(3-((4-fluorophenoxy)methyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)(4-fluorophenyl)methanone | 1384873-39-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: (3-((4-fluorophenoxy)methyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)(4-fluorophenyl)methanone
• 英文别名: [3-[(4-fluorophenoxy)methyl]-7,8-dihydro-5H-1,6-naphthyridin-6-yl]-(4-fluorophenyl)methanone
• CAS: 1384873-39-5
• 化学式: C₂₂H₁₈F₂N₂O₂
• 分子量: 380.394
• InChiKey: LOMPCLUTYIJQDZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  42.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-溴咪唑[1,2-A] 5,6,7,8-四氢-1,6-萘啶盐酸盐 在 sodium tetrahydroborate 、 四(三苯基膦)钯 、 偶氮二甲酸二异丙酯 、 臭氧 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 为溶剂， 反应 2.08h， 生成 (3-((4-fluorophenoxy)methyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)(4-fluorophenyl)methanone
  参考文献：
  名称：

  Tetrahydronaphthyridine and Dihydronaphthyridinone Ethers As Positive Allosteric Modulators of the Metabotropic Glutamate Receptor 5 (mGlu₅)

  摘要：

  Positive allosteric modulators (PAMs) of metabotropic glutamate receptor 5 (mGlu(5)) represent a promising therapeutic strategy for the treatment of schizophrenia. Starting from an acetylene-based lead from high throughput screening, an evolved bicyclic dihydronaphthyridinone was identified. We describe further refinements leading to both dihydronaphthyridinone and tetrahydronaphthyridine mGlu(5) PAMs containing an alkoxy-based linkage as an acetylene replacement. Exploration of several structural features including western pyridine ring isomers, positional amides, linker connectivity/position, and combinations thereof, reveal that these bicyclic modulators generally exhibit steep SAR and within specific subseries display a propensity for pharmacological mode switching at mGlu(5) as well as antagonist activity at mGlu(3). Structure-activity relationships within a dihydronaphthyridinone subseries uncovered 12c (VU0405372), a selective mGlu(5) PAM with good in vitro potency, low glutamate fold-shift, acceptable DMPK properties, and in vivo efficacy in an amphetamine-based model of psychosis.

  DOI：

  10.1021/jm500259z

文献信息

• DIHYDRONAPHTHYRIDINYL(ORGANO)METHANONE ANALOGS AS POSITIVE ALLOSTERIC MGLUR5 MODULATORS
  申请人：Conn P. Jeffrey

  公开号：US20120178776A1

  公开（公告）日：2012-07-12

  In one aspect, the invention relates to dihydronaphthyridinyl(organo)methanone analogs, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions. 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.

  在一方面，该发明涉及二氢萘啉基(有机)甲酮类似物、其衍生物和相关化合物，这些化合物可用作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；以及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。本摘要旨在作为在特定领域搜索的扫描工具，并不限制本发明。
• US8710074B2
  申请人：——

  公开号：US8710074B2

  公开（公告）日：2014-04-29
• [EN] DIHYDRONAPHTHYRIDINYL(ORGANO)METHANONE ANALOGS AS POSITIVE ALLOSTERIC MGLUR5 MODULATORS<br/>[FR] ANALOGUES DE DIHYDRONAPHTYRIDINYL-(ORGANO)MÉTHANONE UTILISABLES COMME MODULATEURS ALLOSTÉRIQUES POSITIFS DE MGLUR5
  申请人：UNIV VANDERBILT

  公开号：WO2012097182A1

  公开（公告）日：2012-07-19

  In one aspect, the invention relates to dihydronaphthyridinyl(organo)methanone analogs, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions. 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.
• Tetrahydronaphthyridine and Dihydronaphthyridinone Ethers As Positive Allosteric Modulators of the Metabotropic Glutamate Receptor 5 (mGlu₅)
  作者：Mark Turlington、Chrysa Malosh、Jon Jacobs、Jason T. Manka、Meredith J. Noetzel、Paige N. Vinson、Satyawan Jadhav、Elizabeth J. Herman、Hilde Lavreysen、Claire Mackie、José M. Bartolomé-Nebreda、Susana Conde-Ceide、M. Luz Martín-Martín、Han Min Tong、Silvia López、Gregor J. MacDonald、Thomas Steckler、J. Scott Daniels、C. David Weaver、Colleen M. Niswender、Carrie K. Jones、P. Jeffrey Conn、Craig W. Lindsley、Shaun R. Stauffer

  DOI：10.1021/jm500259z

  日期：2014.7.10

  Positive allosteric modulators (PAMs) of metabotropic glutamate receptor 5 (mGlu(5)) represent a promising therapeutic strategy for the treatment of schizophrenia. Starting from an acetylene-based lead from high throughput screening, an evolved bicyclic dihydronaphthyridinone was identified. We describe further refinements leading to both dihydronaphthyridinone and tetrahydronaphthyridine mGlu(5) PAMs containing an alkoxy-based linkage as an acetylene replacement. Exploration of several structural features including western pyridine ring isomers, positional amides, linker connectivity/position, and combinations thereof, reveal that these bicyclic modulators generally exhibit steep SAR and within specific subseries display a propensity for pharmacological mode switching at mGlu(5) as well as antagonist activity at mGlu(3). Structure-activity relationships within a dihydronaphthyridinone subseries uncovered 12c (VU0405372), a selective mGlu(5) PAM with good in vitro potency, low glutamate fold-shift, acceptable DMPK properties, and in vivo efficacy in an amphetamine-based model of psychosis.