6-(4-甲酰基苯氧基)吡啶-3-甲酰胺 | 676494-70-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 6-(4-甲酰基苯氧基)吡啶-3-甲酰胺
• 英文名称: 6-(4-formylphenoxy)pyridine-3-carboxamide
• 英文别名: 6-(4-formyl-phenoxy)-nicotinamide
• CAS: 676494-70-5
• 化学式: C₁₃H₁₀N₂O₃
• 分子量: 242.234
• InChiKey: WMRYYTSBKKACAN-UHFFFAOYSA-N

物化性质

• 沸点：
  465.7±40.0 °C(Predicted)
• 密度：
  1.319±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  82.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(4-甲酰基苯氧基)吡啶-3-甲酰胺 在 溶剂黄146 、 [双(2-甲氧基乙基)胺]三氟化硫 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 0.08h， 生成 6-[4-[ (3,3-dimethyl-2-phenyl-azetidin-1-yl)methyl]phenoxy]pyridine-3-carboxamide
  参考文献：
  名称：

  Discovery of Aminobenzyloxyarylamides as κ Opioid Receptor Selective Antagonists: Application to Preclinical Development of a κ Opioid Receptor Antagonist Receptor Occupancy Tracer

  摘要：

  Arylphenylpyrrolidinylmethylphenoxybenzamides were found to have high affinity and selectivity for K opioid receptors. On the basis of receptor binding assays in Chinese hamster ovary (CHO) cells expressing cloned human opioid receptors, (S)-3-fluoro-4-(4-((2-(3-fluorophenyppyrrolidin-1-yl)methyl)phenoxy)benzamide (25) had a K-i = 0.565 nM for kappa opioid receptor binding while having a K-i = 35.8 nM for mu opioid receptors and a K-i = 211 nM for delta opioid receptor binding. Compound 25 was also a potent antagonist of K opioid receptors when tested in vitro using a [S-35]-guanosine 5'O-[3-thiotriphosphate] ([S-35]GTP-gamma-S) functional assay in CHO cells expressing cloned human opioid receptors. Compounds were also evaluated for potential use as receptor occupancy tracers. Tracer evaluation was done in vivo, using liquid chromatography-tandem mass spectrometry (LC/MS/MS) methods, precluding the need for radiolabeling. (S)-3-Chloro-4-(4-((2-(pyridine-3-yl(pyrrolidin-1-yl)methyl)phenoxy)benzamide (18) was found to have favorable properties for a tracer for receptor occupancy, including good specific versus nonspecific binding and good brain uptake.

  DOI：

  10.1021/jm200789r
• 作为产物：
  描述：

  6-氟-烟腈 在 双氧水 、 potassium carbonate 作用下， 以 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 6-(4-甲酰基苯氧基)吡啶-3-甲酰胺
  参考文献：
  名称：

  Discovery of Aminobenzyloxyarylamides as κ Opioid Receptor Selective Antagonists: Application to Preclinical Development of a κ Opioid Receptor Antagonist Receptor Occupancy Tracer

  摘要：

  Arylphenylpyrrolidinylmethylphenoxybenzamides were found to have high affinity and selectivity for K opioid receptors. On the basis of receptor binding assays in Chinese hamster ovary (CHO) cells expressing cloned human opioid receptors, (S)-3-fluoro-4-(4-((2-(3-fluorophenyppyrrolidin-1-yl)methyl)phenoxy)benzamide (25) had a K-i = 0.565 nM for kappa opioid receptor binding while having a K-i = 35.8 nM for mu opioid receptors and a K-i = 211 nM for delta opioid receptor binding. Compound 25 was also a potent antagonist of K opioid receptors when tested in vitro using a [S-35]-guanosine 5'O-[3-thiotriphosphate] ([S-35]GTP-gamma-S) functional assay in CHO cells expressing cloned human opioid receptors. Compounds were also evaluated for potential use as receptor occupancy tracers. Tracer evaluation was done in vivo, using liquid chromatography-tandem mass spectrometry (LC/MS/MS) methods, precluding the need for radiolabeling. (S)-3-Chloro-4-(4-((2-(pyridine-3-yl(pyrrolidin-1-yl)methyl)phenoxy)benzamide (18) was found to have favorable properties for a tracer for receptor occupancy, including good specific versus nonspecific binding and good brain uptake.

  DOI：

  10.1021/jm200789r

文献信息

• [EN] DIARYL ETHERS AS OPIOID RECEPTOR ANTAGONIST<br/>[FR] DIARYLE ETHERS UTILISES EN TANT QU'ANTAGONISTES DE RECEPTEUR OPIOIDES
  申请人：LILLY CO ELI

  公开号：WO2004026305A1

  公开（公告）日：2004-04-01

  A compound of the formula (I) wherein the variables X1 to X10, R1 to R7 including R3', E, v, y, z, A and B are as described, or a pharmaceutically acceptable salt, solvate, enantiomer, racemate, diastereomer or mixtures thereof, useful for the treatment, prevention or amelioration of obesity and Related Diseases is disclosed.

  公式（I）的化合物，其中变量X1至X10，R1至R7包括R3'，E，v，y，z，A和B如所述，或其药用盐，溶剂化物，对映体，消旋体，非对映异构体或其混合物，用于治疗、预防或改善肥胖和相关疾病。
• Diaryl ethers as opioid receptor antagonist
  申请人：Blanco-Pillado Maria-Jesus

  公开号：US20060217372A1

  公开（公告）日：2006-09-28

  A compound of the formula (I) wherein the variables X 1 to X 10 , R 1 to R 7 including R 3′ , E, v, y, z, A and B are as described, or a pharmaceutically acceptable salt, solvate, enantiomer, racemate, diastereomer or mixtures thereof, useful for the treatment, prevention or amelioration of obesity and Related Diseases is disclosed.

  本发明公开了一种化合物（I）的公式，其中变量X1至X10，R1至R7包括R3'，E，v，y，z，A和B如所述，或其药学上可接受的盐，溶剂合物，对映体，外消旋体，非对映体异构体或其混合物，用于治疗、预防或缓解肥胖和相关疾病。
• DIARYL ETHERS AS OPIOID RECEPTOR ANTAGONISTS
  申请人：Blanco-Pillado Maria-Jesus

  公开号：US20080255152A1

  公开（公告）日：2008-10-16

  A compound of the formula (I) wherein the variables X 1 to X 10 , R 1 to R 7 including R 3′ , E, v, y, z, A and B are as described, or a pharmaceutically acceptable salt, solvate, enantiomer, racemate, diastereomer or mixtures thereof, useful for the treatment, prevention or amelioration of obesity and Related Diseases is disclosed.

  本发明揭示了一种式(I)的化合物，其中变量X1至X10，R1至R7包括R3′，E，v，y，z，A和B如所述，或其药学上可接受的盐，溶剂合物，对映体，外消旋体，非对映体异构体或其混合物，用于治疗、预防或改善肥胖和相关疾病。
• Diaryl ethers as opioid receptor antagonists
  申请人：Eli Lilly and Company

  公开号：US07531557B2

  公开（公告）日：2009-05-12

  Compound 6-(2-fluoro-4-[[2-(tetrahydro-pyran-4-yl)-ethylamino]-methyl]-phenoxy)-nicotinamide, or a pharmaceutically acceptable salt thereof, is useful for the treatment of alcoholism.

  6-(2-氟-4-[[2-(四氢吡喃-4-基)-乙基氨基]-甲基]-苯氧基)-烟酰胺化合物，或其药学上可接受的盐，可用于治疗酗酒症。
• Structure activity relationship studies of carboxamido-biaryl ethers as opioid receptor antagonists (OpRAs). Part 2
  作者：Kumiko Takeuchi、William G. Holloway、Charles H. Mitch、Steven J. Quimby、Jamie H. McKinzie、Todd M. Suter、Michael A. Statnick、Peggy L. Surface、Paul J. Emmerson、Elizabeth M. Thomas、Miles G. Siegel

  DOI：10.1016/j.bmcl.2007.10.025

  日期：2007.12

  A series of 6-bicycloaryloxynicotinamides were identified as opioid receptor antagonists at mu, kappa, and delta receptors. Compounds in the 6-(2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-yloxy)nicotinamide scaffold exhibited potent in vitro functional antagonism at all three receptors. (c) 2007 Elsevier Ltd. All rights reserved.