonylamino-8-oxo-4-oxa-3-methylbicyclo[3.3.0]octane-2-carboxylic acid methyl ester
  参考文献：
  名称：

  Constrained Peptidomimetics Reveal Detailed Geometric Requirements of Covalent Prolyl Oligopeptidase Inhibitors

  摘要：

  Prolyl oligopeptidases cleave peptides on the carboxy side of internal proline residues and their inhibition has potential in the treatment of human brain disorders. Using our docking program FITTED, we have designed a series of constrained covalent inhibitors, built from a series of bicyclic scaffolds, to study the optimal shape required for these small molecules. These structures bear nitrile functional groups that we predicted to covalently bind to the catalytic serine of the enzyme. Synthesis and biological assays using human brain-derived astrocytic cells and endothelial cells and human fibroblasts revealed that these compounds act as selective inhibitors of prolyl oligopeptidase activity compared to prolyl-dipeptidyl-aminopeptidase activity, are able to penetrate the cells and inhibit intracellular activities in intact living cells. This integrated computational and experimental study shed light oil the binding mode of inhibitors in the enzyme active site and will guide the design of future drug-like molecules.

  DOI：

  10.1021/jm901013a
• 作为产物：
  描述：

  methyl N^α-benzyloxycarbonylamino-γ-nitrobutyrate 在 吡啶 、 二甲基硫 、 氧气 、 苄基三甲基氢氧化铵 、 臭氧 作用下， 生成 methyl 2-[(benzyloxycarbonyl)amino]-4-oxobutanoate
  参考文献：
  名称：

  New synthetic routes to α-amino acids and γ-oxygenated α-amino acids. Reductive denitration and oxidative transformations of γ-nitro-α-amino acids

  摘要：

  通过还原去硝化，γ-硝基-α-氨基酸衍生物可以转化为α-氨基酸；通过对应氨基酸酯硝酸盐衍生物的臭氧解聚，可以转化为γ-氧-α-氨基酸；而通过随后的氧功能团还原，可以转化为γ-羟基-α-氨基酸衍生物，这些转化反应均能获得较高的产率。由于γ-硝基-α-氨基酸衍生物是从N,O保护的脱氢丙氨酸制备而成，而后者又是通过特定途径从相应的丙氨酸、丝氨酸和半胱氨酸衍生物得到的，因此整体程序提供了一种选择性将这些简单的α-氨基酸转化为更复杂的氨基酸的方法。

  DOI：

  10.1039/a707067e

文献信息

• γ-Phosphono-γ-lactones. The use of allyl esters as easily removable phosphonate protecting groups
  作者：Matthias Kamber、George Just

  DOI：10.1139/v85-136

  日期：1985.4.1

  During the synthesis of γ-lactones bearing a phosphonic acid group at the γ-position, difficulties were encountered generating the free phosphonic acids from corresponding esters. A protecting group used for carboxylic acids was adapted to phosphonic acids, making this transformation easy.

  在γ-位带有膦酸基团的γ-内酯的合成过程中，遇到了从相应的酯生成游离膦酸的困难。用于羧酸的保护基团适用于膦酸，使这种转化变得容易。
• AMINO ACID COMPOUNDS AND METHODS OF USE
  申请人：Pliant Therapeutics, Inc.

  公开号：US20190276449A1

  公开（公告）日：2019-09-12

  The invention relates to compounds of formula (A) and formula (I): or a salt thereof, wherein R 1 , R 2 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , q and p are as described herein. Compounds of formula (A), formula (I), and pharmaceutical compositions thereof are αvβ6 integrin inhibitors that are useful for treating fibrosis such as idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP).

  该发明涉及以下化合物的公式(A)和公式(I)：或其盐，其中R1、R2、R10、R11、R12、R13、R14、R15、R16、q和p如本文所述。公式(A)、公式(I)的化合物及其药物组合物是αvβ6整合素抑制剂，可用于治疗纤维化疾病，如特发性肺纤维化（IPF）和非特异性间质性肺炎（NSIP）。
• [EN] DOSAGE FORMS AND REGIMENS FOR AMINO ACID COMPOUNDS<br/>[FR] FORMES POSOLOGIQUES ET SCHÉMAS DE TRAITEMENT POUR DES COMPOSÉS D'ACIDES AMINÉS
  申请人：PLIANT THERAPEUTICS INC

  公开号：WO2020210404A1

  公开（公告）日：2020-10-15

  The invention relates to dosage forms for daily administration of compounds of formula (A) and formula (I): or a salt thereof, wherein R1, R2, R10, R11, R12, R13, R14, R15, R16, q and p are as described herein. Compounds of formula (A), formula (I), and pharmaceutical compositions thereof are ανβ6 integrin inhibitors that are useful for treating fibrosis such as idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP),

  该发明涉及用于每日给药的化合物(A)和化合物(I)的剂型：或其盐，其中R1、R2、R10、R11、R12、R13、R14、R15、R16、q和p如本文所述。化合物(A)、化合物(I)及其药物组成物是ανβ6整合素抑制剂，可用于治疗纤维化疾病，如特发性肺纤维化（IPF）和非特异性间质性肺炎（NSIP）。
• [EN] TREATMENT OF RESPIRATORY DISEASES WITH AMINO ACID COMPOUNDS<br/>[FR] TRAITEMENT DE MALADIES RESPIRATOIRES AVEC DES COMPOSÉS ACIDES AMINÉS
  申请人：PLIANT THERAPEUTICS INC

  公开号：WO2021225912A1

  公开（公告）日：2021-11-11

  The invention relates to methods of therapy using compounds of formula (I) and formula (II): or a salt thereof, wherein R1, R2, R10, R11, R12, R13, R14, R15, R16, q and p are as described herein. Compounds of formula (II) and pharmaceutical compositions thereof are integrin inhibitors that are useful in therapy for a condition, for example, caused by or associated with an infectious agent, shock, pancreatitis, or trauma. The condition can include one or more of pulmonary fibrosis associated with rheumatoid arthritis or progressive familial intrahepatic cholestasis (PFIC).

  该发明涉及使用化合物的疗法方法的公式(I)和公式(II)：或其盐，其中R1、R2、R10、R11、R12、R13、R14、R15、R16、q和p如此处所述。公式(II)的化合物及其药物组成物是整合素抑制剂，可用于治疗某种疾病，例如由感染性因子、休克、胰腺炎或创伤引起或相关的疾病。该疾病可能包括与类风湿性关节炎或进行性家族性肝内胆汁淤积症（PFIC）相关的肺纤维化。
• [EN] PROTECTED DERIVATIVES OF 2-AMINO-4-PHOSPHOBUTANOIC ACID<br/>[FR] DÉRIVÉS PROTÉGÉS D'ACIDE 2-AMINO-4-PHOSPHOBUTANOÏQUE
  申请人：AGENUS INC

  公开号：WO2017165416A1

  公开（公告）日：2017-09-28

  Provided herein are phosphonate compounds useful for the manufacture of serine phosphopeptide mimetics.

  本文提供了磷酸酯化合物，用于制造丝氨酸磷酸肽类似物。