N-<2-bromo-4-(dimethylamino)phenyl>-4-chloro-6-methyltriazin-2-amine | 224195-03-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-<2-bromo-4-(dimethylamino)phenyl>-4-chloro-6-methyltriazin-2-amine
• 英文别名: 2-bromo-1-N-(4-chloro-6-methyl-1,3,5-triazin-2-yl)-4-N,4-N-dimethylbenzene-1,4-diamine
• CAS: 224195-03-3
• 化学式: C₁₂H₁₃BrClN₅
• 分子量: 342.626
• InChiKey: KJRVTSFIGQCVBY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  53.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-<2-bromo-4-(dimethylamino)phenyl>-4-chloro-6-methyltriazin-2-amine 在 sodium hydride 、 N,N-二异丙基乙胺 作用下， 反应 60.0h， 生成 4-N-[2-bromo-4-(dimethylamino)phenyl]-4-N-ethyl-6-methyl-2-N,2-N-bis(prop-2-enyl)-1,3,5-triazine-2,4-diamine
  参考文献：
  名称：

  Non-Peptide Corticotropin-Releasing Hormone Antagonists:  Syntheses and Structure−Activity Relationships of 2-Anilinopyrimidines and -triazines

  摘要：

  Screening of our chemical library using a rat corticotropin-releasing hormone (CRH) receptor assay led to the discovery that 2-anilinopyrimidine 15-1 weakly displaced [I-125]-0-Tyr-oCRH from rat frontal cortex homogenates when compared to the known peptide antagonist alpha-helical CRH(9-41) (K-i = 5700 nM vs 1 nM). Furthermore, 15-1 weakly inhibited CRH-stimulated adenylate cyclase activity in the same tissue, but it was less potent than a-helical CRH(9-41) (IC50 = 20 000 nM vs 250 nM). Systematic structure-activity relationship studies, using the cloned human CRH1 receptor assay, defined the pharmacophore for optimal binding to hCRH(1) receptors. Several high-affinity 2-anilinopyrimidines and -triazines were discovered, some of which had superior pharmacokinetic profiles in the rat. This paper describes the structure-activity studies which improved hCRH(1) receptor binding affinity and pharmacokinetic parameters in the rat. Compound 28-17 (mean hCRH(1) K-i = 32 nM) had a significantly improved pharmacokinetic profile in the rat (19% oral bioavailability at 30 mg/kg) as well as in the dog (20% oral bioavailability at 5 mg/kg) relative to the early lead structures.

  DOI：

  10.1021/jm980222w
• 作为产物：
  描述：

  2,4-二氯-6-甲基-1,3,5-三嗪 、 3-bromo-N1,N1-dimethylbenzene-1,4-diamine 在 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 16.0h， 以57%的产率得到N-<2-bromo-4-(dimethylamino)phenyl>-4-chloro-6-methyltriazin-2-amine
  参考文献：
  名称：

  Non-Peptide Corticotropin-Releasing Hormone Antagonists:  Syntheses and Structure−Activity Relationships of 2-Anilinopyrimidines and -triazines

  摘要：

  Screening of our chemical library using a rat corticotropin-releasing hormone (CRH) receptor assay led to the discovery that 2-anilinopyrimidine 15-1 weakly displaced [I-125]-0-Tyr-oCRH from rat frontal cortex homogenates when compared to the known peptide antagonist alpha-helical CRH(9-41) (K-i = 5700 nM vs 1 nM). Furthermore, 15-1 weakly inhibited CRH-stimulated adenylate cyclase activity in the same tissue, but it was less potent than a-helical CRH(9-41) (IC50 = 20 000 nM vs 250 nM). Systematic structure-activity relationship studies, using the cloned human CRH1 receptor assay, defined the pharmacophore for optimal binding to hCRH(1) receptors. Several high-affinity 2-anilinopyrimidines and -triazines were discovered, some of which had superior pharmacokinetic profiles in the rat. This paper describes the structure-activity studies which improved hCRH(1) receptor binding affinity and pharmacokinetic parameters in the rat. Compound 28-17 (mean hCRH(1) K-i = 32 nM) had a significantly improved pharmacokinetic profile in the rat (19% oral bioavailability at 30 mg/kg) as well as in the dog (20% oral bioavailability at 5 mg/kg) relative to the early lead structures.

  DOI：

  10.1021/jm980222w