N-cyclohexyl-7-methyl-1-benzyl-1,8-naphthyridin-4(1H)-one-3-carboxamide | 700364-68-7

• 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: N-cyclohexyl-7-methyl-1-benzyl-1,8-naphthyridin-4(1H)-one-3-carboxamide
• 英文别名: N-cyclohexyl-7-methyl-1-benzyl-1,8-naphthyridin-4(1H)-on-3-carboxamide；1-benzyl-N-cyclohexyl-7-methyl-4-oxo-1,8-naphthyridine-3-carboxamide
• CAS: 700364-68-7
• 化学式: C₂₃H₂₅N₃O₂
• 分子量: 375.47
• InChiKey: YMSSGAXHTVJMPD-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：
  0.35
• 拓扑面积：
  62.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-cyclohexyl-7-methyl-1-benzyl-1,8-naphthyridin-4(1H)-one-3-carboxamide 在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 12.0h， 以52%的产率得到1-Benzyl-4-hydroxy-7-methyl-1,2,3,4-tetrahydro-[1,8]naphthyridine-3-carboxylic acid cyclohexylamide
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of New 1,8-Naphthyridin-4(1H)-on-3-carboxamide and Quinolin-4(1H)-on-3-carboxamide Derivatives as CB₂ Selective Agonists

  摘要：

  On the basis of docking studies carried out using the recently published cannabinoid receptor models,(35) new 1,8-naphthyridin-4(1H)-on-3-carboxamide and quinolin-4(1H)-on-3-carboxamide derivatives were designed, synthesized, and tested for their affinities toward the cannabinoid CB1 and CB2 receptors. Compound 10, which presented p-fluorobenzyl and carboxycycloheptylamide substituents bound in the 1 and 3 positions of the 1,8-naphthyiridine-4-one nucleus, showed a high CB2 affinity with a K-i of 1.0 nM. The substitution of the naphthyridine-4-one nucleus with the quinoline-4-one system determined a general increase in CB2 affinity. In particular, the N-cyclohexyl-7-chloro-1-(2-morpholin-4-ylethyl) quinolin-4(1H)-on-3-carboxamide (40) possessed a remarkable affinity, with K-i of 3.3 nM, which was also accompanied by a high selectivity for the CB2 receptor (K-i(CB1)/K-i(CB2) ratio greater than 303). Moreover, the [S-35]GTP gamma binding assay and functional studies on human basophils indicated that the 1,8-naphthyridin-4(1H)-on-3-carboxamide derivatives behaved as CB1 and CB2 receptor agonists.

  DOI：

  10.1021/jm0603466
• 作为产物：
  描述：

  7-甲基-4-氧代-3H-1,8-萘啶-3-羧酸乙酯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 N-cyclohexyl-7-methyl-1-benzyl-1,8-naphthyridin-4(1H)-one-3-carboxamide
  参考文献：
  名称：

  作为大麻素受体新配体的1,8-萘啶-4（1H）-on-3-羧酰胺衍生物的合成和生物学评估。

  摘要：

  鉴于大麻​​受体在几种生理和病理过程中的潜在功能作用，已经对其进行了广泛的研究。因此，为了研究其在各种生理功能中的作用，寻找亚型CB受体CB（1）和CB（2）的新的有效，选择性配体仍然非常重要。本研究描述了一系列1,8-萘啶衍生物的合成和生物学特性，其特征是存在其他类别的大麻素配体（例如3位的脂肪族或芳香族羧酰胺基团）表现出的一些重要结构要求，以及在位置1处的烷基或芳基烷基取代基。分析了这些化合物与大脑和外围大麻素受体（CB（1）和CB（2））的结合。获得的结果表明，所检查的萘啶衍生物对CB（2）受体的亲和力大于对CB（1）受体的亲和力。尤其是，衍生物6a和7a对CB（2）受体具有明显的亲和力，K（i）值分别为5.5和8.0 nM。化合物4a，5a和8a也表现出良好的CB（2）亲和力，K（i）值在10-44 nM的范围内。此外，化合物3g-i和18显示出良好的CB（2）选择性，CB（1）/

  DOI：

  10.1016/j.bmc.2004.01.035

文献信息

• Synthesis and biological evaluation of 1,8-naphthyridin-4(1H)-on-3-carboxamide derivatives as new ligands of cannabinoid receptors
  作者：Pier Luigi Ferrarini、Vincenzo Calderone、Tiziana Cavallini、Clementina Manera、Giuseppe Saccomanni、Luca Pani、Stefania Ruiu、Gian Luigi Gessa

  DOI：10.1016/j.bmc.2004.01.035

  日期：2004.4

  affinity for the CB(2) receptor than for the CB(1) receptor. In particular, derivatives 6a and 7a possess an appreciable affinity for the CB(2) receptor, with K(i) values of 5.5 and 8.0 nM respectively; also compounds 4a, 5a and 8a exhibit a good CB(2) affinity, with K(i) values in the range of 10-44 nM. Furthermore, compounds 3g-i and 18 revealed a good CB(2) selectivity, with a CB(1)/CB(2) ratio >20.

  鉴于大麻​​受体在几种生理和病理过程中的潜在功能作用，已经对其进行了广泛的研究。因此，为了研究其在各种生理功能中的作用，寻找亚型CB受体CB（1）和CB（2）的新的有效，选择性配体仍然非常重要。本研究描述了一系列1,8-萘啶衍生物的合成和生物学特性，其特征是存在其他类别的大麻素配体（例如3位的脂肪族或芳香族羧酰胺基团）表现出的一些重要结构要求，以及在位置1处的烷基或芳基烷基取代基。分析了这些化合物与大脑和外围大麻素受体（CB（1）和CB（2））的结合。获得的结果表明，所检查的萘啶衍生物对CB（2）受体的亲和力大于对CB（1）受体的亲和力。尤其是，衍生物6a和7a对CB（2）受体具有明显的亲和力，K（i）值分别为5.5和8.0 nM。化合物4a，5a和8a也表现出良好的CB（2）亲和力，K（i）值在10-44 nM的范围内。此外，化合物3g-i和18显示出良好的CB（2）选择性，CB（1）/
• Design, Synthesis, and Biological Evaluation of New 1,8-Naphthyridin-4(1<i>H</i>)-on-3-carboxamide and Quinolin-4(1<i>H</i>)-on-3-carboxamide Derivatives as CB₂ Selective Agonists
  作者：Clementina Manera、Veronica Benetti、M. Paola Castelli、Tiziana Cavallini、Sara Lazzarotti、Fabio Pibiri、Giuseppe Saccomanni、Tiziano Tuccinardi、Alfredo Vannacci、Adriano Martinelli、Pier Luigi Ferrarini

  DOI：10.1021/jm0603466

  日期：2006.10.1

  On the basis of docking studies carried out using the recently published cannabinoid receptor models,(35) new 1,8-naphthyridin-4(1H)-on-3-carboxamide and quinolin-4(1H)-on-3-carboxamide derivatives were designed, synthesized, and tested for their affinities toward the cannabinoid CB1 and CB2 receptors. Compound 10, which presented p-fluorobenzyl and carboxycycloheptylamide substituents bound in the 1 and 3 positions of the 1,8-naphthyiridine-4-one nucleus, showed a high CB2 affinity with a K-i of 1.0 nM. The substitution of the naphthyridine-4-one nucleus with the quinoline-4-one system determined a general increase in CB2 affinity. In particular, the N-cyclohexyl-7-chloro-1-(2-morpholin-4-ylethyl) quinolin-4(1H)-on-3-carboxamide (40) possessed a remarkable affinity, with K-i of 3.3 nM, which was also accompanied by a high selectivity for the CB2 receptor (K-i(CB1)/K-i(CB2) ratio greater than 303). Moreover, the [S-35]GTP gamma binding assay and functional studies on human basophils indicated that the 1,8-naphthyridin-4(1H)-on-3-carboxamide derivatives behaved as CB1 and CB2 receptor agonists.