5-[β-(2,4-diamino-6-pteridinyl)ethyl]thiophene-2-carboxylic acid | 153802-52-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 蝶啶及其衍生物
• 英文名称: 5-[β-(2,4-diamino-6-pteridinyl)ethyl]thiophene-2-carboxylic acid
• 英文别名: 5-[2-(2,4-Diaminopteridin-6-yl)ethyl]thiophene-2-carboxylic acid
• CAS: 153802-52-9
• 化学式: C₁₃H₁₂N₆O₂S
• 分子量: 316.343
• InChiKey: CUBDCRFQPCAVNQ-UHFFFAOYSA-N

物化性质

• 沸点：
  639.1±65.0 °C(Predicted)
• 密度：
  1.609±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  169
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5-[β-(2,4-diamino-6-pteridinyl)ethyl]thiophene-2-carboxylic acid 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.25h， 生成 diethyl (2S)-2-[[5-[2-(2,4-diaminopteridin-6-yl)ethyl]thiophene-2-carbonyl]amino]pentanedioate
  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-methoxy-2-oxoethyl)thiophene-2-carboxylate 在 sodium hydroxide 、 sodium hydride 作用下， 以 乙二醇甲醚 、 二甲基亚砜 为溶剂， 反应 5.75h， 生成 5-[β-(2,4-diamino-6-pteridinyl)ethyl]thiophene-2-carboxylic 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

文献信息

• US5374726A
  申请人：——

  公开号：US5374726A

  公开（公告）日：1994-12-20
• US5354751A
  申请人：——

  公开号：US5354751A

  公开（公告）日：1994-10-11
• US5536724A
  申请人：——

  公开号：US5536724A

  公开（公告）日：1996-07-16
• [EN] HETEROAROYL-10-DEAZAAMINOPTERINS FOR TREATMENT OF INFLAMMATION<br/>[FR] HETEROAROYL-10-DESAZAAMINOPTERINES POUR LE TRAITEMENT DES INFLAMMATIONS
  申请人：SRI INTERNATIONAL

  公开号：WO1993022315A1

  公开（公告）日：1993-11-11

  (EN) The invention relates to certain heteroaroyl-10-deazaaminopterin compounds, as well as a method and composition employing certain heteroaroyl-10-deazaaminopterin compounds for the treatment of inflammatory disease, such as rheumatoid arthritis.(FR) L'invention concerne certaines hétéroaroyl-10-désazaaminoptérines ainsi qu'un procédé et une composition utilisant certaines hétéroaroyl-10-désazaaminoptérines pour le traitement de maladies inflammatoires telles que la polyarthrite rhumatoïde.