1-(2-(phenoxymethyl)-6,7-dihydrooxazolo[5,4-c]pyridin-5(4H)-yl)ethan-1-one | 1363281-86-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-(2-(phenoxymethyl)-6,7-dihydrooxazolo[5,4-c]pyridin-5(4H)-yl)ethan-1-one
• 英文别名: 5-acetyl-4,5,6,7-tetrahydro-2-(phenoxymethyl)-oxazolo[5,4-c]pyridine；1-[2-(phenoxymethyl)-6,7-dihydro-4H-[1,3]oxazolo[5,4-c]pyridin-5-yl]ethanone
• CAS: 1363281-86-0
• 化学式: C₁₅H₁₆N₂O₃
• 分子量: 272.304
• InChiKey: LUXPYHUBHJRCSI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  55.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  ethyl 2-(phenoxymethyl)-6,7-dihydro-4H-oxazolo[5,4-c]pyridine-5-carboxylate 在 三乙胺 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 60.0h， 生成 1-(2-(phenoxymethyl)-6,7-dihydrooxazolo[5,4-c]pyridin-5(4H)-yl)ethan-1-one
  参考文献：
  名称：

  Discovery of VU0409551/JNJ-46778212: An mGlu₅ Positive Allosteric Modulator Clinical Candidate Targeting Schizophrenia

  摘要：

  Herein, we report the structure activity relationship of a novel series of (2(phenoxymethyl)-6,7-dihydrooxazolo[5,4-c]pyridine-5(4H)-yl(aryl)methanones as potent, selective, and orally bioavailable metabotropic glutamate receptor subtype 5 (mGlu(5)) positive allosteric modulators (PAMs). On the basis of its robust in vitro potency and in vivo efficacy in multiple preclinical models of multiple domains of schizophrenia, coupled with a good DMPK profile and an acceptable therapeutic window, 17a (VU0409551/JNJ-46778212) was selected as a candidate for further development.

  DOI：

  10.1021/acsmedchemlett.5b00181

文献信息

• [EN] BICYCLIC OXAZOLE AND THIAZOLE COMPOUNDS AND THEIR USE AS ALLOSTERIC MODULATORS OF MGLUR5 RECEPTORS<br/>[FR] COMPOSÉS BICYCLIQUES D'OXAZOLE ET DE THIAZOLE ET LEUR UTILISATION EN TANT QUE MODULATEURS ALLOSTÉRIQUES DES RÉCEPTEURS MGLUR5
  申请人：UNIV VANDERBILT

  公开号：WO2012031024A1

  公开（公告）日：2012-03-08

  In one aspect, the invention relates to novel bicyclic oxazole and thiazole compounds which are positive allosteric modulators of the metabotropic glutamate receptor subtype 5 ("mGluR5"); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions; and methods for the treatment or prevention of disorders associated with glutamate dysfunction and diseases in which the mGluR5 subtype of receptors is involved. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  在一个方面，该发明涉及新型的双环氧唑和噻唑化合物，它们是代谢型谷氨酸受体亚型5（"mGluR5"）的阳性变构调节剂；制备这些化合物的合成方法；包含这些化合物的药物组合物；使用这些化合物和组合物治疗与谷氨酸功能障碍相关的神经和精神疾病的方法；以及治疗或预防与谷氨酸功能障碍相关的疾病以及mGluR5受体亚型参与的疾病的方法。本摘要旨在作为在特定领域进行搜索的扫描工具，并不意味着对本发明的限制。
• BICYCLIC OXAZOLE AND THIAZOLE COMPOUNDS AND THEIR USE AS ALLOSTERIC MODULATORS OF MGLUR5 RECEPTORS
  申请人：Conn P. Jeffrey

  公开号：US20130261107A1

  公开（公告）日：2013-10-03

  In one aspect, the invention relates to novel bicyclic oxazole and thiazole compounds which are positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (“mGluR5”); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions; and methods for the treatment or prevention of disorders associated with glutamate dysfunction and diseases in which the mGluR5 subtype of receptors is involved. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  该发明涉及一种新型双环氧唑和噻唑化合物，它们是代谢型谷氨酸受体亚型5（“mGluR5”）的正向变构调节剂；制备这些化合物的合成方法；包含这些化合物的药物组合物；使用这些化合物和组合物治疗与谷氨酸功能失调相关的神经和精神障碍的方法；以及用于治疗或预防与谷氨酸功能失调相关的疾病和mGluR5受体亚型参与的疾病的方法。本摘要旨在作为搜索特定技术领域的扫描工具，并不限制本发明。
• US9090632B2
  申请人：——

  公开号：US9090632B2

  公开（公告）日：2015-07-28
• Discovery of VU0409551/JNJ-46778212: An mGlu₅ Positive Allosteric Modulator Clinical Candidate Targeting Schizophrenia
  作者：Susana Conde-Ceide、Carlos M. Martínez-Viturro、Jesús Alcázar、Pedro M. Garcia-Barrantes、Hilde Lavreysen、Claire Mackie、Paige N. Vinson、Jerri M. Rook、Thomas M. Bridges、J. Scott Daniels、Anton Megens、Xavier Langlois、Wilhelmus H. Drinkenburg、Abdellah Ahnaou、Colleen M. Niswender、Carrie K. Jones、Gregor J. Macdonald、Thomas Steckler、P. Jeffrey Conn、Shaun R. Stauffer、José Manuel Bartolomé-Nebreda、Craig W. Lindsley

  DOI：10.1021/acsmedchemlett.5b00181

  日期：2015.6.11

  Herein, we report the structure activity relationship of a novel series of (2(phenoxymethyl)-6,7-dihydrooxazolo[5,4-c]pyridine-5(4H)-yl(aryl)methanones as potent, selective, and orally bioavailable metabotropic glutamate receptor subtype 5 (mGlu(5)) positive allosteric modulators (PAMs). On the basis of its robust in vitro potency and in vivo efficacy in multiple preclinical models of multiple domains of schizophrenia, coupled with a good DMPK profile and an acceptable therapeutic window, 17a (VU0409551/JNJ-46778212) was selected as a candidate for further development.