2,4-diamino-5-methyl-6-(2,5-dimethoxybenzyl)-7-oxo-7,8-dihydropyrido[2,3-d ]pyrimidine | 72676-84-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 2,4-diamino-5-methyl-6-(2,5-dimethoxybenzyl)-7-oxo-7,8-dihydropyrido[2,3-d ]pyrimidine
• 英文别名: 2,4-diamino-7,8-dihydro-6-(2,5-dimethoxybenzyl)-5-methyl-7-oxopyrido<2,3-d>pyrimidine；2,4,-diamino-5-methyl-6-(2,5-dimethoxybenzyl)-7-oxo-7,8-dihydropyrido[2,3-d ]pyrimidine；2,4-diamino-5-methyl-6-(2,5-dimethoxybenzyl)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidine；2,4-diamino-7,8-dihydro-6-(2,5-dimethoxybenzyl)-5-methyl-7-oxopyrido[2,3-d]pyrimidine；2,4-diamino-6-[(2,5-dimethoxyphenyl)methyl]-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one
• CAS: 72676-84-7
• 化学式: C₁₇H₁₉N₅O₃
• 分子量: 341.37
• InChiKey: GRFQELAZTJFQRC-UHFFFAOYSA-N

物化性质

• 熔点：
  325-326 °C
• 沸点：
  536.4±60.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  125
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2,4-diamino-5-methyl-6-(2,5-dimethoxybenzyl)-7-oxo-7,8-dihydropyrido[2,3-d ]pyrimidine 在 palladium on activated charcoal 氢氧化钾 、 N,N-dimethylformamide, thionyl chloride 、 氢气 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 39.0h， 生成 吡曲克辛
  参考文献：
  名称：

  Synthesis and antitumor activity of 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methylpyrido[2,3-d]pyrimidine

  摘要：

  The synthesis of 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methylpyrido[2,3-d]pyrimidine (BW301U, 7) by a route that has general applicability to the preparation of many 6-(substituted benzyl)-5-methylpyrido[2,3-d]pyrimidines is described. The key intermediate, 2,4-diamino-7,8-dihydro-6-(2,5-dimethoxybenzyl)-5-methyl-7-oxopyrido[2,3-d]pyrimidine (4), is converted to the 7-chloro compound 5 by treatment with a 1:1 complex of N,N-dimethylformamide--thionyl chloride, and 5 is hydrogenolyzed with palladium on charcoal in the presence of potassium hydroxide to yield 7. BW301U is a potent lipid-soluble inhibitor of mammalian dihydrofolate reductase and has significant activity against the Walker 256 carcinosarcoma in rats.

  DOI：

  10.1021/jm00177a025
• 作为产物：
  描述：

  ethyl α-(2,5-dimethoxybenzylidene)acetoacetate 在 palladium on activated charcoal 氢气 作用下， 以 二苯醚 、 乙酸乙酯 为溶剂， 195.0~230.0 ℃ 、275.79 kPa 条件下， 反应 3.5h， 生成 2,4-diamino-5-methyl-6-(2,5-dimethoxybenzyl)-7-oxo-7,8-dihydropyrido[2,3-d ]pyrimidine
  参考文献：
  名称：

  Synthesis and antitumor activity of 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methylpyrido[2,3-d]pyrimidine

  摘要：

  The synthesis of 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methylpyrido[2,3-d]pyrimidine (BW301U, 7) by a route that has general applicability to the preparation of many 6-(substituted benzyl)-5-methylpyrido[2,3-d]pyrimidines is described. The key intermediate, 2,4-diamino-7,8-dihydro-6-(2,5-dimethoxybenzyl)-5-methyl-7-oxopyrido[2,3-d]pyrimidine (4), is converted to the 7-chloro compound 5 by treatment with a 1:1 complex of N,N-dimethylformamide--thionyl chloride, and 5 is hydrogenolyzed with palladium on charcoal in the presence of potassium hydroxide to yield 7. BW301U is a potent lipid-soluble inhibitor of mammalian dihydrofolate reductase and has significant activity against the Walker 256 carcinosarcoma in rats.

  DOI：

  10.1021/jm00177a025

文献信息

• Treatment with dialkoxy pyridopyrimidines
  申请人：Burroughs Wellcome Co.

  公开号：US04372957A1

  公开（公告）日：1983-02-08

  Potent psoriasis activity in combination with low inhibition of histamine N-methyltransferase has been found in a class of 2,4-diamino-6-(2,5-dialkoxybenzyl)-5-methylpyrido[2,3-d]pyrimidines.

  在一类2,4-二氨基-6-(2,5-二烷氧基苯基)-5-甲基吡啶并[2,3-d]嘧啶中发现了强烈的银屑病活性，同时对组胺N-甲基转移酶的抑制作用较低。
• Dialkoxy pyridopyrimidine compounds
  申请人：Burroughs Wellcome Co.

  公开号：US04959474A1

  公开（公告）日：1990-09-25

  A novel class of 2,4-diamino-6-(2,5-dialkoxybenzyl)-5-methyl[2,3-d]-pyrimidines is described. These compounds are antibacterial agents, active against certain Streptococcus species. They are also active antiproliferative agents.

  介绍了一类新型的2,4-二氨基-6-(2,5-二烷氧基苯基)-5-甲基[2,3-d]-嘧啶类化合物。这些化合物是抗菌剂，对某些链球菌物种具有活性。它们还是活性抗增殖剂。
• Treatment of disease
  申请人：——

  公开号：US04818759A1

  公开（公告）日：1989-04-04

  A method of treatment of rheumatoid arthritis in humans in need thereof which comprises administering to said human an effective rheumatoid arthritis treatment amount of compound 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methylpyrido[2,3-d]pyrimidine or pharmaceutically acceptable acid addition salt thereof.

  一种治疗风湿性关节炎的方法，适用于需要治疗的人类，包括给予该人类有效的风湿性关节炎治疗剂量的化合物2,4-二氨基-6-(2,5-二甲氧基苯基)-5-甲基吡咯[2,3-d]嘧啶或其药学上可接受的酸加盐。
• Alkoxybenzylpyridopyrimidines, methods for their preparation and pharmaceutical formulations thereof
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0021292A1

  公开（公告）日：1981-01-07

  Compounds of the formula (II): ( where Ar is and R and R' are lower (C1-6) alkyl and acid addition salts thereof, methods for the preparation thereof, formulations thereof and the use thereof as therapeutic agents, in particular as antiproliferative agents, are disclosed.

  本发明公开了式(II)：（ 其中 Ar 为，R 和 R' 为低级（C1-6）烷基）的化合物及其酸加成盐、其制备方法、其制剂以及其作为治疗剂，特别是作为抗增殖剂的用途。
• Medicaments for the treatment of rheumatoid arthritis
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0279565B1

  公开（公告）日：1992-01-02