(2R,5S,7S)-1-aza-7-benzyloxycarbonylamino-8-oxo-4-thiabicyclo<3.3.0>octane-2-carboxylic acid methyl ester | 109317-07-9

• 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: (2R,5S,7S)-1-aza-7-benzyloxycarbonylamino-8-oxo-4-thiabicyclo<3.3.0>octane-2-carboxylic acid methyl ester
• 英文别名: methyl (3R,6S,7aS)-5-oxo-6-(phenylmethoxycarbonylamino)-3,6,7,7a-tetrahydro-2H-pyrrolo[2,1-b][1,3]thiazole-3-carboxylate
• CAS: 109317-07-9
• 化学式: C₁₆H₁₈N₂O₅S
• 分子量: 350.395
• InChiKey: SIMGGGUGDLVJKI-AVGNSLFASA-N

物化性质

• 沸点：
  572.9±50.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2R,5S,7S)-1-aza-7-benzyloxycarbonylamino-8-oxo-4-thiabicyclo<3.3.0>octane-2-carboxylic acid methyl ester 在 氨 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以100%的产率得到(2R,5S,7S)-1-aza-7-benzyloxycarbonylamino-8-oxo-4-thiabicyclo[3.3.0]octane-2-carboxamide
  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：

  (S)-(+)-3(苄氧羰基)-5-氧代-4-恶唑啉乙酸 在 吡啶 、 氯化亚砜 、 三正丁基氢锡 、 sodium carbonate 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 85.33h， 生成 (2R,5S,7S)-1-aza-7-benzyloxycarbonylamino-8-oxo-4-thiabicyclo<3.3.0>octane-2-carboxylic acid methyl ester
  参考文献：
  名称：

  恶唑烷酮合成双环γ-内酰胺

  摘要：

  恶唑烷酮醛10在双环化反应中与L-半胱氨酸甲酯反应生成N-羟甲基双环γ-内酰胺11。用D-半胱氨酸甲酯，得到N-羟甲基双环γ-内酰胺12的差向异构体混合物。双环γ-内酰胺3、4和13可由11和12轻松制得。

  DOI：

  10.1016/s0040-4020(01)88118-7

文献信息

• A γ-lactam analogue of the penems possessing antibacterial activity
  作者：Jack E. Baldwin、Richard T. Freeman、Christopher Lowe、Christopher J. Schofield、Eun Lee

  DOI：10.1016/s0040-4020(01)89088-8

  日期：——

  The synthesis of a γ-lactam analogue of penems, from aspartic acid semi-aldehyde, which possessed antibacterial activity is described.1,2

  描述了由具有抗菌活性的天冬氨酸半醛合成青霉素的γ-内酰胺类似物。1,2
• A γ-lactam analogue of penems possessing antibacterial activity
  作者：Jack E Baldwin、Christopher Lowe、Christopher J Schofield、Eun Lee

  DOI：10.1016/s0040-4039(00)84822-4

  日期：1986.1

  The synthesis of a γ-lactam analogue of the penems, which showed antibacterial activity, is described.

  描述了具有抗菌活性的青霉素的γ-内酰胺类似物的合成。
• BALDWIN, JACK E.;FREEMAN, RICHARD T.;LOWE, CHRISTOPHER;SCHOFIELD, CHRISTO+, TETRAHEDRON, 45,(1989) N4, C. 4537-4550
  作者：BALDWIN, JACK E.、FREEMAN, RICHARD T.、LOWE, CHRISTOPHER、SCHOFIELD, CHRISTO+

  DOI：——

  日期：——
• Synthesis of bicyclic γ-lactams via oxazolidinones
  作者：Jack E. Baldwin、E. Lee

  DOI：10.1016/s0040-4020(01)88118-7

  日期：1986.1

  Oxazolidinone aldehyde 10 reacts with L-cysteine methyl ester to produce N-hydroxymethyl bicyclic γ-lactam 11 in a double cyclisation reaction. With D-cysteine methyl ester, an epimeric mixture of N-hydroxymethyl bicyclic γ-lactams 12 is obtained. Bicyclic γ-lactams 3, 4 and 13 are easily prepared from 11 and 12.

  恶唑烷酮醛10在双环化反应中与L-半胱氨酸甲酯反应生成N-羟甲基双环γ-内酰胺11。用D-半胱氨酸甲酯，得到N-羟甲基双环γ-内酰胺12的差向异构体混合物。双环γ-内酰胺3、4和13可由11和12轻松制得。
• Constrained Peptidomimetics Reveal Detailed Geometric Requirements of Covalent Prolyl Oligopeptidase Inhibitors
  作者：Janice Lawandi、Sylvestre Toumieux、Valentine Seyer、Philip Campbell、Sabine Thielges、Lucienne Juillerat-Jeanneret、Nicolas Moitessier

  DOI：10.1021/jm901013a

  日期：2009.11.12

  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.