6,7-二羟基-2-萘甲酰胺 | 146515-37-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 6,7-二羟基-2-萘甲酰胺
• 英文名称: 6,7-dihydroxy-2-naphthalenecarboxamide
• 英文别名: 6,7-Dihydroxynaphthalene-2-carboxamide
• CAS: 146515-37-9
• 化学式: C₁₁H₉NO₃
• 分子量: 203.197
• InChiKey: PXGLKMVBMFGFCW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  83.6
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6,7-二羟基-2-萘甲酰胺 在 盐酸 、 对甲苯磺酸 作用下， 以 苯 为溶剂， 反应 72.0h， 生成 6,7-Dihydroxy-2-naphthoic 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
• 作为产物：
  描述：

  6,7-二甲氧基萘-2-羧酸 在 氯化亚砜 、 氨 、 三溴化硼 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 6.5h， 生成 6,7-二羟基-2-萘甲酰胺
  参考文献：
  名称：

  Bicyclic compounds as ring-constrained inhibitors of protein-tyrosine kinase p56lck

  摘要：

  A study was undertaken to prepare inhibitors of the lymphocyte protein-tyrosine kinase p56lck. Using the known p56lck inhibitor 3,4-dihydroxy-alpha-cyanocinnamamide (4) as a lead compound, bicyclic analogues were designed as conformationally constrained mimetics in which the phenyl ring and vinyl side chain of the cinnamamide are locked into a coplanar orientation. Such planarity was rationalized to be an important determinant for binding within a putative flat, cleftlike catalytic cavity. Bicyclic analogues were prepared using the naphthalene, quinoline, isoquinoline, and 2-iminochromene ring systems and examined for their ability to inhibit autophosphorylation of immunopurified p56lck. The most potent analogues were methyl 7,8-dihydroxyisoquinoline-3-carboxylate (12) (IC50 = 0.2 muM) and 7,8-dihydroxyisoquinoline-3-carboxamide (13) (IC50 = 0.5 muM). Inhibition by 12 was not competitive with respect to ATP. These compounds may represent important new structural motifs for the development of p56lck inhibitors.

  DOI：

  10.1021/jm00056a001

文献信息

• Burke (Jr) Terrence R., Lim Benjamin, Marquez Victor E., Li Zhen-Hong, Bo+, J. Med. Chem., 36 (1993) N 4, S 425-432
  作者：Burke (Jr) Terrence R., Lim Benjamin, Marquez Victor E., Li Zhen-Hong, Bo+

  DOI：——

  日期：——
• Bicyclic compounds as ring-constrained inhibitors of protein-tyrosine kinase p56lck
  作者：Terrence R. Burke、Benjamin Lim、Victor E. Marquez、Zhen Hong Li、Joseph B. Bolen、Irena Stefanova、Ivan D. Horak

  DOI：10.1021/jm00056a001

  日期：1993.2

  A study was undertaken to prepare inhibitors of the lymphocyte protein-tyrosine kinase p56lck. Using the known p56lck inhibitor 3,4-dihydroxy-alpha-cyanocinnamamide (4) as a lead compound, bicyclic analogues were designed as conformationally constrained mimetics in which the phenyl ring and vinyl side chain of the cinnamamide are locked into a coplanar orientation. Such planarity was rationalized to be an important determinant for binding within a putative flat, cleftlike catalytic cavity. Bicyclic analogues were prepared using the naphthalene, quinoline, isoquinoline, and 2-iminochromene ring systems and examined for their ability to inhibit autophosphorylation of immunopurified p56lck. The most potent analogues were methyl 7,8-dihydroxyisoquinoline-3-carboxylate (12) (IC50 = 0.2 muM) and 7,8-dihydroxyisoquinoline-3-carboxamide (13) (IC50 = 0.5 muM). Inhibition by 12 was not competitive with respect to ATP. These compounds may represent important new structural motifs for the development of p56lck inhibitors.
• 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.