5-(4-biphenyl)-4-(2-hydroxy-6-methylphenyl)-3-methyl-1,2,4-triazole | 258878-32-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-(4-biphenyl)-4-(2-hydroxy-6-methylphenyl)-3-methyl-1,2,4-triazole
• 英文别名: 3-Methyl-2-[3-methyl-5-(4-phenylphenyl)-1,2,4-triazol-4-yl]phenol
• CAS: 258878-32-9
• 化学式: C₂₂H₁₉N₃O
• 分子量: 341.412
• InChiKey: SKLRMVJBPBCDSC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  50.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(4-biphenyl)-4-(2-hydroxy-6-methylphenyl)-3-methyl-1,2,4-triazole 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 生成 1-{6-[2-(3-Biphenyl-4-yl-5-methyl-[1,2,4]triazol-4-yl)-3-methyl-phenoxy]-hexyl}-4-methyl-piperazine
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of 5-(4-Biphenyl)-3-methyl-4-phenyl-1,2,4-triazole Derivatives as a Novel Class of Selective Antagonists for the Human Vasopressin V_1A Receptor

  摘要：

  A series of 5-(4-biphenyl)-3-methyl-4-phenyl-1,2,4-triazole derivatives were prepared and evaluated as selective antagonists for the human vasopressin VIA receptor. The compounds were examined for their affinity to the cloned human VIA receptor (hV(1A)) and selectivity vs the cloned human V-2 receptor (hV(2)). By utilizing the structure-activity relationship on 4,4-difluoro-5-methylidene-2,3,4,5-tetrahydrobenzazepine derivatives as dual antagonists for the VIA and V2 receptors in our previous study, we found that substituting the methoxy group at the 2-position of the 4-phenyl ring with (4-methylpiperazin-1-yl)alkoxy moieties brought about marked improvement of both affinity to hV1A and selectivity vs hV2. Further introduction of a methyl group into the 6-position of the 4-phenyl ring resulted in additional improvement of selectivity. One particular compound, 5-(4-biphenyl)-3-methyl-4-{2-[6-(4-methyl-1-piperazinyl)-hexyloxy]phenyl}-1,2,4-triazole (19) showed potent affinity to hV(1A) with a K-i value of 1.04 nM and high selectivity with a 1700-fold selectivity vs hV(2). We also found marked differences in the affinity of compounds in this series between the human and the rat receptors. Compound 19 was further examined for its VIA receptor antagonist activity in rats. As a result, 19 demonstrated antagonist activities toward an arginine vasopressin-induced increase in diastolic blood pressure after intravenous or oral administration and long-lasting oral activity.

  DOI：

  10.1021/jm010544r
• 作为产物：
  描述：

  2-氨基-3-甲基苯酚 在 10percent Pd/C 氢气 、 potassium carbonate 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 20.0~120.0 ℃ 、405.33 kPa 条件下， 生成 5-(4-biphenyl)-4-(2-hydroxy-6-methylphenyl)-3-methyl-1,2,4-triazole
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of 5-(4-Biphenyl)-3-methyl-4-phenyl-1,2,4-triazole Derivatives as a Novel Class of Selective Antagonists for the Human Vasopressin V_1A Receptor

  摘要：

  A series of 5-(4-biphenyl)-3-methyl-4-phenyl-1,2,4-triazole derivatives were prepared and evaluated as selective antagonists for the human vasopressin VIA receptor. The compounds were examined for their affinity to the cloned human VIA receptor (hV(1A)) and selectivity vs the cloned human V-2 receptor (hV(2)). By utilizing the structure-activity relationship on 4,4-difluoro-5-methylidene-2,3,4,5-tetrahydrobenzazepine derivatives as dual antagonists for the VIA and V2 receptors in our previous study, we found that substituting the methoxy group at the 2-position of the 4-phenyl ring with (4-methylpiperazin-1-yl)alkoxy moieties brought about marked improvement of both affinity to hV1A and selectivity vs hV2. Further introduction of a methyl group into the 6-position of the 4-phenyl ring resulted in additional improvement of selectivity. One particular compound, 5-(4-biphenyl)-3-methyl-4-{2-[6-(4-methyl-1-piperazinyl)-hexyloxy]phenyl}-1,2,4-triazole (19) showed potent affinity to hV(1A) with a K-i value of 1.04 nM and high selectivity with a 1700-fold selectivity vs hV(2). We also found marked differences in the affinity of compounds in this series between the human and the rat receptors. Compound 19 was further examined for its VIA receptor antagonist activity in rats. As a result, 19 demonstrated antagonist activities toward an arginine vasopressin-induced increase in diastolic blood pressure after intravenous or oral administration and long-lasting oral activity.

  DOI：

  10.1021/jm010544r

文献信息

• [EN] LABELED LIGANDS OF THE OXYTOCIN RECEPTOR<br/>[FR] LIGANDS MARQUÉS DU RÉCEPTEUR DE L'OCYTOCINE
  申请人：UNIV STRASBOURG

  公开号：WO2014056852A1

  公开（公告）日：2014-04-17

  The invention relates to compounds of formula (I) wherein L and A are as defined in the description. These compounds can be used as ligands of the oxytocin receptor.

  这项发明涉及公式（I）中的化合物，其中L和A如描述中所定义。这些化合物可以用作催产素受体的配体。
• Synthesis and Pharmacological Evaluation of 5-(4-Biphenyl)-3-methyl-4-phenyl-1,2,4-triazole Derivatives as a Novel Class of Selective Antagonists for the Human Vasopressin V_1A Receptor
  作者：Akio Kakefuda、Takeshi Suzuki、Takahiko Tobe、Junko Tsukada、Atsuo Tahara、Shuichi Sakamoto、Shin-ichi Tsukamoto

  DOI：10.1021/jm010544r

  日期：2002.6.1

  A series of 5-(4-biphenyl)-3-methyl-4-phenyl-1,2,4-triazole derivatives were prepared and evaluated as selective antagonists for the human vasopressin VIA receptor. The compounds were examined for their affinity to the cloned human VIA receptor (hV(1A)) and selectivity vs the cloned human V-2 receptor (hV(2)). By utilizing the structure-activity relationship on 4,4-difluoro-5-methylidene-2,3,4,5-tetrahydrobenzazepine derivatives as dual antagonists for the VIA and V2 receptors in our previous study, we found that substituting the methoxy group at the 2-position of the 4-phenyl ring with (4-methylpiperazin-1-yl)alkoxy moieties brought about marked improvement of both affinity to hV1A and selectivity vs hV2. Further introduction of a methyl group into the 6-position of the 4-phenyl ring resulted in additional improvement of selectivity. One particular compound, 5-(4-biphenyl)-3-methyl-4-2-[6-(4-methyl-1-piperazinyl)-hexyloxy]phenyl}-1,2,4-triazole (19) showed potent affinity to hV(1A) with a K-i value of 1.04 nM and high selectivity with a 1700-fold selectivity vs hV(2). We also found marked differences in the affinity of compounds in this series between the human and the rat receptors. Compound 19 was further examined for its VIA receptor antagonist activity in rats. As a result, 19 demonstrated antagonist activities toward an arginine vasopressin-induced increase in diastolic blood pressure after intravenous or oral administration and long-lasting oral activity.