N-(4-methylcyclohexyl)-7-amino-1,8-naphthyridin-4(1H)-one-3-carboxamide | 913533-99-0

• 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-(4-methylcyclohexyl)-7-amino-1,8-naphthyridin-4(1H)-one-3-carboxamide
• 英文别名: 7-amino-N-(4-methylcyclohexyl)-4-oxo-1H-1,8-naphthyridine-3-carboxamide
• CAS: 913533-99-0
• 化学式: C₁₆H₂₀N₄O₂
• 分子量: 300.36
• InChiKey: HIVLNQISPKNUQI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  97.1
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(4-methylcyclohexyl)-7-amino-1,8-naphthyridin-4(1H)-one-3-carboxamide 在 盐酸 、 sodium nitrite 作用下， 反应 3.0h， 以31%的产率得到N-(4-methylcyclohexyl)-7-chloro-1,8-naphthyridin-4(1H)-one-3-carboxamide
  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：

  1-氨基-4-甲基环己烷 、 ethyl-7-acetylamino-4-hydroxy-1,8-naphthyridine-3-carboxylate 反应 24.0h， 以83%的产率得到N-(4-methylcyclohexyl)-7-amino-1,8-naphthyridin-4(1H)-one-3-carboxamide
  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

文献信息

• 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.