3,4-Difluorocinnamic acid β-phenylethyl ester

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 3,4-Difluorocinnamic acid β-phenylethyl ester
• 英文别名: phenethyl (E)-3-(3,4-difluorophenyl)prop-2-enoate；2-phenylethyl (E)-3-(3,4-difluorophenyl)prop-2-enoate
• 化学式: C₁₇H₁₄F₂O₂
• 分子量: 288.294
• InChiKey: TVFXDGFEJIQXBY-VQHVLOKHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  苯乙醇 、 3,4-二氟肉桂酸 在 对甲苯磺酸 作用下， 以 苯 为溶剂， 以38%的产率得到3,4-Difluorocinnamic acid β-phenylethyl ester
  参考文献：
  名称：

  Hydroxylated Aromatic Inhibitors of HIV-1 Integrase

  摘要：

  Efficient replication of HIV-1 requires integration of a DNA copy of the viral genome into a chromosome of the host cell. Integration is catalyzed by the viral integrase, and we have previously reported that phenolic moieties in compounds such as flavones, caffeic acid phenethyl ester (CAFE, 2), and curcumin confer inhibitory activity against HIV-1 integrase. We now extend these findings by performing a comprehensive structure-activity relationship using CAPE analogues. Approximately 30 compounds have been prepared as HIV integrase inhibitors based on the structural lead provided by CAPE, which has previously been shown to exhibit an IC50 value of 7 mu M in our integration assay. These analogues were designed to examine specific features of the parent CAFE structure which may be important for activity. Among the features examined for their effects on inhibitory potency were ring substitution, side chain length and composition, and phenyl ring conformational orientation. In an assay which measured the combined effect of two sequential steps, dinucleotide cleavage and strand transfer, several analogues have IC50 values for 3'-processing and strand transfer lower than those of CAFE. Inhibition of strand transfer was assayed using both blunt-ended and ''precleaved'' DNA substrates. Disintegration using an integrase mutant lacking the N-terminal zinc finger and C-terminal DNA-binding domains was also inhibited by these analogues, suggesting that the binding site for these compounds resides in the central catalytic core. Several CAFE analogues were also tested for selective activity against transformed cells. Taken together, these results suggest that the development of novel antiviral agents for the treatment of acquired immune deficiency syndrome can be based upon inhibition of HIV-1 integrase.

  DOI：

  10.1021/jm00021a006

文献信息

• Method for the treatment of hyperproliferative epithelial skin diseases
  申请人：The United States of America as represented by the Department of Health

  公开号：US05610185A1

  公开（公告）日：1997-03-11

  The present invention relates to a method of treating hyperproliferative epithelial lesions by topical administration. The method prevents growth and actively cross-links these aberrant cells, thereby killing the cells. The present invention is useful in control and prevention of hyperproliferative epithelial disorders, such as HPV-infected cell lesions, actinic keratosis, melanomas, and malignant and pre-malignant carcinomas.

  本发明涉及一种通过局部给药治疗过度增殖的上皮病变的方法。该方法可以防止细胞的生长并积极地交联这些异常细胞，从而杀死这些细胞。本发明对于控制和预防过度增殖的上皮疾病非常有用，例如HPV感染细胞病变、日光性角化症、黑色素瘤以及恶性和癌前病变的癌症。
• US5610185A
  申请人：——

  公开号：US5610185A

  公开（公告）日：1997-03-11
• Hydroxylated Aromatic Inhibitors of HIV-1 Integrase
  作者：Terrence R. Jr. Burke、Mark Fesen、Abhijit Mazumder、Jessie Yung、Jian Wang、Adelaide M. Carothers、Dezider Grunberger、John Driscoll、Yves Pommier、Kurt Kohn

  DOI：10.1021/jm00021a006

  日期：1995.10

  Efficient replication of HIV-1 requires integration of a DNA copy of the viral genome into a chromosome of the host cell. Integration is catalyzed by the viral integrase, and we have previously reported that phenolic moieties in compounds such as flavones, caffeic acid phenethyl ester (CAFE, 2), and curcumin confer inhibitory activity against HIV-1 integrase. We now extend these findings by performing a comprehensive structure-activity relationship using CAPE analogues. Approximately 30 compounds have been prepared as HIV integrase inhibitors based on the structural lead provided by CAPE, which has previously been shown to exhibit an IC50 value of 7 mu M in our integration assay. These analogues were designed to examine specific features of the parent CAFE structure which may be important for activity. Among the features examined for their effects on inhibitory potency were ring substitution, side chain length and composition, and phenyl ring conformational orientation. In an assay which measured the combined effect of two sequential steps, dinucleotide cleavage and strand transfer, several analogues have IC50 values for 3'-processing and strand transfer lower than those of CAFE. Inhibition of strand transfer was assayed using both blunt-ended and ''precleaved'' DNA substrates. Disintegration using an integrase mutant lacking the N-terminal zinc finger and C-terminal DNA-binding domains was also inhibited by these analogues, suggesting that the binding site for these compounds resides in the central catalytic core. Several CAFE analogues were also tested for selective activity against transformed cells. Taken together, these results suggest that the development of novel antiviral agents for the treatment of acquired immune deficiency syndrome can be based upon inhibition of HIV-1 integrase.