5-[(E)-2-cyclopropyl-2-(2'-methoxyphenyl)vinyl]furo-[2,3-d]pyrimidine-2,4-diamine | 1196851-96-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃[2,3-d]嘧啶
• 英文名称: 5-[(E)-2-cyclopropyl-2-(2'-methoxyphenyl)vinyl]furo-[2,3-d]pyrimidine-2,4-diamine
• 英文别名: 5-[(E)-2-Cyclopropyl-2-(2-Methoxyphenyl)ethenyl]furo[2,3-D]pyrimidine-2,4-Diamine
• CAS: 1196851-96-3
• 化学式: C₁₈H₁₈N₄O₂
• 分子量: 322.367
• InChiKey: PUOLMVSSUQSKAQ-MDWZMJQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  100
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-氯甲基呋喃并[2,3-d]嘧啶-2,4-二胺 、 环丙基(2-甲氧基苯基)甲酮 在 三丁基膦 、 sodium hydride 作用下， 以 二甲基亚砜 、 mineral oil 为溶剂， 反应 3.0h， 生成 5-[(Z)-2-cyclopropyl-2-(2'-methoxyphenyl)vinyl]furo-[2,3-d]pyrimidine-2,4-diamine 、 5-[(E)-2-cyclopropyl-2-(2'-methoxyphenyl)vinyl]furo-[2,3-d]pyrimidine-2,4-diamine
  参考文献：
  名称：

  Design, synthesis, and X-ray crystal structures of 2,4-diaminofuro[2,3-d]pyrimidines as multireceptor tyrosine kinase and dihydrofolate reductase inhibitors

  摘要：

  To optimize dual receptor tyrosine kinase (RTK) and dihydrofolate reductase ( DHFR) inhibition, the E-and Z-isomers of 5-[2-(2-methoxyphenyl)prop-1-en-1-yl]furo[2,3-d]pyrimidine-2,4-diamines (1a and 1b) were separated by HPLC and the X-ray crystal structures (2.0 and 1.4 angstrom, respectively) with mouse DHFR and NADPH as well as 1b with human DHFR (1.5 angstrom) were determined. The E- and Z-isomers adopt different binding modes when bound to mouse DHFR. A series of 2,4-diaminofuro[2,3-d]pyrimidines 2-13 were designed and synthesized using the X-ray crystal structures of 1a and 1b with DHFR to increase their DHFR inhibitory activity. Wittig reactions of appropriate 2-methoxyphenyl ketones with 2,4-diamino-6-chloromethyl furo[2,3-d]pyrimidine afforded the C8-C9 unsaturated compounds 2-7 and catalytic reduction gave the saturated 8-13. Homologation of the C9-methyl analog maintains DHFR inhibitory activity. In addition, inhibition of EGFR and PDGFR-beta were discovered for saturated C9-homologated analogs 9 and 10 that were absent in the saturated C9-methyl analogs. (c) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.08.044

文献信息

• Design, synthesis, and X-ray crystal structures of 2,4-diaminofuro[2,3-d]pyrimidines as multireceptor tyrosine kinase and dihydrofolate reductase inhibitors
  作者：Aleem Gangjee、Wei Li、Lu Lin、Yibin Zeng、Michael Ihnat、Linda A. Warnke、Dixy W. Green、Vivian Cody、Jim Pace、Sherry F. Queener

  DOI：10.1016/j.bmc.2009.08.044

  日期：2009.10

  To optimize dual receptor tyrosine kinase (RTK) and dihydrofolate reductase ( DHFR) inhibition, the E-and Z-isomers of 5-[2-(2-methoxyphenyl)prop-1-en-1-yl]furo[2,3-d]pyrimidine-2,4-diamines (1a and 1b) were separated by HPLC and the X-ray crystal structures (2.0 and 1.4 angstrom, respectively) with mouse DHFR and NADPH as well as 1b with human DHFR (1.5 angstrom) were determined. The E- and Z-isomers adopt different binding modes when bound to mouse DHFR. A series of 2,4-diaminofuro[2,3-d]pyrimidines 2-13 were designed and synthesized using the X-ray crystal structures of 1a and 1b with DHFR to increase their DHFR inhibitory activity. Wittig reactions of appropriate 2-methoxyphenyl ketones with 2,4-diamino-6-chloromethyl furo[2,3-d]pyrimidine afforded the C8-C9 unsaturated compounds 2-7 and catalytic reduction gave the saturated 8-13. Homologation of the C9-methyl analog maintains DHFR inhibitory activity. In addition, inhibition of EGFR and PDGFR-beta were discovered for saturated C9-homologated analogs 9 and 10 that were absent in the saturated C9-methyl analogs. (c) 2009 Elsevier Ltd. All rights reserved.