N-(4-bromo-3-cyanophenyl)-2-picolinamide

• 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: N-(4-bromo-3-cyanophenyl)-2-picolinamide
• 英文别名: N-(4-bromo-3-cyanophenyl)pyridine-2-carboxamide
• 化学式: C₁₃H₈BrN₃O
• 分子量: 302.13
• InChiKey: IWENPVLCRBESMO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  65.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(4-bromo-3-cyanophenyl)-2-picolinamide 在 四(三苯基膦)钯 、 碘 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 生成 N-(3-cyano-4-iodophenyl)-2-picolinamide
  参考文献：
  名称：

  Re-exploring the N-phenylpicolinamide derivatives to develop mGlu4 ligands with improved affinity and in vitro microsomal stability

  摘要：

  In recent years, mGlu(4) has received great attention and research effort because of the potential benefits of mGlu(4) activation in treating numerous brain disorders, such as Parkinson's disease (PD). Many positive allosteric modulators of mGlu(4) have been developed. To better understand the role of mGlu(4) in healthy and disease conditions, we are interested in developing an mGlu(4) selective radioligand for in vivo studies. Thus, we had synthesized and studied [C-11]2 as a PET tracer for mGlu(4), which demonstrated some promising features as a PET radioligand as well as the limitation need to be improved. In order to develop an mGlu(4) ligand with enhanced affinity and improved metabolic stability, we have modified, synthesized and evaluated a series of new N-phenylpicolinamide derivatives. The SAR study has discovered a number of compounds with low nM affinity to mGlu(4). The dideuteriumfluoromethoxy modified compound 24 is identified as a very promising mGlu(4) ligand, which has demonstrated enhanced affinity, improved in vitro microsomal stability, good selectivity and good permeability. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.07.031
• 作为产物：
  描述：

  2-吡啶甲酸 、 5-氨基-2-溴苯腈 在 氯化亚砜 、 三乙胺 作用下， 以 苯 、 四氢呋喃 为溶剂， 以69.1%的产率得到N-(4-bromo-3-cyanophenyl)-2-picolinamide
  参考文献：
  名称：

  Re-exploring the N-phenylpicolinamide derivatives to develop mGlu4 ligands with improved affinity and in vitro microsomal stability

  摘要：

  In recent years, mGlu(4) has received great attention and research effort because of the potential benefits of mGlu(4) activation in treating numerous brain disorders, such as Parkinson's disease (PD). Many positive allosteric modulators of mGlu(4) have been developed. To better understand the role of mGlu(4) in healthy and disease conditions, we are interested in developing an mGlu(4) selective radioligand for in vivo studies. Thus, we had synthesized and studied [C-11]2 as a PET tracer for mGlu(4), which demonstrated some promising features as a PET radioligand as well as the limitation need to be improved. In order to develop an mGlu(4) ligand with enhanced affinity and improved metabolic stability, we have modified, synthesized and evaluated a series of new N-phenylpicolinamide derivatives. The SAR study has discovered a number of compounds with low nM affinity to mGlu(4). The dideuteriumfluoromethoxy modified compound 24 is identified as a very promising mGlu(4) ligand, which has demonstrated enhanced affinity, improved in vitro microsomal stability, good selectivity and good permeability. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.07.031

文献信息

• Re-exploring the N-phenylpicolinamide derivatives to develop mGlu4 ligands with improved affinity and in vitro microsomal stability
  作者：Zhaoda Zhang、Kun-Eek Kil、Pekka Poutiainen、Ji-Kyung Choi、Hye-Jin Kang、Xi-Ping Huang、Bryan L. Roth、Anna-Liisa Brownell

  DOI：10.1016/j.bmcl.2015.07.031

  日期：2015.9

  In recent years, mGlu(4) has received great attention and research effort because of the potential benefits of mGlu(4) activation in treating numerous brain disorders, such as Parkinson's disease (PD). Many positive allosteric modulators of mGlu(4) have been developed. To better understand the role of mGlu(4) in healthy and disease conditions, we are interested in developing an mGlu(4) selective radioligand for in vivo studies. Thus, we had synthesized and studied [C-11]2 as a PET tracer for mGlu(4), which demonstrated some promising features as a PET radioligand as well as the limitation need to be improved. In order to develop an mGlu(4) ligand with enhanced affinity and improved metabolic stability, we have modified, synthesized and evaluated a series of new N-phenylpicolinamide derivatives. The SAR study has discovered a number of compounds with low nM affinity to mGlu(4). The dideuteriumfluoromethoxy modified compound 24 is identified as a very promising mGlu(4) ligand, which has demonstrated enhanced affinity, improved in vitro microsomal stability, good selectivity and good permeability. (C) 2015 Elsevier Ltd. All rights reserved.