2,4-diamino-5-methyl-6-(2,5-dimethoxybenzyl)-7-chloro-pyrido[2,3-d]pyrimidine | 72676-85-8

• 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-chloro-pyrido[2,3-d]pyrimidine
• 英文别名: 7-chloro-2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methylpyrido<2,3-d>pyrimidine；2,4-diamino-5-methyl-6-(2,5-dimethoxybenzyl)-7-chloropyrido[2,3-d ]pyrimidine；7-chloro-2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methylpyrido[2,3-d]pyrimidine；2,4-Diamino-5-methyl-6-(2,5-dimethoxybenzyl)-7-chloropyrido[2,3-d]pyrimidine；7-chloro-6-[(2,5-dimethoxyphenyl)methyl]-5-methylpyrido[2,3-d]pyrimidine-2,4-diamine
• CAS: 72676-85-8
• 化学式: C₁₇H₁₈ClN₅O₂
• 分子量: 359.815
• InChiKey: LSSHHTHBNRKDQH-UHFFFAOYSA-N

物化性质

• 沸点：
  622.5±65.0 °C(Predicted)
• 密度：
  1.365±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 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：
  109
• 氢给体数：
  2
• 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-chloro-pyrido[2,3-d]pyrimidine 在 palladium on activated charcoal 氢氧化钾 、 氢气 作用下， 以 乙醇 为溶剂， 反应 36.0h， 以38%的产率得到吡曲克辛
  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：

  2,4-diamino-5-methyl-6-(2,5-dimethoxybenzyl)-7-oxo-7,8-dihydropyrido[2,3-d ]pyrimidine 在 N,N-dimethylformamide, thionyl chloride 作用下， 以 氯仿 为溶剂， 反应 3.0h， 以40%的产率得到2,4-diamino-5-methyl-6-(2,5-dimethoxybenzyl)-7-chloro-pyrido[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

• 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。
• 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.

  一类2,4-二氨基-6-(2,5-二烷氧基苯基)-5-甲基吡啶[2,3-d]嘧啶化合物表现出强的银屑病活性，同时对组胺N-甲基转移酶的抑制作用较低。
• 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
• J. Med. Chem. 1980, 23, 327-329
  作者：

  DOI：——

  日期：——