diethyl 2-acetyl-5-deazaisofolate | 130327-74-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: diethyl 2-acetyl-5-deazaisofolate
• 英文别名: diethyl (2S)-2-[[4-[[(2-acetamido-4-oxo-1H-pyrido[2,3-d]pyrimidin-6-yl)amino]methyl]benzoyl]amino]pentanedioate
• CAS: 130327-74-1
• 化学式: C₂₆H₃₀N₆O₇
• 分子量: 538.56
• InChiKey: IFGCTAVSPQVFRQ-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.89
• 重原子数：
  39.0
• 可旋转键数：
  12.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  181.47
• 氢给体数：
  4.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  diethyl 2-acetyl-5-deazaisofolate 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 以68.6%的产率得到(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：

  N-(6-nitro-4-oxo-1H-pyrido[2,3-d]pyrimidin-2-yl)acetamide 在 palladium on activated charcoal 、 镍 氢气 、 溶剂黄146 作用下， 以 乙二醇甲醚 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、386.11 kPa 条件下， 反应 18.5h， 生成 diethyl 2-acetyl-5-deazaisofolate
  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