N-(6-bromopyridin-2-yl)-4-propoxybenzamide | 1447423-77-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(6-bromopyridin-2-yl)-4-propoxybenzamide
• CAS: 1447423-77-9
• 化学式: C₁₅H₁₅BrN₂O₂
• 分子量: 335.2
• InChiKey: JWXAGDZHVUFGEL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  正己胺 、 N-(6-bromopyridin-2-yl)-4-propoxybenzamide 在 tris-(dibenzylideneacetone)dipalladium(0) 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 甲苯 为溶剂， 以64%的产率得到N-(6-(hexylamino)pyridin-2-yl)-4-propoxybenzamide
  参考文献：
  名称：

  Discovery of benzamide analogs as negative allosteric modulators of human neuronal nicotinic receptors: Pharmacophore modeling and structure–activity relationship studies

  摘要：

  The present study describes our ongoing efforts toward the discovery of drugs that selectively target nAChR subtypes. We exploited knowledge on nAChR ligands and their binding site that were previously identified by our laboratory through virtual screenings and identified benzamide analogs as a novel chemical class of neuronal nicotinic receptor (nAChR) ligands. The lead molecule, compound 1 (4-(allyloxy)-N-(6-methylpyridin-2-yl)benzamide) inhibits nAChR activity with an IC50 value of 6.0 (3.4-10.6) mu M on human alpha 4 beta 2 nAChRs with a similar to 5-fold preference against human alpha 3 beta 4 nAChRs. Twenty-six analogs of compound 1 were also either synthesized or purchased for structure-activity relationship (SAR) studies and provided information relating the chemical/structural properties of the molecules to their ability to inhibit nAChR activity. The discovery of subtype-selective ligands of nAChRs described here should contribute significantly to our understanding of the involvement of specific nAChR subtypes in normal and pathophysiological states. (C) 2013 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2013.03.082
• 作为产物：
  描述：

  2-氨基-6-溴吡啶 、 4-丙氧基苯甲酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以81%的产率得到N-(6-bromopyridin-2-yl)-4-propoxybenzamide
  参考文献：
  名称：

  Discovery of benzamide analogs as negative allosteric modulators of human neuronal nicotinic receptors: Pharmacophore modeling and structure–activity relationship studies

  摘要：

  The present study describes our ongoing efforts toward the discovery of drugs that selectively target nAChR subtypes. We exploited knowledge on nAChR ligands and their binding site that were previously identified by our laboratory through virtual screenings and identified benzamide analogs as a novel chemical class of neuronal nicotinic receptor (nAChR) ligands. The lead molecule, compound 1 (4-(allyloxy)-N-(6-methylpyridin-2-yl)benzamide) inhibits nAChR activity with an IC50 value of 6.0 (3.4-10.6) mu M on human alpha 4 beta 2 nAChRs with a similar to 5-fold preference against human alpha 3 beta 4 nAChRs. Twenty-six analogs of compound 1 were also either synthesized or purchased for structure-activity relationship (SAR) studies and provided information relating the chemical/structural properties of the molecules to their ability to inhibit nAChR activity. The discovery of subtype-selective ligands of nAChRs described here should contribute significantly to our understanding of the involvement of specific nAChR subtypes in normal and pathophysiological states. (C) 2013 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2013.03.082

文献信息

• Discovery of benzamide analogs as negative allosteric modulators of human neuronal nicotinic receptors: Pharmacophore modeling and structure–activity relationship studies
  作者：Bitna Yi、Sihui Long、Tatiana F. González-Cestari、Brandon J. Henderson、Ryan E. Pavlovicz、Karl Werbovetz、Chenglong Li、Dennis B. McKay

  DOI：10.1016/j.bmc.2013.03.082

  日期：2013.8

  The present study describes our ongoing efforts toward the discovery of drugs that selectively target nAChR subtypes. We exploited knowledge on nAChR ligands and their binding site that were previously identified by our laboratory through virtual screenings and identified benzamide analogs as a novel chemical class of neuronal nicotinic receptor (nAChR) ligands. The lead molecule, compound 1 (4-(allyloxy)-N-(6-methylpyridin-2-yl)benzamide) inhibits nAChR activity with an IC50 value of 6.0 (3.4-10.6) mu M on human alpha 4 beta 2 nAChRs with a similar to 5-fold preference against human alpha 3 beta 4 nAChRs. Twenty-six analogs of compound 1 were also either synthesized or purchased for structure-activity relationship (SAR) studies and provided information relating the chemical/structural properties of the molecules to their ability to inhibit nAChR activity. The discovery of subtype-selective ligands of nAChRs described here should contribute significantly to our understanding of the involvement of specific nAChR subtypes in normal and pathophysiological states. (C) 2013 Published by Elsevier Ltd.