5--N-methylamino>thenoic acid | 138899-69-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 5--N-methylamino>thenoic acid
• 英文别名: 2-[N-(2-methyl-4-oxoquinazoline-6-methyl)-N-methyl]aminothiophene-2-carboxylic acid；5-(((3,4-dihydro-2-methyl-4-oxo-6-quinazolinyl)methyl)methylamino)-2-thiophene-carboxylic acid；5-(((3,4-Dihydro-2-methyl-4-oxo-6-quinazolinyl)methyl)methylamino)-2-thiophene-carboxylic acid；5-[methyl-[(2-methyl-4-oxo-3H-quinazolin-6-yl)methyl]amino]thiophene-2-carboxylic acid
• CAS: 138899-69-1
• 化学式: C₁₆H₁₅N₃O₃S
• 分子量: 329.379
• InChiKey: ZHQMWRFNBFKOLR-UHFFFAOYSA-N

物化性质

• 沸点：
  606.5±65.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5--N-methylamino>thenoic acid 在 diethyl cyanophosphoridate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 (2S)-2-[[(4S)-4-carboxy-4-[[5-[methyl-[(2-methyl-4-oxo-1H-quinazolin-6-yl)methyl]amino]thiophene-2-carbonyl]amino]butanoyl]amino]pentanedioic acid;2,2,2-trifluoroacetic acid
  参考文献：
  名称：

  Syntheses and thymidylate synthase inhibitory activity of the poly-.gamma.-glutamyl conjugates of N-[5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino]-2-thenoyl]-L-glutamic acid (ICI D1694) and other quinazoline antifolates

  摘要：

  Thirteen poly-gamma-glutamates derived from several novel antifolates have been synthesized by a convergent route. The syntheses of poly-gamma-glutamyl conjugates of N-[5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino]-2-thenoyl]-L-glutamic acid (8) (ICI D1694), 2-desamino-N10-propargyl-5,8-dideazafolic acid (6), 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (7), 2-desamino-2-methyl-N10-propargyl-2'-fluoro-5,8-dideazafolic acid (9), and 2-desamino-2-methyl-4-chloro-N10-propargyl-2'-fluoro-3,5,8-trideazafolic acid (11) are described. A key step in the route involves coupling of an alpha-tert-butyl-protected poly-gamma-glutamate of the required chain length to the appropriate 5,8-dideazapteroic acid, obtained by carboxypeptidase G2 cleavage of the parent monoglutamate, if available, or by chemical synthesis. Deprotection with trifluoroacetic acid in the final step gave the desired poly-gamma-glutamyl antifolates as their trifluoroacetate salts. As inhibitors of thymidylate synthase, these polyglutamates were more potent in every case than the corresponding non-polyglutamylated drug.

  DOI：

  10.1021/jm00083a008
• 作为产物：
  描述：

  雷替曲塞 在 Tris buffer (tris(hydroxymethyl)aminomethane, ZnCl₂, aq. HCl, pH 7.3) 作用下， 反应 2.0h， 以94%的产率得到5--N-methylamino>thenoic acid
  参考文献：
  名称：

  Syntheses and thymidylate synthase inhibitory activity of the poly-.gamma.-glutamyl conjugates of N-[5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino]-2-thenoyl]-L-glutamic acid (ICI D1694) and other quinazoline antifolates

  摘要：

  Thirteen poly-gamma-glutamates derived from several novel antifolates have been synthesized by a convergent route. The syntheses of poly-gamma-glutamyl conjugates of N-[5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino]-2-thenoyl]-L-glutamic acid (8) (ICI D1694), 2-desamino-N10-propargyl-5,8-dideazafolic acid (6), 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (7), 2-desamino-2-methyl-N10-propargyl-2'-fluoro-5,8-dideazafolic acid (9), and 2-desamino-2-methyl-4-chloro-N10-propargyl-2'-fluoro-3,5,8-trideazafolic acid (11) are described. A key step in the route involves coupling of an alpha-tert-butyl-protected poly-gamma-glutamate of the required chain length to the appropriate 5,8-dideazapteroic acid, obtained by carboxypeptidase G2 cleavage of the parent monoglutamate, if available, or by chemical synthesis. Deprotection with trifluoroacetic acid in the final step gave the desired poly-gamma-glutamyl antifolates as their trifluoroacetate salts. As inhibitors of thymidylate synthase, these polyglutamates were more potent in every case than the corresponding non-polyglutamylated drug.

  DOI：

  10.1021/jm00083a008

文献信息

• [EN] METHOTREXATE ANALOGS AND METHODS OF USE<br/>[FR] ANALOGUES DE MÉTHOTREXATE ET PROCÉDÉS D'UTILISATION
  申请人：US HEALTH

  公开号：WO2021262693A1

  公开（公告）日：2021-12-30

  Compounds having general formula (I) or a pharmaceutically acceptable salt, N-oxide, or hydrate thereof are provided herein. Also provided are methods of making the compounds and methods of their use, including in treatment of cancer, autoimmune disorders, and viral infections.

  本文提供了具有通式（I）或其药用可接受的盐、N-氧化物或水合物的化合物。还提供了制备这些化合物的方法以及它们的使用方法，包括在癌症、自身免疫性疾病和病毒感染的治疗中的应用。
• 雷替曲塞的合成方法
  申请人：上海鼎雅药物化学科技有限公司

  公开号：CN105111197B

  公开（公告）日：2021-05-04

  本发明提供了两种制备式4化合物的方法，方案一以5‑溴噻吩‑2‑甲酸甲酯为原料，与6‑((甲氨基)甲基)‑3,4‑二氢‑2‑甲基‑4‑氧代‑6‑喹唑啉(化合物1)反应制得2‑[N‑(2‑甲基‑4‑氧喹唑啉‑6‑甲基)‑N‑甲基]‑氨基噻吩‑2‑甲酸甲酯，然后在碱的水溶液中水解，再与L‑谷氨酸二乙酯经缩合反应制得式4化合物；方案二以5‑溴噻吩‑2‑甲酸为原料与L‑谷氨酸二酯经缩合制得N‑(5‑溴噻吩‑2‑基)谷氨酸二乙酯，再与式1化合物反应制得式4化合物；本发明还提供了一种制备雷替曲塞的方法，式4化合物在碱的水溶液中水解，再经盐酸酸化制得雷替曲塞。本发明采用的合成路线反应步骤少，操作简便，对环境污染小，产品收率高。
• ANTI-INFLAMMATORY PHOSPHONATE COMPOUNDS
  申请人：Cannizzaro Carina

  公开号：US20090247488A1

  公开（公告）日：2009-10-01

  The invention is related to phosphorus substituted anti-inflammatory compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

  本发明涉及磷取代的抗炎化合物、含有这种化合物的组合物、包括给药这种化合物的治疗方法，以及用于制备这种化合物的有用过程和中间体。
• ANTI-CANCER PHOSPHONATE ANALOGS
  申请人：Boojamra Constantine G.

  公开号：US20100022467A1

  公开（公告）日：2010-01-28

  The invention is related to phosphorus substituted anti-cancer compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

  本发明涉及磷取代的抗癌化合物、含有这些化合物的组合物以及包括给予这些化合物的治疗方法，还涉及用于制备这些化合物的过程和中间体。
• Nucleic acids encoding mutant human carboxypeptidase A enzymes
  申请人：Glaxo Wellcome, Inc.

  公开号：US06319702B1

  公开（公告）日：2001-11-20

  The present invention relates to nucleic acid molecules encoding mutant human carboxypeptidase A enzymes, and encoding conjugates of targeting molecules and mutant human carboxypeptidase A enzymes. The invention further relates to vectors and cell lines containing such nucleic acid molecules.

  本发明涉及编码突变人类羧肽酶A酶的核酸分子，以及编码靶向分子和突变人类羧肽酶A酶的共轭体的核酸分子。本发明还涉及包含这种核酸分子的载体和细胞系。