5-(Dimethylamino)-2-[(4,6-dimethylpyrimidin-2-yl)amino]benzenethiol | 1027894-07-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯硫酚类
• 英文名称: 5-(Dimethylamino)-2-[(4,6-dimethylpyrimidin-2-yl)amino]benzenethiol
• CAS: 1027894-07-0
• 化学式: C₁₄H₁₈N₄S
• 分子量: 274.39
• InChiKey: KYPDPYJINZYFLR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  42
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(Dimethylamino)-2-[(4,6-dimethylpyrimidin-2-yl)amino]benzenethiol 在 sodium tetrahydroborate 、 乙醇 、 sodium hydride 作用下， 生成 N-(4-(N,N-dimethylamino)-2-methylthiophenyl)-N-ethyl-4,6-dimethyl-2-pyrimidinamine
  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：

  4,6-二甲基-2-巯基嘧啶 在 盐酸 、 铜 、 potassium carbonate 作用下， 以 甲醇 、 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 60.0h， 生成 5-(Dimethylamino)-2-[(4,6-dimethylpyrimidin-2-yl)amino]benzenethiol
  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