2-[(6-氯-1,3-苯并噻唑-2-YL)硫代]苯胺 | 740787-10-4

• 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
• 中文名称: 2-[(6-氯-1,3-苯并噻唑-2-YL)硫代]苯胺
• 中文别名: 1,5,6,7-四氢-N2-甲基-2,4-蝶啶二胺
• 英文名称: N²-Methyl-5,6,7,8-tetrahydro-pteridine-2,4-diamine
• 英文别名: 2,4-Pteridinediamine,1,5,6,7-tetrahydro-N2-methyl-(9CI)；2-N-methyl-5,6,7,8-tetrahydropteridine-2,4-diamine
• CAS: 740787-10-4
• 化学式: C₇H₁₂N₆
• 分子量: 180.212
• InChiKey: MPJGSEOZOYGCFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  87.9
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-amino-2-methylaminopteridine 在 platinum(IV) oxide 氢气 作用下， 以 三氟乙酸 为溶剂， 生成 2-[(6-氯-1,3-苯并噻唑-2-YL)硫代]苯胺
  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