3-Dodecanoyl-4-hydroxy-6-undecyl-pyran-2-one | 107617-18-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-Dodecanoyl-4-hydroxy-6-undecyl-pyran-2-one
• 英文别名: 3-Dodecanoyl-4-hydroxy-6-undecylpyran-2-one
• CAS: 107617-18-5
• 化学式: C₂₈H₄₈O₄
• 分子量: 448.687
• InChiKey: JIGTZBQPVRSJJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.2
• 重原子数：
  32
• 可旋转键数：
  21
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.79
• 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：

  3-Dodecanoyl-4-hydroxy-6-undecyl-pyran-2-one 在 硫酸 作用下， 反应 0.25h， 生成 4-羟基-6-十一烷基-2H-吡喃-2-酮
  参考文献：
  名称：

  Inhibition of human sputum elastase by substituted 2-pyrones. 2

  摘要：

  Nineteen 4-hydroxy- and 4-methoxy-2-pyrones related to elasnin (I) have been assayed for in vitro inhibition of human sputum elastase (HSE), porcine pancreatic elastase, alpha-chymotrypsin, and trypsin. Inhibition is reported as Ki and Ki'; percentage inhibition was dependent on [S] in a number of cases, making it unsuitable as a measure of relative inhibition. The 3-(1-oxoalkyl)-4-hydroxy-6-alkyl-2-pyrones were found to be most effective, the octyl homologue 11 being the most potent inhibitor (Ki = 4.6 microM, 30 times better than the lead compound). A further reduction in inhibition was observed when the hitherto hydrophobic 6-substituent was substituted by a branched functionality of hydrophilic nature. Conversely, methylation of the 4-hydroxy group of the 6-alkyl-2-pyrones increased inhibitory activity. The mechanism of inhibition varied from pure noncompetitive to mixed type to uncompetitive and was found to be dependent on the pattern of substitution. We believe that the 4-hydroxy-2-pyrone binds to the S4 subsite, with the 6-substituent extending across the S4-S1 subsites and the 3-substituent occupying the S5 subsite. The length of the inhibitor binding region was calculated to be approximately 24 A. None of the hydrophobic compounds were found to have any appreciable inhibition (less than 10%) with porcine pancreatic elastase, bovine alpha-chymotrypsin, and bovine trypsin when tested at the limit of their solubility. The hydrophilic compounds were nonspecific, inhibiting all four enzymes. Dialysis was used to show that the interaction is fully reversible.

  DOI：

  10.1021/jm00389a010
• 作为产物：
  描述：

  3-氧代十四烷酸 在 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 生成 3-Dodecanoyl-4-hydroxy-6-undecyl-pyran-2-one
  参考文献：
  名称：

  Inhibition of human sputum elastase by substituted 2-pyrones. 2

  摘要：

  Nineteen 4-hydroxy- and 4-methoxy-2-pyrones related to elasnin (I) have been assayed for in vitro inhibition of human sputum elastase (HSE), porcine pancreatic elastase, alpha-chymotrypsin, and trypsin. Inhibition is reported as Ki and Ki'; percentage inhibition was dependent on [S] in a number of cases, making it unsuitable as a measure of relative inhibition. The 3-(1-oxoalkyl)-4-hydroxy-6-alkyl-2-pyrones were found to be most effective, the octyl homologue 11 being the most potent inhibitor (Ki = 4.6 microM, 30 times better than the lead compound). A further reduction in inhibition was observed when the hitherto hydrophobic 6-substituent was substituted by a branched functionality of hydrophilic nature. Conversely, methylation of the 4-hydroxy group of the 6-alkyl-2-pyrones increased inhibitory activity. The mechanism of inhibition varied from pure noncompetitive to mixed type to uncompetitive and was found to be dependent on the pattern of substitution. We believe that the 4-hydroxy-2-pyrone binds to the S4 subsite, with the 6-substituent extending across the S4-S1 subsites and the 3-substituent occupying the S5 subsite. The length of the inhibitor binding region was calculated to be approximately 24 A. None of the hydrophobic compounds were found to have any appreciable inhibition (less than 10%) with porcine pancreatic elastase, bovine alpha-chymotrypsin, and bovine trypsin when tested at the limit of their solubility. The hydrophilic compounds were nonspecific, inhibiting all four enzymes. Dialysis was used to show that the interaction is fully reversible.

  DOI：

  10.1021/jm00389a010

文献信息

• EP0365539A4
  申请人：——

  公开号：EP0365539A4

  公开（公告）日：1990-12-05
• HUMAN LEUCOCYTE ELASTASE INHIBITOR COMPOUNDS
  申请人：AUSTRALIAN COMMERCIAL RESEARCH & DEVELOPMENT LIMITED

  公开号：EP0365539A1

  公开（公告）日：1990-05-02
• [EN] HUMAN LEUCOCYTE ELASTASE INHIBITOR COMPOUNDS
  申请人：LA TROBE UNIVERSITY

  公开号：WO1988010258A1

  公开（公告）日：1988-12-29

  (EN) A compound of formula (III) or physiologically acceptable salts thereof, wherein: Z is a bond, -O- or -NH-; R1 and R3 are independently selected from C5-12 substituted of unsubstituted hydrocarbon radicals; R2 is hydrogen or a C1-5 substituted or unsubstituted hydrocarbon radical; said substituted hydrocarbon radicals are substituted with physiologically innocuous substituents which do not interfere with the binding of said compound with elastase-type enzymes; provided that: when R1 is oxohexyl and R2 is hydrogen, then R3 cannot be pentyl; when R1 is oxoheptyl and R2 is hydrogen, then R3 cannot be hexyl; when R1 is oxononyl and R2 is hydrogen, then R3 cannot be octyl; when R1 is oxodecyl and R2 is hydrogen, then R3 cannot be nonyl; and when R1 is oxododecyl and R2 is hydrogen, then R3 cannot be undecyl. These compounds are potent and specific inhibitor compounds fo elastase-type enzymes, especially for human leucocytic elastase (HLE) and can be expected to be useful in the treatment of elastase-type implicated diseases such as arthritis, tumor growth and emphysema. Production, method of use and pharmaceutical compositions containing these compounds are disclosed.(FR) La présente invention se rapporte à un composé représenté par la formule (III) ou à des sels physiologiquement acceptables dudit composé, où: Z représente une liaison, -O- ou -NH-; R1 et R3 sont choisis séparément parmi des radicaux d'hydrocarbures substitués ou non substitués de 5 à 12 atomes de carbone; R2 représente un hydrogène ou un radical d'hydrocarbures substitués ou non substitués de 1 à 5 atomes de carbone; lesdits radicaux d'hydrocarbures substitués étant substitués par des substituants physiologiquement inoffensifs qui ne perturbent pas la liaison entre ledit composé et les enzymes du type élastase; à condition que: lorsque R1 représente un oxohexyle et R2 un hydrogène, alors R3 ne peut pas être un pentyle; lorsque R1 représente un oxoheptyle et R2 un hydrogène, alors R3 ne peut pas être un hexyle; lorsque R1 représente un oxononyle et R2 un hydrogène, alors R3 ne peut pas être un octyle; lorsque R1 un oxodécyle et R2 un hydrogène, alors R3 ne peut pas être un nonyle; et lorsque R1 représente un oxodécyle et R2 un hydrogène, alors R3 nepeut pas être un undécyle. Ces composés constituent des composés inhibiteurs puissants et spécifiques pour les enzymes du type élastase, tel que notamment l'élastase leucocytaire humaine, (HLE) et on peut prévoir que ces composés ont une utilité dans le traitement des maladies dans lesquelles sont impliquées des enzymes du type élastase, tel que l'arthrite, la croissance des tumeurs et les emphysèmes. La production et le procédé d'utilisation de ces composés ainsi que des compositions pharmaceutiques les contenant sont également décrits.
• Inhibition of human sputum elastase by substituted 2-pyrones. 2
  作者：Luisa Cook、Bela Ternai、Peter Ghosh

  DOI：10.1021/jm00389a010

  日期：1987.6

  Nineteen 4-hydroxy- and 4-methoxy-2-pyrones related to elasnin (I) have been assayed for in vitro inhibition of human sputum elastase (HSE), porcine pancreatic elastase, alpha-chymotrypsin, and trypsin. Inhibition is reported as Ki and Ki'; percentage inhibition was dependent on [S] in a number of cases, making it unsuitable as a measure of relative inhibition. The 3-(1-oxoalkyl)-4-hydroxy-6-alkyl-2-pyrones were found to be most effective, the octyl homologue 11 being the most potent inhibitor (Ki = 4.6 microM, 30 times better than the lead compound). A further reduction in inhibition was observed when the hitherto hydrophobic 6-substituent was substituted by a branched functionality of hydrophilic nature. Conversely, methylation of the 4-hydroxy group of the 6-alkyl-2-pyrones increased inhibitory activity. The mechanism of inhibition varied from pure noncompetitive to mixed type to uncompetitive and was found to be dependent on the pattern of substitution. We believe that the 4-hydroxy-2-pyrone binds to the S4 subsite, with the 6-substituent extending across the S4-S1 subsites and the 3-substituent occupying the S5 subsite. The length of the inhibitor binding region was calculated to be approximately 24 A. None of the hydrophobic compounds were found to have any appreciable inhibition (less than 10%) with porcine pancreatic elastase, bovine alpha-chymotrypsin, and bovine trypsin when tested at the limit of their solubility. The hydrophilic compounds were nonspecific, inhibiting all four enzymes. Dialysis was used to show that the interaction is fully reversible.