文章基本信息

标题：Structure-Activity Relationships of Alkylxanthine Inhibitors of Phosphodiesterase IV Isoenzyme
本地全文：下载
作者：Kenji YAMAMOTO ; Hiroyuki SAWANISHI ; Ken-ichi MIYAMOTO 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1998
卷号：21
期号：4
页码：356-359
DOI：10.1248/bpb.21.356
出版社：The Pharmaceutical Society of Japan
摘要：The structural and electronic properties of seventeen alkylxanthine derivatives were calculated using the MO program PM3 to elucidate the key features related to their inhibitory activity on phosphodiesterase (PDE) IV isoenzyme. Except for 7-alkylxanthine derivatives, a good correlation could be established between the distance between the tops of the two alkyl groups at the N¹ and N³ positions of the xanthine skeleton (molecular length) and the PDE IV inhibitory activity (r=0.973, n=13). The same inhibitory activity could also be significantly correlated with the following electronic parameters of alkylxanthines : HOMO energy (r=0.850), absolute hardness (r=-0.806), and absolute electronegativity (r=-0.825). These results suggest that the electronic properties are partly responsible for PDE IV inhibition as far as the effects of structural properties associated with molecular length are concerned. Alkylxanthines may also act as electron donors in the charge-transfer interaction with the active sites on PDE IV isoenzyme.
关键词：alkylxanthine;PDE IV inhibition;structure-activity relationship;MO calclulation;HOMO energy