6(R)-propyl-5,6,7,8-tetrahydropterin | 136778-65-9

• 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: 6(R)-propyl-5,6,7,8-tetrahydropterin
• 英文别名: (6R)-2-amino-6-propyl-5,6,7,8-tetrahydro-3H-pteridin-4-one
• CAS: 136778-65-9
• 化学式: C₉H₁₅N₅O
• 分子量: 209.251
• InChiKey: NABLTMGJMSJTNW-RXMQYKEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  91.5
• 氢给体数：
  4
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  6-<(2(R)-aminopentyl)amino>-2,5-diamino-4(3H)-pyrimidinone 生成 6(R)-propyl-5,6,7,8-tetrahydropterin
  参考文献：
  名称：

  Synthesis of tetrahydropteridine C6-stereoisomers, including N5-formyl-(6S)-tetrahydrofolic acid

  摘要：

  Chiral N1-protected vicinal diamines derived from amino acids were condensed with 2-amino-6-chloro-5-nitro-4(3H)-pyrimidinone, the nitro group reduced, and the amine deprotected. oxidative cyclization of the resulting triaminopyrimidinone via quinoid pyrimidine intermediates gave a quinoid dihydropteridine, which was then reduced to a tetrahydropteridine C6-stereoisomer. Thus, 6(R)- and 6(S)-propyltetrahydropterin were stereospecifically synthesized (99% enantiomeric purity) in good yield from D- and L-norvaline, respectively. Reductive alkylation of (p-aminobenzoyl)-L-glutamate with a nitropyrimidine aldehyde derived from D- or L-serine similarly afforded, after cyclization and reduction, (6R)- or (6S)-tetrahydrofolic acid. The latter was then converted to the natural isomer of leucovorin by regioselective N5-formylation with carbonyl diimidazole/formic acid without loss of enantiomeric purity.

  DOI：

  10.1021/jo00042a030

文献信息

• PREPARATION WITH IMPROVED BIOABSORBABILITY OF SAPROPTERIN HYDROCHLORIDE
  申请人：Asubio Pharma Co., Ltd.

  公开号：EP1964566A1

  公开（公告）日：2008-09-03

  A method of significant improvement for the bioavailability of orally administered sapropterin hydrochloride, a therapeutic agent used to treat BH4-responsive hyperphenylalaninemia, is provided. Also provided is a preparation for oral administration or ingestion having an improved bioavailability of sapropterin hydrochloride. Specifically, the preparation having an improved bioavailability of sapropterin hydrochloride contains sapropterin hydrochloride and an absorption promoter including an organic carboxylic acid having more than one carboxyl group in its molecule. The organic carboxylic acid having more than one carboxyl group in its molecule is selected from tartaric acid, citric acid, malic acid and optically active substances thereof, racemic mixtures thereof, anhydrides thereof, hydrates thereof or mixtures thereof. The amount by weight of the organic carboxylic acid is 0.1 to 100 times that of sapropterin hydrochloride.

  提供了一种显著提高口服盐酸沙泊泼尼汀生物利用度的方法，盐酸沙泊泼尼汀是一种用于治疗 BH4 反应性高苯丙氨酸血症的治疗剂。还提供了一种口服或摄入制剂，其盐酸沙泊泼尼汀的生物利用度有所提高。具体而言，该制剂具有更高的盐酸沙泊泼尼汀生物利用度，包含盐酸沙泊泼尼汀和吸收促进剂，吸收促进剂包括分子中含有一个以上羧基的有机羧酸。分子中含有一个以上羧基的有机羧酸选自酒石酸、柠檬酸、苹果酸及其光学活性物质、外消旋混合物、酸酐、水合物或其混合物。按重量计，有机羧酸的用量是盐酸沙泊三嗪的 0.1 至 100 倍。
• Synthesis of tetrahydropteridine C6-stereoisomers, including N5-formyl-(6S)-tetrahydrofolic acid
  作者：Steven W. Bailey、Rama Y. Chandrasekaran、June E. Ayling

  DOI：10.1021/jo00042a030

  日期：1992.7

  Chiral N1-protected vicinal diamines derived from amino acids were condensed with 2-amino-6-chloro-5-nitro-4(3H)-pyrimidinone, the nitro group reduced, and the amine deprotected. oxidative cyclization of the resulting triaminopyrimidinone via quinoid pyrimidine intermediates gave a quinoid dihydropteridine, which was then reduced to a tetrahydropteridine C6-stereoisomer. Thus, 6(R)- and 6(S)-propyltetrahydropterin were stereospecifically synthesized (99% enantiomeric purity) in good yield from D- and L-norvaline, respectively. Reductive alkylation of (p-aminobenzoyl)-L-glutamate with a nitropyrimidine aldehyde derived from D- or L-serine similarly afforded, after cyclization and reduction, (6R)- or (6S)-tetrahydrofolic acid. The latter was then converted to the natural isomer of leucovorin by regioselective N5-formylation with carbonyl diimidazole/formic acid without loss of enantiomeric purity.