(S)-5-Benzyl-3-[1-pyridin-4-yl-meth-(E)-ylidene]-pyrrolidin-2-one | 809278-68-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-5-Benzyl-3-[1-pyridin-4-yl-meth-(E)-ylidene]-pyrrolidin-2-one
• CAS: 809278-68-0
• 化学式: C₁₇H₁₆N₂O
• 分子量: 264.327
• InChiKey: GYPZZTHVUMDQLH-INIZCTEOSA-N

物化性质

• 沸点：
  516.5±50.0 °C(Predicted)
• 密度：
  1.198±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  41.99
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (S)-5-Benzyl-3-[1-pyridin-4-yl-meth-(E)-ylidene]-pyrrolidin-2-one 在 Pd(CaCO₃)/C 、 calcium carbonate 盐酸 、 氢气 、 sodium hydride 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 80.0 ℃ 、101.33 kPa 条件下， 生成 (2R,4S)-2-Benzyl-5-((R)-5-benzyl-2-oxo-3-pyridin-4-ylmethyl-pyrrolidin-1-yl)-4-hydroxy-pentanoic acid ((1S,2R)-2-hydroxy-indan-1-yl)-amide
  参考文献：
  名称：

  Discovery of potent pyrrolidone-based HIV-1 protease inhibitors with enhanced drug-like properties

  摘要：

  We have developed efficient syntheses of the HIV-1 protease inhibitor 4 and its analogues, which incorporate the pyrrolidone scaffold 2 as P1-P2 moiety. Evaluation of these analogues in the HIV-1 protease enzyme assay resulted in discovery of potent and more water soluble meta-amino- and meta-hydroxy inhibitors 17b and 19b. The SAR observed in this class of PIs could be rationalized with aid of the X-ray structure of inhibitor 28 co-crystallized with the HIV-1 protease, which suggested that the polar meta- (but not para-) benzyl substituents in P2 could side-step the hydrophobic S2 enzyme active pocket by rotating the P2 moiety around its Cbeta-Cgamma bond. Such reorientation allows to engage the unsubstituted, hydrophobic edge of benzyl moiety in P2 in the requisite P2/S2 hydrophobic interaction, and projects polar meta-substituent into the bound water. It appears that the meta-position can be chemically derivatized without potency loss of thus resulting inhibitors, as evidenced by potent 22-26. We thus identified pyrrolidone 2-based inhibitors exemplified by 17b and 19b, which uniquely accommodate both high enzyme potency and which provide a platform for fine-tuning of drug-like properties in this class of PIs by additional chemical manipulations on the meta-position. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.08.039
• 作为产物：
  描述：

  4-吡啶甲醛 、 (R)-2-氧代-5-苄基-1-吡咯烷羧酸叔丁酯 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 生成 (S)-5-Benzyl-3-[1-pyridin-4-yl-meth-(E)-ylidene]-pyrrolidin-2-one
  参考文献：
  名称：

  Discovery of potent pyrrolidone-based HIV-1 protease inhibitors with enhanced drug-like properties

  摘要：

  We have developed efficient syntheses of the HIV-1 protease inhibitor 4 and its analogues, which incorporate the pyrrolidone scaffold 2 as P1-P2 moiety. Evaluation of these analogues in the HIV-1 protease enzyme assay resulted in discovery of potent and more water soluble meta-amino- and meta-hydroxy inhibitors 17b and 19b. The SAR observed in this class of PIs could be rationalized with aid of the X-ray structure of inhibitor 28 co-crystallized with the HIV-1 protease, which suggested that the polar meta- (but not para-) benzyl substituents in P2 could side-step the hydrophobic S2 enzyme active pocket by rotating the P2 moiety around its Cbeta-Cgamma bond. Such reorientation allows to engage the unsubstituted, hydrophobic edge of benzyl moiety in P2 in the requisite P2/S2 hydrophobic interaction, and projects polar meta-substituent into the bound water. It appears that the meta-position can be chemically derivatized without potency loss of thus resulting inhibitors, as evidenced by potent 22-26. We thus identified pyrrolidone 2-based inhibitors exemplified by 17b and 19b, which uniquely accommodate both high enzyme potency and which provide a platform for fine-tuning of drug-like properties in this class of PIs by additional chemical manipulations on the meta-position. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.08.039