Methyl 5-[1-benzhydryloxy-3-(2,4-diaminopteridin-6-yl)-1-oxopropan-2-yl]pyridine-2-carboxylate | 154586-81-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Methyl 5-[1-benzhydryloxy-3-(2,4-diaminopteridin-6-yl)-1-oxopropan-2-yl]pyridine-2-carboxylate
• CAS: 154586-81-9
• 化学式: C₂₉H₂₅N₇O₄
• 分子量: 535.562
• InChiKey: QSLLFNBQPCGYAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  169
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  Methyl 5-[1-benzhydryloxy-3-(2,4-diaminopteridin-6-yl)-1-oxopropan-2-yl]pyridine-2-carboxylate 在 sodium hydroxide 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙二醇甲醚 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.33h， 生成 (2S)-2-[[5-[2-(2,4-diaminopteridin-6-yl)ethyl]pyridine-2-carbonyl]amino]pentanedioic acid
  参考文献：
  名称：

  Analogues of Methotrexate in Rheumatoid Arthritis. 1. Effects of 10-Deazaaminopterin Analogues on Type II Collagen-Induced Arthritis in Mice

  摘要：

  Carbonation of the dianions (LDA) of 5-methylthiophene-2-carboxylic, 2-methylpyridine-5-carboxylic, and 3-methylpyridine-6-carboxylic acids provided the respective carboxy heteroarylacetic acids. The crude diacids were directly esterified in MeOH-HCl to afford the diesters. Alkylation of the sodio anions with ethyl iodide yielded the appropriate a-ethyl diesters. The anions of the various diester substrates were then alkylated by 2,4-diamino-6-(bromomethyl)-pteridine followed by ester saponification at room temperature to afford the respective 2,4-diamino-4-deoxy-10-carboxy-10-deazapteroic acids. The 10-carboxyl group was readily decarboxylated by heating in DMSO at temperatures of 110-135 degrees C to give the diamino 10-deaza heteropteroic acid intermediates. Coupling with diethyl L-glutamate followed by ester hydrolysis afforded the target aminopterins. The analogues were evaluated for antiinflammatory effect in the mouse type II collagen model. The thiophene analogue of 10-ethyl-10-deazaaminopterin was found to be an effective inhibitor in terms of reduced visual evidence of inflammation and swelling as determined by caliper measurement.

  DOI：

  10.1021/jm9505526
• 作为产物：
  描述：

  5-甲基-2-甲酸吡啶 在 盐酸 、 氢氧化钾 、 sodium hydride 、 lithium diisopropyl amide 作用下， 反应 105.5h， 生成 Methyl 5-[1-benzhydryloxy-3-(2,4-diaminopteridin-6-yl)-1-oxopropan-2-yl]pyridine-2-carboxylate
  参考文献：
  名称：

  Analogues of Methotrexate in Rheumatoid Arthritis. 1. Effects of 10-Deazaaminopterin Analogues on Type II Collagen-Induced Arthritis in Mice

  摘要：

  Carbonation of the dianions (LDA) of 5-methylthiophene-2-carboxylic, 2-methylpyridine-5-carboxylic, and 3-methylpyridine-6-carboxylic acids provided the respective carboxy heteroarylacetic acids. The crude diacids were directly esterified in MeOH-HCl to afford the diesters. Alkylation of the sodio anions with ethyl iodide yielded the appropriate a-ethyl diesters. The anions of the various diester substrates were then alkylated by 2,4-diamino-6-(bromomethyl)-pteridine followed by ester saponification at room temperature to afford the respective 2,4-diamino-4-deoxy-10-carboxy-10-deazapteroic acids. The 10-carboxyl group was readily decarboxylated by heating in DMSO at temperatures of 110-135 degrees C to give the diamino 10-deaza heteropteroic acid intermediates. Coupling with diethyl L-glutamate followed by ester hydrolysis afforded the target aminopterins. The analogues were evaluated for antiinflammatory effect in the mouse type II collagen model. The thiophene analogue of 10-ethyl-10-deazaaminopterin was found to be an effective inhibitor in terms of reduced visual evidence of inflammation and swelling as determined by caliper measurement.

  DOI：

  10.1021/jm9505526