4-(4-methylsulfonylphenyl)-1H-pyrazol-5-amine

• 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-(4-methylsulfonylphenyl)-1H-pyrazol-5-amine
• 化学式: C₁₀H₁₁N₃O₂S
• 分子量: 237.282
• InChiKey: YNOMSZGZUVGNDW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  97.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(4-methylsulfonylphenyl)-1H-pyrazol-5-amine 、 在 盐酸 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 生成 Methyl 3-benzyl-10-(4-methylsulfonylphenyl)-1,8,12-triazatricyclo[7.3.0.02,6]dodeca-2(6),7,9,11-tetraene-3-carboxylate
  参考文献：
  名称：

  Novel tricyclic pyrazolopyrimidines as potent and selective GPR119 agonists

  摘要：

  Systematic SAR optimization of the GPR119 agonist lead 1, derived from an internal HTS campaign, led to compound 29. Compound 29 displays significantly improved in vitro activity and oral exposure, leading to GLP1 elevation in acutely dosed mice and reduced glucose excursion in an OGTT study in rats at doses >= 10 mg/kg. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.10.010
• 作为产物：
  描述：

  4-(甲基磺酰基)苯乙腈 在 盐酸 、 盐酸肼 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 96.5h， 生成 4-(4-methylsulfonylphenyl)-1H-pyrazol-5-amine
  参考文献：
  名称：

  Novel tricyclic pyrazolopyrimidines as potent and selective GPR119 agonists

  摘要：

  Systematic SAR optimization of the GPR119 agonist lead 1, derived from an internal HTS campaign, led to compound 29. Compound 29 displays significantly improved in vitro activity and oral exposure, leading to GLP1 elevation in acutely dosed mice and reduced glucose excursion in an OGTT study in rats at doses >= 10 mg/kg. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.10.010

文献信息

• Discovery of structurally novel, potent and orally efficacious GPR119 agonists
  作者：Phil Alper、Mihai Azimioara、Christopher Cow、Daniel Mutnick、Victor Nikulin、Pierre-Yves Michellys、Zhiliang Wang、Esther Reding、Michael Paliotti、Jing Li、Dingjiu Bao、Jocelyn Zoll、Young Kim、Matthew Zimmerman、Todd Groessel、Tove Tuntland、Sean B. Joseph、Peter McNamara、H. Martin Seidel、Robert Epple

  DOI：10.1016/j.bmcl.2014.03.023

  日期：2014.5

  Screening hit 5 was identified in a biochemical screen for GPR119 agonists. Compound 5 was structurally novel, displayed modest biochemical activity and no oral exposure, but was structurally distinct from typical GPR119 agonist scaffolds. Systematic optimization led to compound 36 with significantly improved in vitro activity and oral exposure, to elevate GLP1 acutely in an in vivo mouse model at a dose of 10 mg/kg. (C) 2014 Elsevier Ltd. All rights reserved.