N-[3-[cyclopropyl-(4-hydroxy-2-oxo-5,6,7,8,9,10-hexahydrocycloocta[b]pyran-3-yl)methyl]phenyl]-2-phenyl-acetamide | 166334-72-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃
• 英文名称: N-[3-[cyclopropyl-(4-hydroxy-2-oxo-5,6,7,8,9,10-hexahydrocycloocta[b]pyran-3-yl)methyl]phenyl]-2-phenyl-acetamide
• 英文别名: N-[3-[cyclopropyl-(4-hydroxy-2-oxo-5,6,7,8,9,10-hexahydrocycloocta[b]pyran-3-yl)methyl]phenyl]-2-phenylacetamide
• CAS: 166334-72-1
• 化学式: C₂₉H₃₁NO₄
• 分子量: 457.569
• InChiKey: INPIRATUHYARAF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-[3-[cyclopropyl-(4-hydroxy-2-oxo-5,6,7,8,9,10-hexahydrocycloocta[b]pyran-3-yl)methyl]phenyl]-2-phenyl-acetamide 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 1.5h， 以54%的产率得到N-<3-pyran-3-yl)methyl>phenyl>benzeneethanethioamide
  参考文献：
  名称：

  Structure-Based Design of Nonpeptidic HIV Protease Inhibitors from a Cyclooctylpyranone Lead Structure

  摘要：

  Recently, the novel cyclooctylpyranone HIV protease inhibitor 1 was identified in our labs, and an X-ray structure of this inhibitor complexed with HIV-2 protease was obtained. This crystal structure was used to develop two strategies for creating derivatives of 1 with enhanced enzyme inhibitory activity. The first strategy, substitution on the cyclooctyl ring, met with limited success, but provided some interesting information about the conformationally-flexible cyclooctyl ring on the inhibitors. The second strategy, substitution at the meta position of the aryl ring, was far more successful and generated compounds, such as the carboxamide derivatives 41 (K-i = 3.0 +/- 0.4 nM) and 36 (K-i = 4.0 +/- 0.8 nM), which were significantly more active than the corresponding unsubstituted cyclooctylpyranone 2 (K-i = 11.7 +/- 4.7 nM). An X-ray crystal structure of 36 complexed with HIV-1 protease indicated the increase in binding affinity is most likely due to the additional interactions between the amide substituent and the S3 region of the protease.

  DOI：

  10.1021/jm00022a011
• 作为产物：
  描述：

  m-<(benzyloxycarbonyl)amino>phenyl cyclopropyl carbinol 在 palladium on activated charcoal 双(2-氧代-3-恶唑烷基)次磷酰氯 、 对甲苯磺酸 、 三乙胺 、 环己烯 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 44.0h， 生成 N-[3-[cyclopropyl-(4-hydroxy-2-oxo-5,6,7,8,9,10-hexahydrocycloocta[b]pyran-3-yl)methyl]phenyl]-2-phenyl-acetamide
  参考文献：
  名称：

  Structure-Based Design of Nonpeptidic HIV Protease Inhibitors from a Cyclooctylpyranone Lead Structure

  摘要：

  Recently, the novel cyclooctylpyranone HIV protease inhibitor 1 was identified in our labs, and an X-ray structure of this inhibitor complexed with HIV-2 protease was obtained. This crystal structure was used to develop two strategies for creating derivatives of 1 with enhanced enzyme inhibitory activity. The first strategy, substitution on the cyclooctyl ring, met with limited success, but provided some interesting information about the conformationally-flexible cyclooctyl ring on the inhibitors. The second strategy, substitution at the meta position of the aryl ring, was far more successful and generated compounds, such as the carboxamide derivatives 41 (K-i = 3.0 +/- 0.4 nM) and 36 (K-i = 4.0 +/- 0.8 nM), which were significantly more active than the corresponding unsubstituted cyclooctylpyranone 2 (K-i = 11.7 +/- 4.7 nM). An X-ray crystal structure of 36 complexed with HIV-1 protease indicated the increase in binding affinity is most likely due to the additional interactions between the amide substituent and the S3 region of the protease.

  DOI：

  10.1021/jm00022a011

文献信息

• 4-HYDROXY-BENZOPYRAN-2-ONES AND 4-HYDROXY-CYCLOALKYL B]PYRAN-2-ONES USEFUL TO TREAT RETROVIRAL INFECTIONS
  申请人：PHARMACIA & UPJOHN COMPANY

  公开号：EP0682663B1

  公开（公告）日：2001-04-18
• [EN] 4-HYDROXY-BENZOPYRAN-2-ONES AND 4-HYDROXY-CYCLOALKYL[B]PYRAN-2-ONES USEFUL TO TREAT RETROVIRAL INFECTIONS<br/>[FR] 4-HYDROXY-BENZOPYRANE-2-ONES ET 4-HYDROXY-CYCLOALKYLE-[B]PYRANE-2-ONES UTILES POUR LE TRAITEMENT DES INFECTIONS RETROVIRALES
  申请人：THE UPJOHN COMPANY

  公开号：WO1994018188A1

  公开（公告）日：1994-08-18

  (EN) The present invention relates to compounds of formula (I) which are 4-hydroxy-benzopyran-2-ones and 4-hydroxy-cycloalkyl[b]pyran-2-ones useful for inhibiting a retrovirus in a mammalian cell infected with said retrovirus. In formula (I) R10 and R20 taken together are formula (II) or formula (III).(FR) Composés de la formule (I) correspondant à des 4-hydroxy-benzopyrane-2-ones et à des 4-hydroxy-cycloalkyle[b]pyrane-2-ones employés pour l'inhibition d'un rétrovirus dans une cellule de mammifère infectée par ledit rétrovirus. Dans la formule (I) R10 et R20 considérés ensemble sont (II) ou (III).
• Structure-Based Design of Nonpeptidic HIV Protease Inhibitors from a Cyclooctylpyranone Lead Structure
  作者：Karen R. Romines、Keith D. Watenpaugh、W. Jeffrey Howe、Paul K. Tomich、Kristine D. Lovasz、Jeanette K. Morris、Musiri N. Janakiraman、Janet C. Lynn、Miao-Miao Horng

  DOI：10.1021/jm00022a011

  日期：1995.10

  Recently, the novel cyclooctylpyranone HIV protease inhibitor 1 was identified in our labs, and an X-ray structure of this inhibitor complexed with HIV-2 protease was obtained. This crystal structure was used to develop two strategies for creating derivatives of 1 with enhanced enzyme inhibitory activity. The first strategy, substitution on the cyclooctyl ring, met with limited success, but provided some interesting information about the conformationally-flexible cyclooctyl ring on the inhibitors. The second strategy, substitution at the meta position of the aryl ring, was far more successful and generated compounds, such as the carboxamide derivatives 41 (K-i = 3.0 +/- 0.4 nM) and 36 (K-i = 4.0 +/- 0.8 nM), which were significantly more active than the corresponding unsubstituted cyclooctylpyranone 2 (K-i = 11.7 +/- 4.7 nM). An X-ray crystal structure of 36 complexed with HIV-1 protease indicated the increase in binding affinity is most likely due to the additional interactions between the amide substituent and the S3 region of the protease.