2,4-diamino-5,6,7,8-tetrahydro-6-(L-erythro-1,2-dihydroxypropyl)-pteridine

• 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: 2,4-diamino-5,6,7,8-tetrahydro-6-(L-erythro-1,2-dihydroxypropyl)-pteridine
• 英文别名: H4-Aminobiopterin；1-(2,4-diamino-5,6,7,8-tetrahydropteridin-6-yl)propane-1,2-diol
• 化学式: C₉H₁₆N₆O₂
• 分子量: 240.265
• InChiKey: NDSDGUULXHNXGA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  17
• 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：
  142
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2,4-diamino-6-(1,2-dihydroxypropyl)pteridine 在 platinum(IV) oxide 氢气 作用下， 以 甲醇 为溶剂， 反应 48.0h， 生成 2,4-diamino-5,6,7,8-tetrahydro-6-(L-erythro-1,2-dihydroxypropyl)-pteridine
  参考文献：
  名称：

  Inhibition of Neuronal Nitric Oxide Synthase by 4-Amino Pteridine Derivatives:  Structure−Activity Relationship of Antagonists of (6R)-5,6,7,8-Tetrahydrobiopterin Cofactor

  摘要：

  The family of nitric oxide synthases (NOS) catalyzes the conversion of L-arginine to L-citrulline and nitric oxide (NO), an important cellular messenger molecule which has been implicated in the pathophysiology of septic shock and inflammatory and neurodegenerative disease states. NOS can be maximally activated by the ubiquitous cofactor, (6R)-5,6,7,8-tetrahydrobiopterin (H(4)Bip), and antagonists of H(4)Bip may be of therapeutic importance to inhibit pathologically high NO formation. The 4-amino substituted analogue of H(4)Bip was reported to be a potent NOS inhibit-or. Therefore, we developed a series of novel 4-amino pteridine derivatives, antipterins, to pharmacologically target the neuronal isoform of nitric oxide synthase (NOS-I). To functionally characterize the pterin/anti-pterin interaction and establish a structure-activity relationship (SAR), we systematically altered the substituents in the 2-, 4-, 5-, 6-, and 7-position of the pteridine nucleus. Varying the substitution pattern in the 2-, 5-, and 7-position resulted in no significant inhibitory effect on enzyme activity. In contrast, bulky substituents in the B-position, such as phenyl, markedly increased the inhibitory potency of the reduced 4-amino-5,6,7,8-tetrahydropteridines, possibly as a consequence of hydrophobic interactions within NOS-I. However, this was not the case for the aromatic 4-amino pteridines. Interestingly, chemical modification of the 4-amino substituent by dialkyl/diaralkylation together with 6-arylation of the aromatic 2,4-diamino pteridine resulted in potent and efficacious inhibitors of NOS-I, suggesting possible hydrophilic and hydrophobic interactions within NOS-I. This SAR agrees with (a) the recently published crystal structure of the oxygenase domain of the inducible NOS isoform (NOS-II) and (b) the comparative molecular field analysis of selected NOS-I inhibitors, which resulted in a 3D-QSAR model of the pterin binding site interactions. Further optimization should be possible when the full length structure of NOS-I becomes available.

  DOI：

  10.1021/jm981129a

文献信息

• USE OF PTERIDINE DERIVATIVES FOR THE TREATMENT OF INCREASED INTRACRANIAL PRESSURE, SECONDARY ISCHEMIA, AND DISORDERS ASSOCIATED WITH AN INCREASED LEVEL OF CYTOTOXIC REACTIVE OXYGEN SPECIES
  申请人：VASOPHARM GMBH

  公开号：US20130131071A1

  公开（公告）日：2013-05-23

  The present invention relates to the use of pteridine derivatives for the treatment of increased intracranial pressure, secondary ischemia, and disorders associated with an increased level of cytotoxic reactive oxygen species.

  本发明涉及使用黄嘌呤衍生物治疗颅内压增高、继发性缺血以及与细胞毒性活性氧自由基水平升高相关的疾病。
• Pteridinderivate als NO Synthase-Hemmer
  申请人：Werner, Ernst

  公开号：EP0906913A1

  公开（公告）日：1999-04-07

  Pteridinderivat der Formel wobei R1, R2, R3, R4 unabhängig voneinander für H oder OH stehen, R5 für H, CH3, CH2OH oder einen niederen Alkylrest (C1 bis C9) steht, der geradkettig oder verzweigt sein kann, sowie für (CH(OH))n-Y oder (CH(OH))n-(CH2)m-W, wobei Y Wasserstoff oder ein niederer Alkylrest, W ein Wasserstoff oder eine Hydroxylgruppe ist, und n und m unabhängig voneinander 1-20 sind, sowie tautomere und stereoisomere Formen von (I) und deren Salze.

  式中的蝶啶衍生物 其中 R1、R2、R3、R4 相互独立地代表 H 或 OH，R5 代表 H、CH3、CH2OH 或可为直链或支链的低级烷基（C1 至 C9），以及 (CH(OH))n-Y 或 (CH(OH))n-(CH2)m-W 、其中 Y 为氢或低级烷基，W 为氢或羟基，n 和 m 独立地为 1-20，以及 (I) 的同分异构体和立体异构体形式及其盐。
• Solid pharmaceutical compositions comprising biopterin derivatives and uses of suchcompositions
  申请人：VASOPHARM GMBH

  公开号：US10016431B2

  公开（公告）日：2018-07-10

  The present invention relates to a method of treating a disease in a subject, comprising administering to a subject in need thereof a solid pharmaceutical composition biopterin derivatives.

  本发明涉及一种治疗受试者疾病的方法，包括向有需要的受试者施用固体药物组合物生物蝶呤衍生物。
• Solid pharmaceutical compositions comprising biopterin derivatives and uses of such compositions
  申请人：VASOPHARM GMBH

  公开号：US10925877B2

  公开（公告）日：2021-02-23

  Compositions comprising derivatives of biopterin, useful for the treatment of traumatic brain injury, non-traumatic brain injury, elevated cranial pressure, and secondary brain injury.

  由生物蝶呤衍生物组成的复合物，可用于治疗创伤性脑损伤、非创伤性脑损伤、颅压升高和继发性脑损伤。
• Herstellung eines die Transplantatabstossung unterdrückenden Mittels
  申请人：Werner, Ernst

  公开号：EP0978283B1

  公开（公告）日：2002-10-16