2-{4-[2-(2,4-Diamino-pteridin-6-yl)-butyl]-benzoylamino}-pentanedioic acid | 122622-74-6

• 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: 2-{4-[2-(2,4-Diamino-pteridin-6-yl)-butyl]-benzoylamino}-pentanedioic acid
• 英文别名: 2-[[4-[2-(2,4-diaminopteridin-6-yl)butyl]benzoyl]amino]pentanedioic acid
• CAS: 122622-74-6
• 化学式: C₂₂H₂₅N₇O₅
• 分子量: 467.484
• InChiKey: BRBJBKGSGUBGLP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  207
• 氢给体数：
  5
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  4-((E)-2-Benzyloxycarbonyl-but-1-enyl)-benzoic acid methyl ester 在 palladium on activated charcoal 、 钯 2,4,6-三甲基吡啶 、 盐酸 、 sodium hydroxide 、 氯化亚砜 、 sodium azide 、 氢气 、 双氧水 、 溶剂黄146 、 三乙胺 、 锌 、 氯甲酸异丁酯 作用下， 以 甲醇 、 乙醇 、 乙二醇甲醚 、 水 、 N,N-二甲基甲酰胺 、 异丙醇 、 苯 为溶剂， 生成 2-{4-[2-(2,4-Diamino-pteridin-6-yl)-butyl]-benzoylamino}-pentanedioic acid
  参考文献：
  名称：

  Synthesis and antifolate properties of 9-alkyl-10-deazaminopterins

  摘要：

  Reformatski condensation of benzyl 2-bromopropionate with 4-carbomethoxybenzaldehyde, followed by dehydration afforded benzyl 2-methyl-p-carbomethoxycinnamate (4a). Hydrogenation over a Pd catalyst gave the hydrocinnamic acid 5a. Conversion to the chloromethyl (6a) and azidomethyl ketone (7a) was followed by hydrogenation to the aminomethyl ketone (8a). Direct N-alkylation by 2,4-diamino-5-nitro-6-chloropyrimidine followed by reductive ring closure in Zn-HOAc and subsequent saponification of the benzoate ester yielded 4-amino-4-deoxy-9-methyl-10-deazapteroic acid (11a). Coupling with diethyl L-glutamate and saponification afforded 9-methyl-10-deazaminopterin (13a). The 9-ethyl analogue (13b) was similarly prepared from benzyl 2-bromobutyrate. The 9-methyl analogue (13a) was 21 times more potent than MTX as an inhibitor of cell growth in L1210 cells. The reason for this enhanced cytotoxicity in L1210 is unclear, since enzyme inhibition and transport parameters were similar to those of MTX. In human Manca leukemia cells growth inhibition was not dramatic and paralleled MTX.

  DOI：

  10.1021/jm00163a035

文献信息

• Synthesis and antifolate properties of 9-alkyl-10-deazaminopterins
  作者：Joseph I. DeGraw、Pamela H. Christie、Roy L. Kisliuk、Yvette Gaumont、Francis M. Sirotnak

  DOI：10.1021/jm00163a035

  日期：1990.1

  Reformatski condensation of benzyl 2-bromopropionate with 4-carbomethoxybenzaldehyde, followed by dehydration afforded benzyl 2-methyl-p-carbomethoxycinnamate (4a). Hydrogenation over a Pd catalyst gave the hydrocinnamic acid 5a. Conversion to the chloromethyl (6a) and azidomethyl ketone (7a) was followed by hydrogenation to the aminomethyl ketone (8a). Direct N-alkylation by 2,4-diamino-5-nitro-6-chloropyrimidine followed by reductive ring closure in Zn-HOAc and subsequent saponification of the benzoate ester yielded 4-amino-4-deoxy-9-methyl-10-deazapteroic acid (11a). Coupling with diethyl L-glutamate and saponification afforded 9-methyl-10-deazaminopterin (13a). The 9-ethyl analogue (13b) was similarly prepared from benzyl 2-bromobutyrate. The 9-methyl analogue (13a) was 21 times more potent than MTX as an inhibitor of cell growth in L1210 cells. The reason for this enhanced cytotoxicity in L1210 is unclear, since enzyme inhibition and transport parameters were similar to those of MTX. In human Manca leukemia cells growth inhibition was not dramatic and paralleled MTX.