Synthesis and biological evaluation of 2,8-disubstituted 9-benzyladenines: Discovery of 8-mercaptoadenines as potent interferon-inducers
Synthesis and biological evaluation of 2,8-disubstituted 9-benzyladenines: Discovery of 8-mercaptoadenines as potent interferon-inducers
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DOI：
10.1016/s0968-0896(03)00234-7
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发表时间：
2003-07-03
影响因子：
3.5
通讯作者：
Sajiki, H
中科院分区：
文献类型：
--
作者：
Hirota, K;Kazaoka, K;Sajiki, H
最近，我们已经确定了9-苄基-8-羟基腺嘌呤轴承适当的取代基（丁氧基，丙硫基或丁氨基）在2位作为有效的干扰素（IFN）诱导剂。在此，我们报告的设计，合成，和干扰素诱导活性的8-取代的9-苄基腺嘌呤具有这样一个适当的取代基在2-位。在腺嘌呤核的2位引入适当的取代基，即使在8位不含羟基的9-苄基腺嘌呤中也能表达活性。需要在6-位的氨基和在8-位的携带酸性质子的羟基或巯基来表达优异的IFN-诱导活性。9-苄基-2-丁氧基-8-巯基腺嘌呤（9）显示最有效的活性，MEC为0.001 μ M。(C)2003爱思唯尔科技有限公司版权所有。
Recently, we have identified 9-benzyl-8-hydroxyadenines bearing an appropriate substituent (a butoxy, propylthio or butylamino group) at the 2-position as potent interferon (IFN)-inducers. Herein we report the design, synthesis, and IFN-inducing activity of 8-substituted 9-benzyladenines possessing such an appropriate substituent at the 2-position. Introduction of the appropriate substituent into the 2-position of the adenine nucleus gave rise to expression of the activity even in 9-benzyladenines bearing no hydroxyl group at the 8-position. An amino group at the 6-position and a hydroxyl or thiol group carrying an acidic proton at the 8-position are required to express excellent IFN-inducing activity. 9-Benzyl-2-butoxy-8-mercaptoadenine (9) indicated the most potent activity with MEC of 0.001 muM. (C) 2003 Elsevier Science Ltd. All rights reserved.