3-(2,4-diaminopyrimido[4,5-b]pyrazin-6-yl)-2-(3-carbomethoxypyrid-6-yl)-propionic acid methyl ester | 154586-71-7

• 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: 3-(2,4-diaminopyrimido[4,5-b]pyrazin-6-yl)-2-(3-carbomethoxypyrid-6-yl)-propionic acid methyl ester
• 英文别名: Methyl 6-[3-(2,4-diaminopteridin-6-yl)-1-methoxy-1-oxopropan-2-yl]pyridine-3-carboxylate
• CAS: 154586-71-7
• 化学式: C₁₇H₁₇N₇O₄
• 分子量: 383.366
• InChiKey: NSCSLTXOPKVMRH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 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：

  3-(2,4-diaminopyrimido[4,5-b]pyrazin-6-yl)-2-(3-carbomethoxypyrid-6-yl)-propionic acid methyl ester 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 4.17h， 生成
  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：

  6-(Carboxymethyl)pyridine-3-carboxylic acid 在 盐酸 、 sodium hydride 作用下， 反应 75.5h， 生成 3-(2,4-diaminopyrimido[4,5-b]pyrazin-6-yl)-2-(3-carbomethoxypyrid-6-yl)-propionic acid methyl 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

文献信息

• Heteroaroyl 10-deazaamino-pterine compounds and use for rheumatoid
  申请人：SRI International

  公开号：US05354751A1

  公开（公告）日：1994-10-11

  There is disclosed certain heteroaroyl 10-deazaaminopterin and 5, 10 and 8, 10 di deazaminopterin compounds and their use for treatment of rheumatoid arthritis and related diseases and preparative process. Also disclosed are 10 alkenyl-(and alkynyl) 10-deazaminopterins also disclosed for treatment of rheumatoid arthritis and for leukemia and ascites tumors and preparative process.

  本文披露了某些异芳基10-脱氨甲葉酸和5、10以及8、10二脱氨甲葉酸化合物及其用于治疗类风湿性关节炎和相关疾病的方法和制备过程。同时还披露了用于治疗类风湿性关节炎、白血病和腹水瘤的10烯基-(和炔基)10-脱氨甲葉酸化合物及其制备过程。
• US5354751A
  申请人：——

  公开号：US5354751A

  公开（公告）日：1994-10-11
• [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.
• Analogues of Methotrexate in Rheumatoid Arthritis. 1. Effects of 10-Deazaaminopterin Analogues on Type II Collagen-Induced Arthritis in Mice
  作者：Joseph I. DeGraw、William T. Colwell、Jac Crase、R. Lane Smith、James R. Piper、William R. Waud、Francis M. Sirotnak

  DOI：10.1021/jm9505526

  日期：1997.1.1

  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.