(S)-2-({5-[1-(2,4-Diamino-pteridin-6-ylmethyl)-propyl]-thiophene-2-carbonyl}-amino)-pentanedioic acid diethyl ester | 154586-68-2

• 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: (S)-2-({5-[1-(2,4-Diamino-pteridin-6-ylmethyl)-propyl]-thiophene-2-carbonyl}-amino)-pentanedioic acid diethyl ester
• 英文别名: diethyl (2S)-2-[[5-[1-(2,4-diaminopteridin-6-yl)butan-2-yl]thiophene-2-carbonyl]amino]pentanedioate
• CAS: 154586-68-2
• 化学式: C₂₄H₃₁N₇O₅S
• 分子量: 529.62
• InChiKey: SBKSGXKHDHFLEH-WUJWULDRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  37
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  214
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (S)-2-({5-[1-(2,4-Diamino-pteridin-6-ylmethyl)-propyl]-thiophene-2-carbonyl}-amino)-pentanedioic acid diethyl ester 在 sodium hydroxide 作用下， 以 乙二醇甲醚 为溶剂， 反应 1.0h， 生成 (S)-2-({5-[1-(2,4-Diamino-pteridin-6-ylmethyl)-propyl]-thiophene-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：

  Methyl 5-[2-[(2,4-diaminopteridin-6-yl)methyl]-1-methoxy-1-oxobutan-2-yl]thiophene-2-carboxylate 在 sodium hydroxide 、 三乙胺 作用下， 以 乙二醇甲醚 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.25h， 生成 (S)-2-({5-[1-(2,4-Diamino-pteridin-6-ylmethyl)-propyl]-thiophene-2-carbonyl}-amino)-pentanedioic acid diethyl ester
  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