乙内酰脲衍生物RU58841的合成工艺研究  

A New Method for Synthetic Methods of Hydantoin Derivative RU58841

作　　者：王晓霞 曹碧霞 杨欣梓 李泽坤 刘荣 WANG Xiao-xia;CAO Bi-xia;YANG Xin-zi;LI Ze-kun;LIU Rong(Gansu Chemical Industry Research Institute Co.,Ltd.,Lanzhou 730020,China;Key Laboratory of Fine Chemicals,Gansu Province,Lanzhou 730020,China;Department of Chemistry,Norhwest Minzu University,Lanzhou 730030,China)

机构地区：[1]甘肃省化工研究院有限责任公司,甘肃兰州730020 [2]甘肃省精细化工重点实验室,甘肃兰州730020 [3]西北民族大学化工学院,甘肃兰州730030

出　　处：《化学试剂》2022年第9期1398-1402,共5页Chemical Reagents

基　　金：甘肃省科技计划项目——重点研发计划项目(20YF3WA001)。

摘　　要：乙内酰脲(IUPAC:咪唑烷-2,4-二酮)核是一种具有广泛的生物和药理活性且具有4个功能点的五元杂环药理骨架。这种小而刚性的骨架可以有效地作用于各种药理靶点,几种临床上重要的药物如苯妥英(抗癫痫药)、阿齐利特(抗心律失常药)和尼鲁米特(抗雄激素药)等都是基于这种特征性的主要骨架。RU58841(IUPAC名称:4-[3-(4-羟基丁基)-4,4-二甲基-2,5-二氧咪唑啉-1-基]-2-(三氟甲基)苯甲腈)是一种具有抗秃发活性的乙内酰脲衍生物,研究表明RU58841几乎没有毒性,有望成为一种新的外用非甾体抗雄激素。研究发现以4-氨基-2-(三氟甲基)苄腈为原料,通过三光气制备异氰酸酯、[3+2]环加成、N-烷基化和脱保护共4步反应制备RU58841,总收率为40%。与传统方法相比,该方法可以更方便、更安全地获得RU58841。Hydantoinis(IUPAC:Imidazolidine-2,4-dione),a five-membered heterocyclic compound with four functional points,show various amazing biological and pharmacological activity.This small and rigid backbone could effectively act on various pharmacological targets.Several clinically important medicines such as phenytoin(antiepileptic),azimilide(antiarrhythmic)and nilutamide(antiandrogen)are based upon this characteristic staple scaffold.RU58841(IUPAC name:4-[3-(4-hydroxybutyl)-4,4-dimethyl-2,5-dioxoimidazolidin-1-yl]-2-(trifluoromethyl)benz onitrile)was found active against baldness with little evidence of toxicity,and it has promise as a new topically active non-steroidal antiandrogen.We reported a new alternative synthesis of RU58841.RU58841 was synthesized using 4-amino-2-(trifluoromethyl)benzonitrile as raw material in 4 steps including the preparation of isocyanate,[3+2]cycloaddition,N-alkylation and deprotection with over-all yield of 40%.Compare to traditional method,the method can be more convenient and safer to get RU58841.

关 键 词：三光气 乙内酰脲 RU58841 [3+2]环加成 抗秃发剂 

分 类 号：O62[理学—有机化学]