2,4-diamino-6-(p-methoxyphenyl)pteridine | 192587-18-1

• 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-6-(p-methoxyphenyl)pteridine
• 英文别名: 6-(4-Methoxyphenyl)pteridine-2,4-diamine
• CAS: 192587-18-1
• 化学式: C₁₃H₁₂N₆O
• 分子量: 268.278
• InChiKey: VKTKNSWSDBQLPB-UHFFFAOYSA-N

物化性质

• 熔点：
  >300 °C
• 沸点：
  581.0±60.0 °C(Predicted)
• 密度：
  1.409±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2,4-diamino-7-(p-methoxyphenyl)pteridine 、 2,4-diamino-6-(p-methoxyphenyl)pteridine 在 sodium hydroxide 、 水 作用下， 生成 2-amino-7-(p-methoxyphenyl)pterin 、 2-amino-6-(p-methoxyphenyl)pterin
  参考文献：
  名称：

  Immunosuppressive effects of pteridine derivatives

  摘要：

  这项发明涉及一组三取代和四取代的嘌呤衍生物，它们的药用盐、N-氧化物、溶剂化物、二氢和四氢衍生物及对映异构体，具有意想不到的、令人满意的药理性质，尤其是作为高度活性的免疫抑制剂，因此可用于治疗移植排斥反应和/或治疗某些炎症性疾病。这些化合物还用于预防或治疗心血管疾病、过敏性疾病、中枢神经系统疾病和细胞增殖紊乱。

  公开号：

  US20040077859A1
• 作为产物：
  描述：

  (4-甲氧基苯基)-氧代-乙醛肟 、 2,4,5,6-四氨基嘧啶盐酸盐 以 甲醇 为溶剂， 反应 2.0h， 以91%的产率得到2,4-diamino-6-(p-methoxyphenyl)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

• Pteridine derivatives for the treatment of septic shock and tnf-a-related diseases
  申请人：Waer Mark Jozef Albert

  公开号：US20070004721A1

  公开（公告）日：2007-01-04

  This invention relates to the use of a group of pteridine derivatives, their pharmaceutically acceptable salts, N-oxides, solvates, dihydro- and tetrahydroderivatives and enantiomers, for the manufacture of a medicament for the prevention or treatment of TNF-α related disorders.

  该发明涉及使用一组黄素衍生物及其医药上可接受的盐、N-氧化物、溶剂合物、二氢-和四氢衍生物和对映体，制造用于预防或治疗与TNF-α相关的疾病的药物。
• IMMUNOSUPPRESSIVE EFFECTS OF PTERIDINE DERIVATIVES
  申请人：4 AZA Bioscience nv

  公开号：EP1658081A2

  公开（公告）日：2006-05-24
• PTERIDINE DERIVATIVES FOR THE TREATMENT OF TNF-ALPHA-RELATED DISEASES.
  申请人：4 AZA IP NV

  公开号：EP1663244B1

  公开（公告）日：2007-08-15
• US7276506B2
  申请人：——

  公开号：US7276506B2

  公开（公告）日：2007-10-02
• US7501513B2
  申请人：——

  公开号：US7501513B2

  公开（公告）日：2009-03-10