2,6-diamino-3,4-dihydro-4-oxopyrido<2,3-d>pyrimidine | 91996-79-1

• 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: 2,6-diamino-3,4-dihydro-4-oxopyrido<2,3-d>pyrimidine
• 英文别名: 2,6-Diaminopyrido[2,3-d]pyrimidin-4(1h)-one；2,6-diamino-3H-pyrido[2,3-d]pyrimidin-4-one
• CAS: 91996-79-1
• 化学式: C₇H₇N₅O
• 分子量: 177.165
• InChiKey: LTDDWSHVWVLMOE-UHFFFAOYSA-N

物化性质

• 密度：
  1.90±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  106
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,6-diamino-3,4-dihydro-4-oxopyrido<2,3-d>pyrimidine 在 3 A molecular sieve 、 硼烷-叔丁基胺 、 溶剂黄146 、 三氟乙酸 作用下， 反应 24.0h， 生成 (2S)-2-[[4-[[(2-氨基-4-氧代-1H-吡啶并[5,6-e]嘧啶-6-基)氨基]甲基]苯甲酰基]氨基]戊烷二酸
  参考文献：
  名称：

  Synthesis and biological evaluation of 5-deazaisofolic acid, 5-deaza-5,6,7,8-tetrahydroisofolic acid, and their N9-substituted analogues

  摘要：

  Prompted by recent disclosures concerning the potent antitumor activities of 5-deaza-5,6,7,8-tetrahydrofolic acid and 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF), we have prepared 5-deazaisofolic acid (3a) and 5-deaza-5,6,7,8-tetrahydroisofolic acid (4a). Reductive condensation of 2,6-diamino-3,4-dihydro-4-oxopyrido[2,3-d]pyrimidine with di-tert-butyl N-(4-formylbenzoyl)-L-glutamate and subsequent deprotection with trifluoroacetic acid yielded 5-deazaisofolic acid in good yield. Catalytic hydrogenation of this analogue then gave 4a. The 9-CH3 and 9-CHO modifications of 3a and the 9-CH3 derivative of 4a were also synthesized. Each of the new analogues was evaluated with a variety of folate-requiring enzymes as well as MCF-7 cells in culture. Compound 4a had an IC50 of ca. 1-mu-M against MCF-7 cells and was nearly 100-fold less potent than DDATHF in this regard. The three oxidized isofolate analogues were all poor inhibitors of tumor cell growth.

  DOI：

  10.1021/jm00106a021
• 作为产物：
  描述：

  2-amino-3,4-dihydro-4-oxo-6-nitropyrido<2,3-d>pyrimidine hydrochloride 在 palladium on activated charcoal 氢气 作用下， 以 乙二醇甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以78%的产率得到2,6-diamino-3,4-dihydro-4-oxopyrido<2,3-d>pyrimidine
  参考文献：
  名称：

  Synthesis and biological evaluation of 5-deazaisofolic acid, 5-deaza-5,6,7,8-tetrahydroisofolic acid, and their N9-substituted analogues

  摘要：

  Prompted by recent disclosures concerning the potent antitumor activities of 5-deaza-5,6,7,8-tetrahydrofolic acid and 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF), we have prepared 5-deazaisofolic acid (3a) and 5-deaza-5,6,7,8-tetrahydroisofolic acid (4a). Reductive condensation of 2,6-diamino-3,4-dihydro-4-oxopyrido[2,3-d]pyrimidine with di-tert-butyl N-(4-formylbenzoyl)-L-glutamate and subsequent deprotection with trifluoroacetic acid yielded 5-deazaisofolic acid in good yield. Catalytic hydrogenation of this analogue then gave 4a. The 9-CH3 and 9-CHO modifications of 3a and the 9-CH3 derivative of 4a were also synthesized. Each of the new analogues was evaluated with a variety of folate-requiring enzymes as well as MCF-7 cells in culture. Compound 4a had an IC50 of ca. 1-mu-M against MCF-7 cells and was nearly 100-fold less potent than DDATHF in this regard. The three oxidized isofolate analogues were all poor inhibitors of tumor cell growth.

  DOI：

  10.1021/jm00106a021

文献信息

• Synthesis and biological evaluation of 5-deazaisofolic acid, 5-deaza-5,6,7,8-tetrahydroisofolic acid, and their N9-substituted analogues
  作者：Shyam K. Singh、Inderjit K. Dev、David S. Duch、Robert Ferone、Gary K. Smith、James H. Freisheim、John B. Hynes

  DOI：10.1021/jm00106a021

  日期：1991.2

  Prompted by recent disclosures concerning the potent antitumor activities of 5-deaza-5,6,7,8-tetrahydrofolic acid and 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF), we have prepared 5-deazaisofolic acid (3a) and 5-deaza-5,6,7,8-tetrahydroisofolic acid (4a). Reductive condensation of 2,6-diamino-3,4-dihydro-4-oxopyrido[2,3-d]pyrimidine with di-tert-butyl N-(4-formylbenzoyl)-L-glutamate and subsequent deprotection with trifluoroacetic acid yielded 5-deazaisofolic acid in good yield. Catalytic hydrogenation of this analogue then gave 4a. The 9-CH3 and 9-CHO modifications of 3a and the 9-CH3 derivative of 4a were also synthesized. Each of the new analogues was evaluated with a variety of folate-requiring enzymes as well as MCF-7 cells in culture. Compound 4a had an IC50 of ca. 1-mu-M against MCF-7 cells and was nearly 100-fold less potent than DDATHF in this regard. The three oxidized isofolate analogues were all poor inhibitors of tumor cell growth.