N-(3-hydroxyphenyl)picolinamide | 1038242-28-2

• 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-(3-hydroxyphenyl)picolinamide
• 英文别名: N-(3-hydroxyphenyl)-2-picolinamide；N-(3-hydroxyphenyl)pyridine-2-carboxamide
• CAS: 1038242-28-2
• 化学式: C₁₂H₁₀N₂O₂
• mdl: MFCD11167713
• 分子量: 214.224
• InChiKey: BDLISZAPWMXVEJ-UHFFFAOYSA-N

物化性质

• 沸点：
  321.1±22.0 °C(predicted)
• 密度：
  1.339±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  62.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(3-hydroxyphenyl)picolinamide 、 fluoromethyl-d2 4-methylbenzenesulfonate 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 48.0h， 以44%的产率得到N-(3-(fluoromethoxy-d2)phenyl)-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：

  N-(3-methoxyphenyl)picolinamide 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 以55%的产率得到N-(3-hydroxyphenyl)picolinamide
  参考文献：
  名称：

  Syntheses, characterization, and anti-cancer activities of pyridine-amide based compounds containing appended phenol or catechol groups

  摘要：

  合成了几种带有酚/儿茶酚基团的吡啶酰胺化合物。这些化合物包括已保护或未保护的酚/儿茶酚基团，并提供了吡啶、酰胺和酚/儿茶酚官能团。所有化合物均已通过多种光谱方法、元素分析、热学研究和结晶学进行了充分的表征。所有化合物的生物活性均已得到研究，其中少数化合物在剂量依赖性方式下显著降低了T98G细胞的代谢活力、生长和克隆能力。在T98G细胞中观察到了ROS的积累，这些细胞显示出了受损的氧化还原状态，这一点从增加的细胞Caspase 3/7活性和微核的形成中可以明显看出。计算机模型药代动力学研究显示，所有化合物均具有良好的生物利用度、水溶性和其他类药物参数。由于以下原因，少数化合物被确定为未来研究的潜在先导分子：（a）对T98G脑、H-460肺和SNU-80甲状腺癌细胞具有高活性；（b）对非恶性HEK和MRC-5细胞具有低细胞毒性；（c）基于计算机模型的评估显示低毒性风险；（d）根据Lipinski的“五规则”药代动力学参数显示良好的理论口服生物利用度；以及（e）更好的药物相似性和药物评分值。

  DOI：

  10.1007/s12039-014-0671-3

文献信息

• Structure–activity relationship investigation of benzamide and picolinamide derivatives containing dimethylamine side chain as acetylcholinesterase inhibitors
  作者：Xiao-hui Gao、Lin-bo Liu、Hao-ran Liu、Jing-jing Tang、Lu Kang、Hongnian Wu、Peiwu Cui、Jianye Yan

  DOI：10.1080/14756366.2017.1399885

  日期：2018.1.1

  A series of benzamide and picolinamide derivatives containing dimethylamine side chain (4a-4c and 7a-7i) were synthesised and evaluated for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity in vitro. Structure-activity relationship investigation revealed that the substituted position of dimethylamine side chain markedly influenced the inhibitory activity and selectivity

  合成了一系列含有二甲胺侧链的苯甲酰胺和吡啶甲酰胺衍生物（4a-4c和7a-7i），并在体外评估了其对乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）的抑制活性。结构-活性关系研究表明，二甲胺侧链的取代位置显着影响了对AChE和BChE的抑制活性和选择性。另外，似乎吡啶甲酰胺酰胺衍生物的生物活性强于苯甲酰胺衍生物。其中，化合物7a显示出最有效的AChE抑制活性（IC50：2.49±0.19μM）和相对于BChE的对AChE的最高选择性（比率：99.40）。酶动力学研究表明，化合物7a对AChE表现出混合型抑制作用。
• NOVEL AMIDO DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS
  申请人：Boléa Christelle

  公开号：US20100137336A1

  公开（公告）日：2010-06-03

  The present invention relates to novel compounds of Formula (I), wherein X 1 , X 2 , X 3 , X 4 , A m and B n are defined as in Formula (I); invention compounds are modulators of metabotropic glutamate receptors—subtype 4 (“mGluR4”) which are useful for the treatment or prevention of central nervous system disorders as well as other disorders modulated by mGluR4 receptors. The invention is also directed to pharmaceutical compositions and the use of such compounds in the manufacture of medicaments, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR4 is involved.

  本发明涉及公式（I）的新化合物，其中X1、X2、X3、X4、A和Bn的定义如公式（I）中所述；发明化合物是代谢型谷氨酸受体-亚型4（“mGluR4”）的调节剂，可用于治疗或预防中枢神经系统疾病以及其他受mGluR4受体调节的疾病。本发明还涉及制药组合物及其在制造药物方面的使用，以及在涉及mGluR4的疾病的预防和治疗中使用此类化合物。
• Novel amido derivatives and their use as positive allosteric modulators of metabotropic glutamate receptors
  申请人：Bolea Christelle

  公开号：US20110257182A1

  公开（公告）日：2011-10-20

  The present invention relates to novel compounds of Formula (I), wherein X 1 , X 2 , X 3 , X 4 , A m and B n are defined as in Formula (I); invention compounds are modulators of metabotropic glutamate receptors—subtype 4 (“mGluR4”) which are useful for the treatment or prevention of central nervous system disorders as well as other disorders modulated by mGluR4 receptors. The invention is also directed to pharmaceutical compositions and the use of such compounds in the manufacture of medicaments, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR4 is involved.

  本发明涉及一种新型的化合物，其化学式为(I)，其中X1、X2、X3、X4、A和Bn的定义如化学式(I)中所示；发明的化合物是代谢型谷氨酸受体亚型4（“mGluR4”）的调节剂，可用于治疗或预防中枢神经系统疾病以及其他由mGluR4受体调节的疾病。本发明还涉及制药组合物以及使用这些化合物制备药物的方法，以及使用这些化合物预防和治疗涉及mGluR4的疾病的方法。
• Amido derivatives and their use as positive allosteric modulators of metabotropic glutamate receptors
  申请人：Addex Pharma, SA

  公开号：US08524726B2

  公开（公告）日：2013-09-03

  The present invention relates to novel compounds of Formula (I), wherein X1, X2, X3, X4, Am and Bn are defined as in Formula (I); invention compounds are modulators of metabotropic glutamate receptors—subtype 4 (“mGluR4”) which are useful for the treatment or prevention of central nervous system disorders as well as other disorders modulated by mGluR4 receptors. The invention is also directed to pharmaceutical compositions and the use of such compounds in the manufacture of medicaments, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR4 is involved.

  本发明涉及公式（I）的新化合物，其中X1、X2、X3、X4、Am和Bn的定义如公式（I）中所示；发明化合物是代谢型谷氨酸受体-亚型4（“mGluR4”）的调节剂，可用于治疗或预防中枢神经系统疾病以及其他由mGluR4受体调节的疾病。本发明还涉及制药组合物以及使用该化合物制造药品的用途，以及使用该化合物预防和治疗mGluR4参与的这些疾病的用途。
• [EN] AMIDO DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS<br/>[FR] NOUVEAUX DÉRIVÉS AMIDO ET LEUR UTILISATION EN TANT QUE MODULATEURS ALLOSTÉRIQUES POSITIFS DES RÉCEPTEURS MÉTABOTROPIQUES DU GLUTAMATE
  申请人：ADDEX PHARMACEUTICALS SA

  公开号：WO2009010454A3

  公开（公告）日：2009-03-05