2-amino-4-(dibenzylamino)-6-(3,4-dimethoxyphenyl)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-amino-4-(dibenzylamino)-6-(3,4-dimethoxyphenyl)pteridine
• 英文别名: N*4*,N*4*-Dibenzyl-6-(3,4-dimethoxy-phenyl)-pteridine-2,4-diamine；4-N,4-N-dibenzyl-6-(3,4-dimethoxyphenyl)pteridine-2,4-diamine
• 化学式: C₂₈H₂₆N₆O₂
• 分子量: 478.553
• InChiKey: CFIFWSGTEXYFLX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  99.3
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3,4-dimethoxyphenylglyoxalmonoxime 、 2,5,6-triamino-4-dibenzylaminopyrimidine dihydrochloride 以 甲醇 为溶剂， 反应 3.0h， 以65%的产率得到2-amino-4-(dibenzylamino)-6-(3,4-dimethoxyphenyl)pteridine
  参考文献：
  名称：

  Structural Requirements for Inhibition of the Neuronal Nitric Oxide Synthase (NOS-I):  3D-QSAR Analysis of 4-Oxo- and 4-Amino-Pteridine-Based Inhibitors

  摘要：

  The family of homodimeric nitric oxide synthases (NOS I-III) catalyzes the generation of the cellular messenger nitric oxide (NO) by oxidation of the substrate L-arginine. The rational design of specific NOS inhibitors is of therapeutic interest in regulating pathological NO levels associated with sepsis, inflammatory, and neurodegenerative diseases. The cofactor (6R)-5,6,7,8-tetrahydrobiopterin (H(4)Bip) maximally activates all NOSs and stabilizes enzyme quaternary structure by promoting and stabilizing dimerization. Here, we describe the synthesis and three-dimensional (3D) quantitative structure-activity relationship (QSAR) analysis of 65 novel 4-amino- and 4-oxo-pteridines (antipterins) as inhibitors targeting the H(4)Bip binding site of the neuronal NOS isoform (NOS-I). The experimental binding modes for two inhibitors complexed with the related endothelial NO synthase (NOS-III) reveal requirements of biological affinity and form the basis for ligand alignment. Different alignment rules were derived by building other compounds accordingly using manual superposition or a genetic algorithm for flexible superposition. Those alignments led to 3D-QSAR models (comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA)), which were validated using leave-one-out cross-validation, multiple analyses with two and five randomly chosen cross-validation groups, perturbation of biological activities by randomization or progressive scrambling, and external prediction. An iterative realignment procedure based on rigid field fit was used to improve the consistency of the resulting partial least squares models. This led to consistent and highly predictive 3D-QSAR models with good correlation coefficients for both CoMFA and CoMSIA, which correspond to experimentally determined NOS-II and -III H(4)Bip binding site topologies as well as to the NOS-I homology model binding site in terms of steric, electrostatic, and hydrophobic complementarity. These models provide clear guidelines and accurate activity predictions for novel NOS-I inhibitors.

  DOI：

  10.1021/jm020074g

文献信息

• Immunosuppressive effects of pteridine derivatives
  申请人：——

  公开号：US20040077859A1

  公开（公告）日：2004-04-22

  This invention relates to a group of trisubstituted and tetrasubstituted pteridine derivatives, their pharmaceutically acceptable salts, N-oxides, solvates, dihydro- and tetrahydroderivatives and enantiomers, possessing unexpectedly desirable pharmaceutical properties, in particular which are highly active immunosuppressive agents, and as such are useful in the treatment in transplant rejection and/or in the treatment of certain inflammatory diseases. These compounds are also useful in preventing or treating cardiovascular disorders, allergic conditions, disorders of the central nervous system and cell proliferative disorders.

  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。
• 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：EP1144412B1

  公开（公告）日：2004-09-29
• N-SUBSTITUIERTE 4-AMINOPTERIDINE, VERFAHREN ZU IHRER HERSTELLUNG UND IHRE VERWENDUNG ALS ARZNEIMITTEL
  申请人：Vasopharm Biotech GmbH & Co. KG

  公开号：EP1216246B1

  公开（公告）日：2005-08-24
• PTERIDINE DERIVATIVES FOR THE TREATMENT OF SEPTIC SHOCK AND TNF-ALPHA-RELATED DISEASES.
  申请人：4 AZA Bioscience nv

  公开号：EP1663244A2

  公开（公告）日：2006-06-07