INHIBITORS OF HUMAN RENIN - CYCLIC PEPTIDE ANALOGS CONTAINING A D-PHE-LYS-D-TRP SEQUENCE

被引:5
作者
DUTTA, AS [1 ]
GORMLEY, JJ [1 ]
MCLACHLAN, PF [1 ]
MAJOR, JS [1 ]
机构
[1] ICI PLC,DEPT BIOSCI,MACCLESFIELD SK10 4TG,CHESHIRE,ENGLAND
关键词
D O I
10.1021/jm00171a034
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Cyclic peptides containing a D-phenylalanine and a D-tryptophan residue have been synthesized and tested as inhibitors of human renin. Most of these are tripeptide derivatives of the type CO(CH2)3CO-D-Phe-Lys-D-Trp- or COCH2NHCH2CO-D-Phe-Lys-D-Trp- in which the individual side-chain methylene groups have been replaced with -CHMe- -CMe2-, -CH{Ph)-, -CH(CH2Ph)- or -CH((CH2)2CHMe2)-groups. The three amino acid residues and the size of the ring were very important features of these compounds. Reducing the ring size gave much less potent compounds. The most potent analogue of the series, CO(CH2)2CHPhCO-D-Phe-Lys-D-Trp-NH(CH2)2CHMe2(14, ICso = 26 nM), was obtained by substituting the methylene group nearer to the D-Phe residue by a -CHPh- group. Compound 14 was 15-fold more potent in inhibiting human renin than porcine renin. © 1990, American Chemical Society. All rights reserved.
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页码:2560 / 2568
页数:9
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