3-methyl-6-(phenylethynyl)-3H-imidazo[4,5-b]pyridine | 1264193-08-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: 3-methyl-6-(phenylethynyl)-3H-imidazo[4,5-b]pyridine
• 英文别名: 3-methyl-6-(2-phenylethynyl)imidazo[4,5-b]pyridine
• CAS: 1264193-08-9
• 化学式: C₁₅H₁₁N₃
• 分子量: 233.272
• InChiKey: GOZOOQBAFUIOQS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  30.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  苯基乙炔三丁基锡 、 6-溴-3-甲基-3H-咪唑并[4,5-b]吡啶 在 四(三苯基膦)钯 作用下， 以 甲苯 为溶剂， 反应 0.75h， 以86%的产率得到3-methyl-6-(phenylethynyl)-3H-imidazo[4,5-b]pyridine
  参考文献：
  名称：

  Discovery of novel positive allosteric modulators of the metabotropic glutamate receptor 5 (mGlu5)

  摘要：

  Novel in vitro mGlu(5) positive allosteric modulators with good potency, solubility, and low lipophilicity are described. Compounds were identified which did not rely on the phenylacetylene and carbonyl functionalities previously observed to be required for in vitro activity. Investigation of the allosteric binding requirements of a series of dihydroquinolinone analogs led to phenylacetylene azachromanone 4 (EC50 11.5 nM). Because of risks associated with potential metabolic and toxicological liabilities of the phenylacetylene, this moiety was successfully replaced with a phenoxymethyl group (27; EC50 156.3 nM). Derivation of a second-generation of mGlu(5) PAMs lacking a ketone carbonyl resulted in azaindoline (33), azabenzimidazole (36), and N-methyl 8-azaoxazine (39) phenylacetylenes. By scoping nitrogen substituents and phenylacetylene replacements in 39, we identified phenoxymethyl 8-azaoxazine 47 (EC50 50.1 nM) as a potent and soluble mGlu(5) PAM devoid of both undesirable phenylacetylene and carbonyl functionalities. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.027

文献信息

• METABOTROPIC GLUTAMATE RECEPTOR MODULATORS
  申请人：Henrich Markus

  公开号：US20120178742A1

  公开（公告）日：2012-07-12

  The invention relates to heterocyclic derivatives as well as their pharmaceutically acceptable salts. The invention further relates to a process for the preparation of such compounds. The compounds of the invention are mGluR5 modulators and are therefore useful for the control and prevention of acute and/or chronic neurological disorders.

  本发明涉及杂环衍生物及其药学上可接受的盐。本发明还涉及制备这种化合物的过程。本发明的化合物是mGluR5调节剂，因此可用于控制和预防急性和/或慢性神经系统疾病。
• Discovery of novel positive allosteric modulators of the metabotropic glutamate receptor 5 (mGlu5)
  作者：Jeffrey G. Varnes、Andrew P. Marcus、Russell C. Mauger、Scott R. Throner、Valerie Hoesch、Megan M. King、Xia Wang、Linda A. Sygowski、Nathan Spear、Reto Gadient、Dean G. Brown、James B. Campbell

  DOI：10.1016/j.bmcl.2011.01.027

  日期：2011.3

  Novel in vitro mGlu(5) positive allosteric modulators with good potency, solubility, and low lipophilicity are described. Compounds were identified which did not rely on the phenylacetylene and carbonyl functionalities previously observed to be required for in vitro activity. Investigation of the allosteric binding requirements of a series of dihydroquinolinone analogs led to phenylacetylene azachromanone 4 (EC50 11.5 nM). Because of risks associated with potential metabolic and toxicological liabilities of the phenylacetylene, this moiety was successfully replaced with a phenoxymethyl group (27; EC50 156.3 nM). Derivation of a second-generation of mGlu(5) PAMs lacking a ketone carbonyl resulted in azaindoline (33), azabenzimidazole (36), and N-methyl 8-azaoxazine (39) phenylacetylenes. By scoping nitrogen substituents and phenylacetylene replacements in 39, we identified phenoxymethyl 8-azaoxazine 47 (EC50 50.1 nM) as a potent and soluble mGlu(5) PAM devoid of both undesirable phenylacetylene and carbonyl functionalities. (C) 2011 Elsevier Ltd. All rights reserved.