4-methyl-3-phenyl-5-(propylthio)-4H-1,2,4-triazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-methyl-3-phenyl-5-(propylthio)-4H-1,2,4-triazole
• 英文别名: 4-Methyl-3-phenyl-5-propylsulfanyl-1,2,4-triazole
• 化学式: C₁₂H₁₅N₃S
• mdl: MFCD09870139
• 分子量: 233.337
• InChiKey: CBFQPELWTJSDFA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  56
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  正溴丁烷 、 5-苯基-4-甲基-4氢-3-羟基-1,2,4-三唑 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 12.0h， 以81%的产率得到4-methyl-3-phenyl-5-(propylthio)-4H-1,2,4-triazole
  参考文献：
  名称：

  [EN] SELECTIVE DOPAMINE RECEPTOR ANTAGONISTS AND METHODS OF THEIR USE
  [FR] ANTAGONISTES SÉLECTIFS DU RÉCEPTEUR DE LA DOPAMINE ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  该披露涉及螺环式、选择性多巴胺受体拮抗剂及其在治疗多巴胺D3受体介导的疾病和紊乱方面的使用方法。

  公开号：

  WO2019084075A1

文献信息

• Leveraging a Low-Affinity Diazaspiro Orthosteric Fragment to Reduce Dopamine D₃ Receptor (D₃R) Ligand Promiscuity across Highly Conserved Aminergic G-Protein-Coupled Receptors (GPCRs)
  作者：Sean W. Reilly、Aladdin A. Riad、Chia-Ju Hsieh、Kristoffer Sahlholm、Daniel A. Jacome、Suzy Griffin、Michelle Taylor、Chi-Chang Weng、Kuiying Xu、Nathan Kirschner、Robert R. Luedtke、Christopher Parry、Shipra Malhotra、John Karanicolas、Robert H. Mach

  DOI：10.1021/acs.jmedchem.9b00412

  日期：2019.5.23

  Previously, we reported a 3-(2-methoxyphenyl)-9-(3-((4-methyl-5-phenyl-4H-1,2,4-triazol-3-yl)thio)-propyl)-3,9-diazaspiro[5.5]undecane (1) compound with excellent dopamine D-3 receptor (D3R) affinity (D3R K-i = 12.0 nM) and selectivity (D2R/D3R ratio = 905). Herein, we present derivatives of 1 with comparable D3R affinity (32, D3R K-i = 3.2 nM, D2R/D3R ratio = 60) and selectivity (30, D3R K-i = 21.0 nM, D2R/D3R ratio = 934). Fragmentation of 1 revealed orthosteric fragment 5a to express an unusually low D3R affinity (K-i = 2.7 mu M). Compared to piperazine congener 31, which retains a high-affinity orthosteric fragment (5d, D3R K-i = 23.9 nM), 1 was found to be more selective for the D3R among D-1- and D-2-like receptors and exhibited negligible off-target interactions at serotoninergic and adrenergic G-protein-coupled receptors (GPCRs), common off-target sites for piperazine-containing D3R scaffolds. This study provides a unique rationale for implementing weakly potent orthosteric fragments into D3R ligand systems to minimize drug promiscuity at other aminergic GPCR sites.