公开(公告)号：KR1020010077073A

公开(公告)日：2001-08-17

申请号：KR1020000004631

申请日：2000-01-31

Applicant: 한국과학기술연구원

Inventor： 조정혁 ,  오창현 ,  김희권

IPC: C07D473/16

Abstract: PURPOSE: Provided are novel adenine compounds which inhibit the cyclin dependent kinase (CDK), specifically, isopropylpurine derivatives with the substitution at C-2,6,9 positions and their preparation method. These adenine compounds are more effective than existing olomousine and roscovitine in CDK inhibition. CONSTITUTION: The compounds are represented by chemical formula 1, wherein R1 is piperidino, piperazino, pyrrolidino or thiomorpholino group which is substituted by one or more groups selected from hydroxyalkyl amino, hydroxy, hydroxyalkyl, carboxylic acid, aldehyde and oxim group. Most preferably R1 is hydroxyalkylamino or 4-carboxy-2-hydroxymethyl pyrrolidino group. The preparation process includes the steps of: reacting 2,6-dichloropurine with 3-chloroaniline in butanol solution; reacting the resultant compound with isopropyl halide in the presence of strong base and reacting the product, in 4:1 mixed solvent of n-butanol and DMSO, with piperidine, piperazino, pyrrolidino or thiomorpholino group which is substituted by one or more group selected from hydroxyalkyl amino, hydroxy, hydroxyalkyl, carboxylic acid, aldehyde and oxim group.

Abstract translation: 目的：提供抑制细胞周期蛋白依赖性激酶（CDK）的新型腺嘌呤化合物，特别是C-2,6,9位取代的异丙基嘌呤衍生物及其制备方法。 这些腺嘌呤化合物在CDK抑制中比现有的olomousine和roscovitine更有效。 构成：化合物由化学式1表示，其中R 1是被一个或多个选自羟基烷基氨基，羟基，羟基烷基，羧酸，醛和肟基的基团取代的哌啶子基，哌嗪子基，吡咯烷子基或硫代吗啉代基团。 最优选R 1是羟烷基氨基或4-羧基-2-羟甲基吡咯烷子基。 制备方法包括以下步骤：使2,6-二氯嘌呤与3-氯苯胺在丁醇溶液中反应; 使所得化合物与异丙基卤化物在强碱存在下反应，并使产物在正丁醇和DMSO的4:1混合溶剂中与哌啶，哌嗪子基，吡咯烷子基或硫代吗啉代基反应，所述哌啶，哌嗪基，吡咯烷子基或硫代吗啉代基被一个或多个选自 羟基烷基氨基，羟基，羟烷基，羧酸，醛和肟基。