DESIGN AND SYNTHESIS OF A CONFORMATIONALLY RESTRICTED CYSTEINE PROTEASE INHIBITOR

被引:27
作者
CHENG, HM [1 ]
KEITZ, P [1 ]
JONES, JB [1 ]
机构
[1] UNIV TORONTO,DEPT CHEM,TORONTO,ON M5S 1A1,CANADA
关键词
D O I
10.1021/jo00104a022
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Using the X-ray analyses of papain and papain-chloromethyl ketone inhibitor complexes as representative cysteine protease structures, molecular graphics analyses were applied to design (4R,1'S)-2-[1'-[(benzyloxycarbon)amino]ethyl]4-benzyl-4-[[(2-oxoethyl)amino]carbonyl]-3,4,5,6-tetrahydropyrimidine (1) as a conformationally restricted, competitive inhibitor of cysteine proteases. Two routes to this target inhibitor, which was found to be a good competitive inhibitor of papain with a K-I of 790 nM, are described.
引用
收藏
页码:7671 / 7676
页数:6
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