SYNTHESIS AND INHIBITORY ACTIVITIES AGAINST AMINOPEPTIDASE-B AND ENKEPHALIN-DEGRADING ENZYMES OF KETOMETHYLENE DIPEPTIDE ANALOGS OF ARPHAMENINES

被引：0

作者：

GARCIALOPEZ, T ^{[1
]}

GONZALEZMUNIZ, R ^{[1
]}

HARTOA, JR ^{[1
]}

GOMEZMONTERREY, I ^{[1
]}

PEREZ, C ^{[1
]}

DECEBALLOS, ML ^{[1
]}

LOPEZ, E ^{[1
]}

DELRIO, J ^{[1
]}

机构：

[1] CSIC,INST CAJAL,E-28002 MADRID,SPAIN

来源：

ARCHIV DER PHARMAZIE | 1992年 / 325卷 / 01期

关键词：

D O I：

暂无

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Three ketomethylene pseudodipeptide analogues [(S)Lys-PSI(COCH2)(R and S)Phe (14 or 15 and 15 or 14) and (S)Lys-PSI(COCH2)(xi-TrP (19)] of natural arphamenine A [(S)Arg-PSI(COCH2(R,S)Phe (1)] were easily prepared by a route involving two successive main reactions: a malonic ester alkylation with Z-protected lysine iodomethyl ketone and the introduction of a benzyl or (indol-3-yl)methyl moiety in position 2 of the resulting 4-ketodiester. The isomer of 1 with reversed sequence, (S)Phe-PSI(COCH2)(RS)Arg (22) was synthesized by guanidylation and subsequent deprotection of Z-(S)Phe-PSI(COCH2)(R,S)Orn. The inhibitory effects of compounds 14, 15, 19, and 22, and the related ketomethylene dipeptides (S)Ala-PSI(COCH2)(R,S)Phe (3), (S)Phe-PSI(COCH2)(R,S)X [X = Ala (4), Orn (5)] (S)Trp-PSI(COCH2) (R,S)Y [Y = Orn (6), Lys (7), Arg (8)] on aminopeptidase B (AP-B), and enkephalin-degrading enzymes [aminopeptidase N (APN) and neutral endopeptidase (NEP)] were compared with that of the model compound 1.

引用

页码：3 / 8

页数：6