一些具有支气管扩张活性的新型黄嘌呤类衍生物的鉴定。

Identification of some novel xanthine-based derivatives with bronchodilator activity.

作者信息

Mohamed Abdalla R, Georgey Hanan H, George Riham F, El-Eraky Wafaa I, Saleh Dalia O, Abdel Gawad Nagwa M

机构信息

Pharmaceutical Chemistry Department, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt.

Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.

出版信息

Future Med Chem. 2017 Oct;9(15):1731-1747. doi: 10.4155/fmc-2017-0092. Epub 2017 Sep 5.

DOI:10.4155/fmc-2017-0092

PMID:28871831

Abstract

AIM

The discovery of new bronchodilators with higher efficacy than theophylline is an important issue for asthmatic patients.

MATERIALS & METHODS: Theophylline 2, 8-bromotheophylline 4 and theobromine 6 were reacted with different 2/3-chloro-N-phenylacetamides 1a-d or their propanamide analogs 1e-g to obtain 3a-g, 5a-g and 7a-g, respectively. The target compounds were screened for their in vitro bronchodilator activity using isolated guinea pig tracheal rings precontracted with histamine and compared with their precursors.

RESULTS

Many compounds exhibited promising activity especially 3d, 3f, 5d, 7d and 7e. 2D-QSAR study resulted in a significant model (N = 24, n = 5, R = 0.848, R cvOO = 0.748, R cvMO = 0.745, F = 21.215, s = 0.0002) using CODESSA-Pro software.

CONCLUSION

These compounds can be considered as promising hits for potent bronchodilators that may be useful for further investigations. [Formula: see text].

摘要

目的

发现比茶碱疗效更高的新型支气管扩张剂对哮喘患者而言是一个重要课题。

材料与方法

使茶碱2、8-溴茶碱4和可可碱6分别与不同的2/3-氯-N-苯基乙酰胺1a-d或其丙酰胺类似物1e-g反应，分别得到3a-g、5a-g和7a-g。使用组胺预收缩的豚鼠离体气管环对目标化合物进行体外支气管扩张活性筛选，并与它们的前体进行比较。

结果

许多化合物表现出有前景的活性，尤其是3d、3f、5d、7d和7e。使用CODESSA-Pro软件进行的二维定量构效关系（2D-QSAR）研究得出了一个显著模型（N = 24，n = 5，R = 0.848，R cvOO = 0.748，R cvMO = 0.745，F = 21.215，s = 0.0002）。