2-phenyl-1,4-dihydro-1,6-naphthyridin-4-one | 1616976-52-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-phenyl-1,4-dihydro-1,6-naphthyridin-4-one
• 英文别名: 2-phenyl-1,6-naphthyridin-4(1H)-one；2-phenyl-1H-1,6-naphthyridin-4-one
• CAS: 1616976-52-3；385784-21-4
• 化学式: C₁₄H₁₀N₂O
• 分子量: 222.246
• InChiKey: CODGTSDGOGABHJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-phenyl-1,4-dihydro-1,6-naphthyridin-4-one 、 2-bromo-N-methyl-N-phenylpropanamide 在 caesium carbonate 作用下， 以 丙酮 为溶剂， 反应 19.0h， 以9%的产率得到N-methyl-N-phenyl-2-[(2-phenyl-1,6-naphthyridin-4-yl)oxy]propanamide
  参考文献：
  名称：

  Development of N-Methyl-(2-arylquinolin-4-yl)oxypropanamides as Leads to PET Radioligands for Translocator Protein (18 kDa)

  摘要：

  Translocator protein (18 kDa), known as TSPO, is a recognized biomarker of neuroinflammation. Radioligands with PET accurately quantify TSPO in neuroinflammatory conditions. However, the existence of three human TSPO genotypes that show differential affinity to almost all useful TSPO PET radioligands hampers such studies. There is an unmet need for genotype-insensitive, high-affinity, and moderately lipophilic TSPO ligands that may serve as leads for PET radioligand development. To address this need, we varied the known high-affinity TSPO ligand (l)-N,N-diethyl-2-methyl-3-(2-phenylquinolin-4-yl)propanamide in its aryl scaffold, side chain tether, and pendant substituted amido group while retaining an N-methyl group as a site for labeling with carbon-11. From this effort, oxygen-tethered N-methyl-aryloxypropanamides emerged as new high-affinity TSPO ligands with attenuated lipophilicity, including one example with attractive properties for PET radioligand development, namely N-methyl-N-phenyl-2-{[2-(pyridin-2-yl)quinolin-4-yl]oxy}propanamide (22a; rat K-i = 0.10 nM; human TSPO genotypes K-i = 1.4 nM; clogD = 4.18).

  DOI：

  10.1021/jm5007947
• 作为产物：
  描述：

  4-氨基-3-溴吡啶 在 4-二甲氨基吡啶 、 正丁基锂 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正己烷 、 二氯甲烷 为溶剂， 反应 4.25h， 生成 2-phenyl-1,4-dihydro-1,6-naphthyridin-4-one
  参考文献：
  名称：

  Development of N-Methyl-(2-arylquinolin-4-yl)oxypropanamides as Leads to PET Radioligands for Translocator Protein (18 kDa)

  摘要：

  Translocator protein (18 kDa), known as TSPO, is a recognized biomarker of neuroinflammation. Radioligands with PET accurately quantify TSPO in neuroinflammatory conditions. However, the existence of three human TSPO genotypes that show differential affinity to almost all useful TSPO PET radioligands hampers such studies. There is an unmet need for genotype-insensitive, high-affinity, and moderately lipophilic TSPO ligands that may serve as leads for PET radioligand development. To address this need, we varied the known high-affinity TSPO ligand (l)-N,N-diethyl-2-methyl-3-(2-phenylquinolin-4-yl)propanamide in its aryl scaffold, side chain tether, and pendant substituted amido group while retaining an N-methyl group as a site for labeling with carbon-11. From this effort, oxygen-tethered N-methyl-aryloxypropanamides emerged as new high-affinity TSPO ligands with attenuated lipophilicity, including one example with attractive properties for PET radioligand development, namely N-methyl-N-phenyl-2-{[2-(pyridin-2-yl)quinolin-4-yl]oxy}propanamide (22a; rat K-i = 0.10 nM; human TSPO genotypes K-i = 1.4 nM; clogD = 4.18).

  DOI：

  10.1021/jm5007947

文献信息

• Direct Synthesis of 2-Aryl-4-quinolones via Transition-Metal-Free Intramolecular Oxidative C(sp³)–H/C(sp³)–H Coupling
  作者：Wei Hu、Jian-Ping Lin、Li-Rui Song、Ya-Qiu Long

  DOI：10.1021/acs.orglett.5b00248

  日期：2015.3.6

  A novel, metal-free oxidative intramolecular Mannich reaction was developed between secondary amines and unmodified ketones, affording a simple and direct access to a broad range of 2-arylquinolin-4(1H)-ones through C(sp3)–H activation/C(sp3)–C(sp3) bond formation from readily available N-arylmethyl-2-aminophenylketones, using TEMPO as the oxidant and KOtBu as the base.

  在仲胺和未改性的酮之间开发了一种新颖的，无金属的氧化性分子内曼尼希反应，可通过C（sp 3）-H活化简单直接地获得广泛的2-芳基喹啉4（1 H）-酮。/ C（sp 3）–C（sp 3）键由易于获得的N-芳基甲基-2-氨基苯基酮形成，使用TEMPO作为氧化剂，KO t Bu作为碱。
• Aryl fused substituted 4-oxy-pyridines
  申请人：——

  公开号：US20020035121A1

  公开（公告）日：2002-03-21

  Disclosed are compounds of the formula: 1 wherein X, Q, W and 2 are as defined herein. These compounds are agonists, antagonists or inverse agonists for GABA A brain receptors or prodrugs of agonists, antagonists or inverse agonists for GABA A brain receptors and are therefore useful in the diagnosis and treatment of anxiety, depression, Down Syndrome, sleep and seizure disorders, overdose with benzodiazepine drugs and for enhancement of memory. Pharmaceutical compositions, including packaged pharmaceutical compositions, are further provided. Compounds of the invention are also useful as probes for the localization of GABA A receptors in tissue samples.

  本发明揭示了化合物的公式：1，其中X，Q，W和2如定义所述。这些化合物是GABAA脑受体的激动剂，拮抗剂或反向激动剂，或者是GABAA脑受体激动剂，拮抗剂或反向激动剂的前药，因此在焦虑，抑郁，唐氏综合症，睡眠和癫痫障碍，苯二氮卓类药物过量和记忆增强的诊断和治疗中有用。此外，还提供了包括包装的制药组合物在内的制药组合物。本发明的化合物还可用作组织样本中GABAA受体定位的探针。
• US6828329B2
  申请人：——

  公开号：US6828329B2

  公开（公告）日：2004-12-07
• US7371752B2
  申请人：——

  公开号：US7371752B2

  公开（公告）日：2008-05-13
• [EN] ARYL FUSED SUBSTITUTED 4-OXY-PYRIDINES<br/>[FR] 4-OXY-PYRIDINES SUBSTITUEES A FUSION ARYLE
  申请人：NEUROGEN CORP

  公开号：WO2002000623A2

  公开（公告）日：2002-01-03

  Disclosed are compounds of the formula (I): wherein X, Q, W and formula (II) are as defined herein. These compounds are agonists, antagonists or inverse agonists for GABAA brain receptors or prodrugs of agonists, antagonists or inverse agonists of GABAA brain receptors and are therefore useful in the diagnosis and treatment of anxiety, depression, Down Syndrome, sleep and seizure disorders, overdose with benzodiazepine drugs and for enhancement of memory. Pharmaceutical compositions, including packaged pharmaceutical compositions, are further provided. Compounds of the invention are also useful as probes for the localization of GABAA receptors in tissue samples.