N¹-(pyridin-2-yl)benzene-1,3-diamine

• 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: N¹-(pyridin-2-yl)benzene-1,3-diamine
• 英文别名: N1-(pyridin-2-yl)benzene-1,3-diamine；3-N-pyridin-2-ylbenzene-1,3-diamine
• 化学式: C₁₁H₁₁N₃
• 分子量: 185.228
• InChiKey: GQBOWXHZEYEJOF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  50.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N¹-(pyridin-2-yl)benzene-1,3-diamine 、 对氯苯异氰酸酯 以 氯仿 为溶剂， 以73%的产率得到N-(4-chlorophenyl)-N’-{3-[(pyridin-2-yl)amino]phenyl}urea
  参考文献：
  名称：

  PSNCBAM-1 analogs: Structural evolutions and allosteric properties at cannabinoid CB1 receptor

  摘要：

  Allosteric modulation of the CB1Rs could represent an alternative strategy for the treatment of diseases in which these receptors are involved, without the undesirable effects associated with their orthosteric stimulation. PSNCBAM-1 is a reference diaryl urea derivative that positively affects the binding affinity of orthosteric ligands (PAM) and negatively affects the functional activity of orthosteric ligands (NAM) at CB1Rs. In this work we reported the design, synthesis and biological evaluation of three different series of compounds, derived from structural modifications of PSNCBAM-1 and its analogs reported in the recent literature. Almost all the new compounds increased the percentage of binding affinity of CP55940 at CB1Rs, showing a PAM profile. When tested alone in the [ 35 S]GTPyS functional assay, only a few derivatives lacked detectable activity, so were tested in the same functional assay in the presence of CP55940. Among these, compounds 11 and 18 proved to be functional NAMs at CB1Rs, dampening the orthosteric agonist-induced receptor functionality by approximately 30%. The structural features presented in this work provide new CB1R-allosteric modulators (with a profile similar to the reference compound PSNCBAM-1) and an extension of the structure-activity relationships for this type of molecule at CB1Rs. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112606
• 作为产物：
  描述：

  2-溴吡啶 、 间苯二胺 在 potassium tert-butylate 作用下， 以 甲苯 为溶剂， 反应 48.0h， 以85%的产率得到N¹-(pyridin-2-yl)benzene-1,3-diamine
  参考文献：
  名称：

  PSNCBAM-1 analogs: Structural evolutions and allosteric properties at cannabinoid CB1 receptor

  摘要：

  Allosteric modulation of the CB1Rs could represent an alternative strategy for the treatment of diseases in which these receptors are involved, without the undesirable effects associated with their orthosteric stimulation. PSNCBAM-1 is a reference diaryl urea derivative that positively affects the binding affinity of orthosteric ligands (PAM) and negatively affects the functional activity of orthosteric ligands (NAM) at CB1Rs. In this work we reported the design, synthesis and biological evaluation of three different series of compounds, derived from structural modifications of PSNCBAM-1 and its analogs reported in the recent literature. Almost all the new compounds increased the percentage of binding affinity of CP55940 at CB1Rs, showing a PAM profile. When tested alone in the [ 35 S]GTPyS functional assay, only a few derivatives lacked detectable activity, so were tested in the same functional assay in the presence of CP55940. Among these, compounds 11 and 18 proved to be functional NAMs at CB1Rs, dampening the orthosteric agonist-induced receptor functionality by approximately 30%. The structural features presented in this work provide new CB1R-allosteric modulators (with a profile similar to the reference compound PSNCBAM-1) and an extension of the structure-activity relationships for this type of molecule at CB1Rs. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112606

文献信息

• [EN] 2, 4 -DIAMINOPYRIMIDINE DERIVATIVES AS PROTEIN KINASE INHIBITORS<br/>[FR] DÉRIVÉS DE 2,4-DIAMINOPYRIMIDINE EN TANT QU'INHIBITEURS DE PROTÉINE KINASES
  申请人：AURIGENE DISCOVERY TECH LTD

  公开号：WO2012059932A1

  公开（公告）日：2012-05-10

  The present invention relates to novel pyrimide derivatives of formula (I): that are useful as kinase inhibitors. More particularly, the present invention relates to novel pyrimidine compounds, methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of proliferative disorders.

  本发明涉及一种新型的式（I）的嘧啶衍生物，其作为激酶抑制剂具有用途。更具体地，本发明涉及新型嘧啶化合物、其制备方法、含有这些化合物的药物组合物以及这些化合物在治疗增殖性疾病中的用途。
• PSNCBAM-1 analogs: Structural evolutions and allosteric properties at cannabinoid CB1 receptor
  作者：Serena Meini、Francesca Gado、Lesley A. Stevenson、Maria Digiacomo、Alessandro Saba、Simone Codini、Marco Macchia、Roger G. Pertwee、Simone Bertini、Clementina Manera

  DOI：10.1016/j.ejmech.2020.112606

  日期：2020.10

  Allosteric modulation of the CB1Rs could represent an alternative strategy for the treatment of diseases in which these receptors are involved, without the undesirable effects associated with their orthosteric stimulation. PSNCBAM-1 is a reference diaryl urea derivative that positively affects the binding affinity of orthosteric ligands (PAM) and negatively affects the functional activity of orthosteric ligands (NAM) at CB1Rs. In this work we reported the design, synthesis and biological evaluation of three different series of compounds, derived from structural modifications of PSNCBAM-1 and its analogs reported in the recent literature. Almost all the new compounds increased the percentage of binding affinity of CP55940 at CB1Rs, showing a PAM profile. When tested alone in the [ 35 S]GTPyS functional assay, only a few derivatives lacked detectable activity, so were tested in the same functional assay in the presence of CP55940. Among these, compounds 11 and 18 proved to be functional NAMs at CB1Rs, dampening the orthosteric agonist-induced receptor functionality by approximately 30%. The structural features presented in this work provide new CB1R-allosteric modulators (with a profile similar to the reference compound PSNCBAM-1) and an extension of the structure-activity relationships for this type of molecule at CB1Rs. (C) 2020 Elsevier Masson SAS. All rights reserved.