1-(4-ethynylphenyl)-4-methyl-1H-imidazole | 1093980-62-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(4-ethynylphenyl)-4-methyl-1H-imidazole
• 英文别名: 1-(4-ethynylphenyl)-4-methylimidazole
• CAS: 1093980-62-1
• 化学式: C₁₂H₁₀N₂
• 分子量: 182.225
• InChiKey: HQYNQKXIIQRBJQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-azido-N-(2,3-dichlorophenyl)acetamide 、 1-(4-ethynylphenyl)-4-methyl-1H-imidazole 在 copper(II) sulfate 、 sodium ascorbate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-(2,3-dichlorophenyl)-2-[4-[4-(4-methylimidazol-1-yl)phenyl]triazol-1-yl]acetamide
  参考文献：
  名称：

  Discovery and Optimization of a Novel Triazole Series of GPR142 Agonists for the Treatment of Type 2 Diabetes

  摘要：

  GPR142 has been identified as a potential glucose-stimulated insulin secretion (GSIS) target for the treatment of type 2 diabetes mellitus (T2DM). A class of triazole GPR142 agonists was discovered through a high throughput screen. The lead compound 4 suffered from poor metabolic stability and poor solubility. Lead optimization strategies to improve potency, efficacy, metabolic stability, and solubility are described. This optimization led to compound 20e, which showed significant reduction of glucose excursion in wild-type but not in GPR142 deficient mice in an oral glucose tolerance test (oGTT) study. These studies provide strong evidence that reduction of glucose excursion through treatment with 20e is GPR142-mediated, and GPR142 agonists could be used as a potential treatment for type 2 diabetes.

  DOI：

  10.1021/acsmedchemlett.6b00314
• 作为产物：
  描述：

  对氟苯甲醛 在 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 43.0h， 生成 1-(4-ethynylphenyl)-4-methyl-1H-imidazole
  参考文献：
  名称：

  Maximizing Diversity from a Kinase Screen: Identification of Novel and Selective pan-Trk Inhibitors for Chronic Pain

  摘要：

  We have identified several series of small molecule inhibitors of TrkA with unique binding modes. The starting leads were chosen to maximize the structural and binding mode diversity derived from a high throughput screen of our internal compound collection. These leads were optimized for potency and selectivity employing a structure based drug design approach adhering to the principles of ligand efficiency to maximize binding affinity without overly relying on lipophilic interactions. This endeavor resulted in the identification of several small molecule pan-Trk inhibitor series that exhibit high selectivity for TrkA/B/C versus a diverse panel of kinases. We have also demonstrated efficacy in both inflammatory and neuropathic pain models upon oral dosing. Herein we describe the identification process, hit-to-lead progression, and binding profiles of these selective pan-Trk kinase inhibitors.

  DOI：

  10.1021/jm5006429

文献信息

• TRIAZOLE DERIVATIVES FOR TREATING ALZHEIMER'S DISEASE AND RELATED CONDITIONS
  申请人：Fischer Christian

  公开号：US20100222320A1

  公开（公告）日：2010-09-02

  Compounds of formula I: Selectively attenuate production of Aβ(1-42) and hence find use in treatment or prevention of diseases associated with deposition of Aβ in the brain, in particular Alzheimer's disease.

  公式为I的化合物：选择性地减弱Aβ（1-42）的产生，因此可用于治疗或预防与Aβ在大脑中沉积相关的疾病，特别是阿尔茨海默病。
• Triazole derivatives for treating alzheimer'S disease and related conditions
  申请人：Merck Sharp & Dohme Corp.

  公开号：US08242150B2

  公开（公告）日：2012-08-14

  Compounds of formula I: Selectively attenuate production of Aβ(1-42) and hence find use in treatment or prevention of diseases associated with deposition of Aβ in the brain, in particular Alzheimer's disease.

  化合物I的公式：选择性地减弱Aβ（1-42）的产生，因此可用于治疗或预防与Aβ在大脑沉积有关的疾病，特别是阿尔茨海默病。
• Maximizing Diversity from a Kinase Screen: Identification of Novel and Selective pan-Trk Inhibitors for Chronic Pain
  作者：Shawn J. Stachel、John M. Sanders、Darrell A. Henze、Mike T. Rudd、Hua-Poo Su、Yiwei Li、Kausik K. Nanda、Melissa S. Egbertson、Peter J. Manley、Kristen L. G. Jones、Edward J. Brnardic、Ahren Green、Jay A. Grobler、Barbara Hanney、Michael Leitl、Ming-Tain Lai、Vandna Munshi、Dennis Murphy、Keith Rickert、Daniel Riley、Alicja Krasowska-Zoladek、Christopher Daley、Paul Zuck、Stephanie A. Kane、Mark T. Bilodeau

  DOI：10.1021/jm5006429

  日期：2014.7.10

  We have identified several series of small molecule inhibitors of TrkA with unique binding modes. The starting leads were chosen to maximize the structural and binding mode diversity derived from a high throughput screen of our internal compound collection. These leads were optimized for potency and selectivity employing a structure based drug design approach adhering to the principles of ligand efficiency to maximize binding affinity without overly relying on lipophilic interactions. This endeavor resulted in the identification of several small molecule pan-Trk inhibitor series that exhibit high selectivity for TrkA/B/C versus a diverse panel of kinases. We have also demonstrated efficacy in both inflammatory and neuropathic pain models upon oral dosing. Herein we describe the identification process, hit-to-lead progression, and binding profiles of these selective pan-Trk kinase inhibitors.
• WO2008/156580
  申请人：——

  公开号：——

  公开（公告）日：——
• US8242150B2
  申请人：——

  公开号：US8242150B2

  公开（公告）日：2012-08-14