发现8-羟基腺嘌呤作为一种新型干扰素诱导剂。

Discovery of 8-hydroxyadenines as a novel type of interferon inducer.

作者信息

Hirota Kosaku, Kazaoka Kazunori, Niimoto Itaru, Kumihara Hiroshi, Sajiki Hironao, Isobe Yoshiaki, Takaku Haruo, Tobe Masanori, Ogita Haruhisa, Ogino Tetsuhiro, Ichii Shinji, Kurimoto Ayumu, Kawakami Hajime

机构信息

Laboratory of Medicinal Chemistry, Gifu Pharmaceutical University, Mitahora-higashi, Gifu 502-8585, Japan.

出版信息

J Med Chem. 2002 Dec 5;45(25):5419-22. doi: 10.1021/jm0203581.

DOI:10.1021/jm0203581

PMID:12459008

Abstract

9-Benzyl-8-hydroxyadenine (6) was found to possess interferon-inducing activity in vitro as a lead compound. Although replacement of the 9-benzyl group of 6 did not improve the activity, the introduction of a substituent such as alkyl, alkylthio, alkylamino, and alkoxy groups into the 2-position of the adenine ring resulted in a remarkable increase in the activity. The 2-alkylthio (30-32), 2-butylamino (41), and 2-butoxy (47) analogues indicated the highest activities by oral administration to mice.

摘要

9-苄基-8-羟基腺嘌呤（6）作为先导化合物，在体外被发现具有诱导干扰素的活性。尽管6的9-苄基被取代后活性并未提高，但在腺嘌呤环的2-位引入诸如烷基、烷硫基、烷氨基和烷氧基等取代基会导致活性显著增加。2-烷硫基（30 - 32）、2-丁氨基（41）和2-丁氧基（47）类似物经口服给予小鼠后显示出最高活性。