3-chloro-2-methyl-N-(5-(1-methyl-1H-benzo[d]imidazol-2-yl)thiazol-2-yl)benzamide

• 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: 3-chloro-2-methyl-N-(5-(1-methyl-1H-benzo[d]imidazol-2-yl)thiazol-2-yl)benzamide
• 英文别名: 3-chloro-2-methyl-N-[5-(1-methylbenzimidazol-2-yl)-1,3-thiazol-2-yl]benzamide
• 化学式: C₁₉H₁₅ClN₄OS
• 分子量: 382.873
• InChiKey: XEPQGVMTJRGTCD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  88
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-甲基-1,2-苯二胺 在 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成 3-chloro-2-methyl-N-(5-(1-methyl-1H-benzo[d]imidazol-2-yl)thiazol-2-yl)benzamide
  参考文献：
  名称：

  Fragment-assisted hit investigation involving integrated HTS and fragment screening: Application to the identification of phosphodiesterase 10A (PDE10A) inhibitors

  摘要：

  Fragment-based drug design (FBDD) relies on direct elaboration of fragment hits and typically requires high resolution structural information to guide optimization. In fragment-assisted drug discovery (FADD), fragments provide information to guide selection and design but do not serve as starting points for elaboration. We describe FADD and high-throughput screening (HTS) campaign strategies conducted in parallel against PDE10A where fragment hit co-crystallography was not available. The fragment screen led to prioritized fragment hits (IC50's similar to 500 mu M), which were used to generate a hypothetical core scaffold. Application of this scaffold as a filter to HTS output afforded a 4 mu M hit, which, after preparation of a small number of analogs, was elaborated into a 16 nM lead. This approach highlights the strength of FADD, as fragment methods were applied despite the absence of co-crystallographical information to efficiently identify a lead compound for further optimization. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.10.100

文献信息

• Fragment-assisted hit investigation involving integrated HTS and fragment screening: Application to the identification of phosphodiesterase 10A (PDE10A) inhibitors
  作者：Jeffrey G. Varnes、Stefan Geschwindner、Christopher R. Holmquist、Janet Forst、Xia Wang、Niek Dekker、Clay W. Scott、Gaochao Tian、Michael W. Wood、Jeffrey S. Albert

  DOI：10.1016/j.bmcl.2015.10.100

  日期：2016.1

  Fragment-based drug design (FBDD) relies on direct elaboration of fragment hits and typically requires high resolution structural information to guide optimization. In fragment-assisted drug discovery (FADD), fragments provide information to guide selection and design but do not serve as starting points for elaboration. We describe FADD and high-throughput screening (HTS) campaign strategies conducted in parallel against PDE10A where fragment hit co-crystallography was not available. The fragment screen led to prioritized fragment hits (IC50's similar to 500 mu M), which were used to generate a hypothetical core scaffold. Application of this scaffold as a filter to HTS output afforded a 4 mu M hit, which, after preparation of a small number of analogs, was elaborated into a 16 nM lead. This approach highlights the strength of FADD, as fragment methods were applied despite the absence of co-crystallographical information to efficiently identify a lead compound for further optimization. (C) 2015 Elsevier Ltd. All rights reserved.