5-(5,6-dimethoxy-2,3-dihydro-1H-inden-1-ylidene)barbituric acid | 131010-57-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 5-(5,6-dimethoxy-2,3-dihydro-1H-inden-1-ylidene)barbituric acid
• 英文别名: 5-(5,6-Dimethoxy-2,3-dihydroinden-1-ylidene)-1,3-diazinane-2,4,6-trione
• CAS: 131010-57-6
• 化学式: C₁₅H₁₄N₂O₅
• 分子量: 302.287
• InChiKey: GMYXVINQLWJASW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  93.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(5,6-dimethoxy-2,3-dihydro-1H-inden-1-ylidene)barbituric acid 在 sodium tetrahydroborate 、 N,N-二乙基苯胺 、 三氯氧磷 作用下， 以 异丙醇 为溶剂， 反应 33.0h， 生成 2,4,6-trichloro-5-(5,6-dimethoxy-2,3-dihydro-1H-inden-1-yl)pyrimidine
  参考文献：
  名称：

  2,4-Diamino-5-benzylpyrimidines as antibacterial agents. 14. 2,3-Dihydro-1-(2,4-diamino-5-pyrimidyl)-1H-indenes as conformationally restricted analogs of trimethoprim

  摘要：

  A conformationally restricted analogue of trimethoprim (1a) has been prepared by connecting the ortho position of the benzene ring to the methylene linkage with two methylene groups, thus forming a dihydroindene derivative (2b). The chemistry involved the condensation of barbituric acid with an indanone derivative, followed by a three-step conversion to a 2,4-diaminopyrimidine. The S isomer of 2b was found to have a minimum-energy conformation very similar to that of 1a when bound to Escherichia coli dihydrofolate reductase, in contrast to that of 1a in vertebrate DHFR. Theoretically such a derivative might have increased specificity and activity against the bacterial enzyme. Molecular modeling experiments suggested that the actual decreased activity was due to crowding in the enzyme, caused by the extra atoms needed to restrict the conformation.

  DOI：

  10.1021/jm00106a011
• 作为产物：
  描述：

  巴比妥酸 、 5,6-二甲氧基茚酮 在 哌啶 作用下， 以 甲醇 为溶剂， 反应 72.0h， 以34%的产率得到5-(5,6-dimethoxy-2,3-dihydro-1H-inden-1-ylidene)barbituric acid
  参考文献：
  名称：

  2,4-Diamino-5-benzylpyrimidines as antibacterial agents. 14. 2,3-Dihydro-1-(2,4-diamino-5-pyrimidyl)-1H-indenes as conformationally restricted analogs of trimethoprim

  摘要：

  A conformationally restricted analogue of trimethoprim (1a) has been prepared by connecting the ortho position of the benzene ring to the methylene linkage with two methylene groups, thus forming a dihydroindene derivative (2b). The chemistry involved the condensation of barbituric acid with an indanone derivative, followed by a three-step conversion to a 2,4-diaminopyrimidine. The S isomer of 2b was found to have a minimum-energy conformation very similar to that of 1a when bound to Escherichia coli dihydrofolate reductase, in contrast to that of 1a in vertebrate DHFR. Theoretically such a derivative might have increased specificity and activity against the bacterial enzyme. Molecular modeling experiments suggested that the actual decreased activity was due to crowding in the enzyme, caused by the extra atoms needed to restrict the conformation.

  DOI：

  10.1021/jm00106a011

文献信息

• CHAN, JOSEPH H.;ROTH, BARBARA, J. MED. CHEM., 34,(1991) N, C. 350-355
  作者：CHAN, JOSEPH H.、ROTH, BARBARA

  DOI：——

  日期：——
• BARBITURIC ACID ANALOGS AS THERAPEUTIC AGENTS
  申请人：DE BELIN Y. Jackie

  公开号：US20080113993A1

  公开（公告）日：2008-05-15

  This invention pertains to active barbituric acid analogs which inhibit HIF-1 activity (e.g., the interaction between HIF-1$g(a) and p300) and thereby inhibit angiogenesis, tumorigenesis, and proliferative conditions, such as cancer. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HIF-1 activity, and to inhibit angiogenesis, tumorigenesis, and proliferative conditions, such as cancer.