5-(1,5-diphenyl-1H-pyrazol-3-yl)-4H-1,2,4-triazole-3-thiole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(1,5-diphenyl-1H-pyrazol-3-yl)-4H-1,2,4-triazole-3-thiole
• 英文别名: 3-(1,5-diphenyl-1H-pyrazol-3-yl)-4H-1,2,4-triazole-5-thiol；5-(1,5-Diphenylpyrazol-3-yl)-1,2-dihydro-1,2,4-triazole-3-thione
• 化学式: C₁₇H₁₃N₅S
• 分子量: 319.39
• InChiKey: TZGFLWJLRCGGBH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  86.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(1,5-diphenyl-1H-pyrazol-3-yl)-4H-1,2,4-triazole-3-thiole 在 过氧乙酸 作用下， 生成 3-(1,5-diphenylpyrazol-3-yl)-5-methylsulfonyl-1H-1,2,4-triazole
  参考文献：
  名称：

  1,2,4-Triazolsulfone: A novel isosteric replacement of acylsulfonamides in the context of Na V 1.7 inhibition

  摘要：

  Recently, the identification of several classes of aryl sulfonamides and acyl sulfonamides that potently inhibit Na(v)1.7 and demonstrate high levels of selectivity over other Na-v isoforms have been reported. The fully ionizable nature of these inhibitors has been shown to be an important part of the pharmacophore for the observed potency and isoform selectivity. The requirement of this functionality, however, has presented challenges associated with optimization toward inhibitors with drug-like properties and minimal off-target activity. In an effort to obviate these challenges, we set out to develop an orally bioavailable, selective Na(v)1.7 inhibitor, lacking these acidic functional groups. Herein, we report the discovery of a novel series of inhibitors wherein a triazolesulfone has been designed to serve as a bioisostere for the acyl sulfonamide. This work culminated in the delivery of a potent series of inhibitors which demonstrated good levels of selectivity over Na v 1.5 and favorable pharmacokinetics in rodents. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2018.04.035
• 作为产物：
  描述：

  3-苯丙烯溴酸酯 在 盐酸 、 sodium hydroxide 、 硫酸 、 乙酸酐 、 一水合肼 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 3.17h， 生成 5-(1,5-diphenyl-1H-pyrazol-3-yl)-4H-1,2,4-triazole-3-thiole
  参考文献：
  名称：

  方便地合成一些新的取代的吡唑基-1,3,4-恶二唑和吡唑基1,2,4-三唑

  摘要：

  一种简单而通用的合成吡唑-3-基-1,3,4-恶二唑，吡唑-3-基-1,2,4-三唑，（1,5-二苯基吡唑-3-基）-（ 1,5-二苯基吡唑-3-羧酸的3,5-二甲基-1-羰基）吡唑和（1,5-二苯基吡唑-3-基）-（5-羟基-3-甲基-1-基-1-羰基）吡唑衍生物酰肼已开发出来。

  DOI：

  10.1002/jhet.5570430508

文献信息

• Studies With Pyrazol-3-Carboxylic Acid Hydrazide: The Synthesis of New Pyrazolyloxadiazole and Pyrazolyltriazole Derivatives
  作者：Yehya M. Elkholy、Korany A. Ali、Ahmad M. Farag

  DOI：10.1080/10426500600605731

  日期：2006.9.1

  A simple and versatile method for the synthesis of pyrazol-3-yl-1,3,4-oxadiazole, pyrazol-3-yl-1,2,4-triazole, (1,5-diphenylpyrazol-3-yl)-(3,5-dimethyl-1-carbonyl)pyrazole, and (1,5-diphenylpyrazol-3-yl)-(5-hydroxy-3-metheyl-1-carbonyl)pyrazole derivatives from 1,5-diphenylpyrazole-3-carboxylic acid hydrazide has been developed.
• Convenient synthesis of some new substituted pyrazolyl-1,3,4-oxadiazoles and pyrazolyl-1,2,4-triazoles
  作者：Yehya M. Elkholy、Korany A. Ali、Ahmad M. Farag

  DOI：10.1002/jhet.5570430508

  日期：2006.9

  A simple and versatile method for the synthesis of pyrazol-3-yl-1,3,4-oxadiazole, pyrazol-3-yl-1,2,4-triazole, (1,5-diphenylpyrazol-3-yl)-(3,5-dimethyl-1-carbonyl)pyrazole and (1,5-diphenylpyrazol-3-yl)-(5-hydroxy-3-metheyl-1-carbonyl)pyrazole derivatives from 1,5-diphenylpyrazole-3-carboxylic acid hydrazide has been developed.

  一种简单而通用的合成吡唑-3-基-1,3,4-恶二唑，吡唑-3-基-1,2,4-三唑，（1,5-二苯基吡唑-3-基）-（ 1,5-二苯基吡唑-3-羧酸的3,5-二甲基-1-羰基）吡唑和（1,5-二苯基吡唑-3-基）-（5-羟基-3-甲基-1-基-1-羰基）吡唑衍生物酰肼已开发出来。
• 1,2,4-Triazolsulfone: A novel isosteric replacement of acylsulfonamides in the context of Na V 1.7 inhibition
  作者：Alessandro A. Boezio、Kristin Andrews、Christiane Boezio、Margaret Chu-Moyer、Katrina W. Copeland、Erin F. DiMauro、Robert S. Foti、Robert T. Fremeau、Hua Gao、Stephanie Geuns-Meyer、Russell F. Graceffa、Hakan Gunaydin、Hongbing Huang、Daniel S. La、Joseph Ligutti、Bryan D. Moyer、Emily A. Peterson、Violeta Yu、Matthew M. Weiss

  DOI：10.1016/j.bmcl.2018.04.035

  日期：2018.6

  Recently, the identification of several classes of aryl sulfonamides and acyl sulfonamides that potently inhibit Na(v)1.7 and demonstrate high levels of selectivity over other Na-v isoforms have been reported. The fully ionizable nature of these inhibitors has been shown to be an important part of the pharmacophore for the observed potency and isoform selectivity. The requirement of this functionality, however, has presented challenges associated with optimization toward inhibitors with drug-like properties and minimal off-target activity. In an effort to obviate these challenges, we set out to develop an orally bioavailable, selective Na(v)1.7 inhibitor, lacking these acidic functional groups. Herein, we report the discovery of a novel series of inhibitors wherein a triazolesulfone has been designed to serve as a bioisostere for the acyl sulfonamide. This work culminated in the delivery of a potent series of inhibitors which demonstrated good levels of selectivity over Na v 1.5 and favorable pharmacokinetics in rodents. (C) 2018 Elsevier Ltd. All rights reserved.