6-(4-甲基苯氧基)吡啶-3-甲腈 | 99902-75-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 6-(4-甲基苯氧基)吡啶-3-甲腈
• 英文名称: 6-(p-tolyloxy)nicotinonitrile
• 英文别名: 3-Pyridinecarbonitrile, 6-(4-methylphenoxy)-；6-(4-methylphenoxy)pyridine-3-carbonitrile
• CAS: 99902-75-7
• 化学式: C₁₃H₁₀N₂O
• mdl: MFCD09939823
• 分子量: 210.235
• InChiKey: IZHLMEHEGRNQMP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.076
• 拓扑面积：
  45.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(4-甲基苯氧基)吡啶-3-甲腈 在 sodium tetrahydroborate 、 nickel(II) chloride hexahydrate 、 二碳酸二叔丁酯 、 1-丙基磷酸酐 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 为溶剂， 反应 7.5h， 生成 4-chloro-3-ethyl-1-methyl-N-((6-(p-tolyloxy)pyridin-3-yl)methyl)-1H-pyrazole-5-carboxamide
  参考文献：
  名称：

  Structure–Activity Relationship Studies of Tolfenpyrad Reveal Subnanomolar Inhibitors ofHaemonchus contortusDevelopment

  摘要：

  Recently, we have discovered that the registered pesticide, tolfenpyrad, unexpectedly and potently inhibits the development of the L4 larval stage of the parasitic nematode Haemonchus contortus with an IC50 value of 0.03 mu M while displaying good selectivity, with an IC50 of 37.9 mu M for cytotoxicity. As a promising molecular template for medicinal chemistry optimization, we undertook anthelmintic structure-activity relationships for this chemical. Modifications of the left-hand side (LHS), right-hand side (RHS), and middle section of the scaffold were explored to produce a set of 57 analogues. Analogues 25, 29, and 33 were shown to be the most potent compounds of the series, with IC50 values at a subnanomolar level of potency against the chemotherapeutically relevant fourth larval (L4) stage of H. contortus. Selected compounds from the series also showed promising activity against a panel of other different parasitic nematodes, such as hookworms and whipworms.

  DOI：

  10.1021/acs.jmedchem.8b01789
• 作为产物：
  描述：

  6-氯-3-氰基吡啶 、 对甲酚 在 sodium hydride 作用下， 以 二甲基亚砜 为溶剂， 生成 6-(4-甲基苯氧基)吡啶-3-甲腈
  参考文献：
  名称：

  取代的苯氧基苯和苯氧基吡啶的抗小核糖核酸病毒活性。

  摘要：

  制备苯氧基苯和苯氧基吡啶，并测试取代基对抗小核糖核酸病毒活性的影响。最具活性的化合物2-（3,4-二氯苯氧基）-5-硝基苯甲腈（8）具有广谱抗幽门螺杆菌活性。分别在感染前和感染期间口服给予的化合物8和几种类似物可保护小鼠免受柯萨奇病毒A21致命的攻击。

  DOI：

  10.1021/jm00153a020

文献信息

• Antipicornavirus activity of substituted phenoxybenzenes and phenoxypyridines
  作者：Lowell D. Markley、Yulan C. Tong、Jacqueline K. Dulworth、David L. Steward、Christopher T. Goralski、Howard Johnston、Steven G. Wood、Anna P. Vinogradoff、Thomas M. Bargar

  DOI：10.1021/jm00153a020

  日期：1986.3

  Phenoxybenzenes and phenoxypyridines were prepared and tested for the effect of substituents on antipicornavirus activity. The most active compound, 2-(3,4-dichlorophenoxy)-5-nitrobenzonitrile (8), demonstrated broad-spectrum antipicornavirus activity. Compound 8 and several analogues each given orally prior to and during infection protected mice against an otherwise lethal challenge with coxsackievirus

  制备苯氧基苯和苯氧基吡啶，并测试取代基对抗小核糖核酸病毒活性的影响。最具活性的化合物2-（3,4-二氯苯氧基）-5-硝基苯甲腈（8）具有广谱抗幽门螺杆菌活性。分别在感染前和感染期间口服给予的化合物8和几种类似物可保护小鼠免受柯萨奇病毒A21致命的攻击。
• MARKLEY, L. D.;TONG, Y. C.;DULWORTH, J. K.;STEWARD, D. L.;GORALSKI, C. T.+, J. MED. CHEM., 1986, 29, N 3, 427-433
  作者：MARKLEY, L. D.、TONG, Y. C.、DULWORTH, J. K.、STEWARD, D. L.、GORALSKI, C. T.+

  DOI：——

  日期：——
• 1,4-DISUBSTITUTED 3-CYANO-PYRIDONE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2-RECEPTORS
  申请人：Janssen Pharmaceuticals, Inc.

  公开号：EP1994004B1

  公开（公告）日：2012-08-01
• 1, 4-DISUBSTITUTED 3-CYANO-PYRIDONE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2-RECEPTORS
  申请人：Imogai Hassan Julien

  公开号：US20100166655A1

  公开（公告）日：2010-07-01

  The present invention relates to novel compounds, in particular novel pyridinone derivatives according to Formula (I) wherein all radicals are defined in the application and claims. The compounds according to the invention are positive allosteric modulators of metabotropic receptors-subtype 2 (“mGluR2”) which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. In particular, such diseases are central nervous system disorders selected from the group of anxiety, schizophrenia, migraine, depression, and epilepsy. The invention is also directed to pharmaceutical compositions and processes to prepare such compounds and compositions, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR2 is involved.
• 1, 4-Disubstituted 3-Cyano-Pyridone Derivatives and Their Use As Positive Allosteric Modulators of MGLUR2-Receptors
  申请人：JANSSEN PHARMACEUTICALS, INC.

  公开号：US20140315903A1

  公开（公告）日：2014-10-23

  The present invention relates to novel compounds, in particular novel pyridinone derivatives according to Formula (I) wherein all radicals are defined in the application and claims. The compounds according to the invention are positive allosteric modulators of metabotropic receptors—subtype 2 (“mGluR2”) which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. In particular, such diseases are central nervous system disorders selected from the group of anxiety, schizophrenia, migraine, depression, and epilepsy. The invention is also directed to pharmaceutical compositions and processes to prepare such compounds and compositions, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR2 is involved.