1-(4-cyanophenyl)-3-(4-(dimethylamino)phenyl)urea

• 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: 1-(4-cyanophenyl)-3-(4-(dimethylamino)phenyl)urea
• 英文别名: LDK1320；1-(4-Cyanophenyl)-3-[4-(dimethylamino)phenyl]urea；1-(4-cyanophenyl)-3-[4-(dimethylamino)phenyl]urea
• 化学式: C₁₆H₁₆N₄O
• 分子量: 280.329
• InChiKey: INYKDEVTWDJGBN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  68.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-氰基苯异氰酸酯 、 N,N-二甲基-对苯二胺 以 二氯甲烷 为溶剂， 反应 2.17h， 以87.5%的产率得到1-(4-cyanophenyl)-3-(4-(dimethylamino)phenyl)urea
  参考文献：
  名称：

  Structural Optimization of the Diarylurea PSNCBAM-1, an Allosteric Modulator of Cannabinoid Receptor 1

  摘要：

  Background: Structure-activity relationship studies improve the pharmacological and pharmacokinetic properties of a lead compound such as PSNCBAM-1, an allosteric modulator of the cannabinoid receptor 1. Objectives: Here, several derivatives of PSNCBAM-1 were synthesized with the aim of reducing the number of rings within its structure and enhancing the solubility of the compounds. The derivatives studied contain substituents previously shown to enhance binding of agonists (ie, a cyano group and a pyrimidine ring), with a reduced number of rings compared with the parent compound, PSNCBAM-1.Methods: The synthesized compounds were tested for the enhancement of the binding of orthosteric cannabinoid receptor 1 agonist CP55,940 in the presence of varying concentrations of each test compound. Select compounds were also tested for their effects on cannabinoid receptor 1 inverse agonist SR141716A binding. The compounds were also subjected to computational analysis of drug-like properties and solubility.Results: Consistent with a positive allosteric modulator for orthosteric ligand binding, compounds LDK1317 (12a), LDK1320 (12b), LDK1321 (6a), LDK1323 (8a), and LDK1324 (6b) all enhanced the binding of agonist CP55,940 to some degree. Reduction in the number of rings did not abolish the activity. The new lead compounds LDK1317 (12a) and LDK1321 (6a) showed improved drug-like properties and enhanced solubility in silico.Conclusions: In contrast to PSNCBAM-1, the synthesized compounds are analogs with fewer rings. The compounds LDK1317 (12a) and LDK1321 (6a) contained only 2 or 3 rings, respectively, and showed the binding parameters (K-B = 110 nM, alpha = 2.3, and K-B = 85 nM, alpha = 5.9). Further, the computationally predicted drug-like properties and solubility suggest these compounds are acceptable new lead compounds for further development of cannabinoid receptor 1 allosteric modulators. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX) (c) 2019 The Author(s). Published by Elsevier Inc.

  DOI：

  10.1016/j.curtheres.2019.100574