Synthesis and biological evaluation of novel laropiprant derivatives as potential anti-allergic agents

被引：3

作者：

Zhou, Haiping ^{[1
]}

Zhu, Qihua ^{[1
]}

Gan, Zongjie ^{[2
]}

Dong, Guangping ^{[2
]}

Xu, Yungen ^{[1
,2
]}

机构：

[1] China Pharmaceut Univ, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Jiangsu, Peoples R China

[2] China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Jiangsu, Peoples R China

来源：

MEDICINAL CHEMISTRY RESEARCH | 2015年 / 24卷 / 11期

关键词：

Anti-allergic agents; Laropiprant derivatives; Synthesis; Flushing; Biological evaluation; D-2 RECEPTOR ANTAGONIST; PROSTAGLANDIN D-2; NICOTINIC-ACID; DP RECEPTOR; NIACIN; INFLAMMATION; MK-0524; ASTHMA;

D O I：

10.1007/s00044-015-1431-8

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

DP antagonists are claimed to be useful in the treatment of allergic disorders. Laropiprant is a potent and selective DP antagonist to reduce the allergic disorders, especially niacin-induced flushing. In our study, a series of novel laropiprant derivatives (I-1-I-18) were synthesized and characterized by IR, H-1-NMR, C-13-NMR and HRMS spectrum. The potency of these compounds was evaluated in a murine model of niacin-induced flushing. The results indicated that most compounds exhibited faster-acting effect of suppressing vasodilation than laropiprant. Among them, I-1, I-2, I-3, I-9, I-13, I-15 and I-16 exhibited substantial flushing inhibitory effect. Especially, I-1 and I-2 showed higher potency than laropiprant and would be valuable for further investigation.

引用

页码：3920 / 3931

页数：12