MERCAPTOACYL AMINO-ACID INHIBITORS OF ATRIOPEPTIDASE .1. STRUCTURE-ACTIVITY RELATIONSHIP STUDIES OF METHIONINE AND S-ALKYLCYSTEINE DERIVATIVES

被引：11

作者：

NEUSTADT, BR ^{[1
]}

SMITH, EM ^{[1
]}

NECHUTA, TL ^{[1
]}

BRONNENKANT, AA ^{[1
]}

HASLANGER, MF ^{[1
]}

WATKINS, RW ^{[1
]}

FOSTER, CJ ^{[1
]}

SYBERTZ, EJ ^{[1
]}

机构：

[1] SCHERING PLOUGH CORP,RES INST,DEPT PHARMACOL,KENILWORTH,NJ 07033

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1994年 / 37卷 / 15期

关键词：

D O I：

10.1021/jm00041a026

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A broad series of N-(3-mercaptoacyl) amino acid derivatives was evaluated for their ability to inhibit atriopeptidase (neutral endopeptidase, EC 3.4.24.11) in vitro and in vivo. Structural parameters studied were (i) the substituent on the 2-position of the 3-mercaptopropionyl moiety, (ii) the amino acid component, (iii) the S-terminal derivative, and (iv) the C-terminal derivative. Optimum activity was observed for derivatives of methionine and S-alkylcysteines. N-[3-Mercapto-2(S)-[(2-methylphenyl)methyl]-1-oxopropyl]-L-methionine was identified as a highly effective inhibitor of atriopeptidase meriting evaluation as a potential cardiovascular therapeutic agent.

引用

页码：2461 / 2476

页数：16

共 48 条

[1]

ALTSTEIN M, 1982, EUR J PHARMACOL, V76, P299

[2] ANTIHYPERTENSIVE ACTIVITY OF SCH-31846, A NON-SULFHYDRYL ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR [J].

BAUM, T ;

SYBERTZ, EJ ;

WATKINS, RW ;

AHN, HS ;

NELSON, S ;

EYNON, E ;

VANDERVLIET, G ;

PULA, KK ;

SABIN, C ;

DESIDERIO, DM ;

BECKER, FT ;

VEMULAPALLI, S .

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1983, 5 (04) :655-667

[3] RELATIONSHIP BETWEEN THE INHIBITORY POTENCIES OF THIORPHAN AND RETROTHIORPHAN ENANTIOMERS ON THERMOLYSIN AND NEUTRAL ENDOPEPTIDASE-24.11 AND THEIR INTERACTIONS WITH THE THERMOLYSIN ACTIVE-SITE BY COMPUTER MODELING [J].

BENCHETRIT, T ;

FOURNIEZALUSKI, MC ;

ROQUES, BP .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1987, 147 (03) :1034-1040

[4]

Bindra J. S., 1982, U.S. Patent, Patent No. [4,329,495, 4329495]

[5]

BODANSZKY M, 1966, PEPTIDE SYNTHESIS, P142

[6] BIDENTATE PEPTIDES - HIGHLY POTENT NEW INHIBITORS OF ENKEPHALIN DEGRADING ENZYMES [J].

BOUBOUTOU, R ;

WAKSMAN, G ;

DEVIN, J ;

FOURNIEZALUSKI, MC ;

ROQUES, BP .

LIFE SCIENCES, 1984, 35 (09) :1023-1030

[7]

BROWN H, 1959, Patent No. 2888380

[8]

CHIPKIN RE, 1988, J PHARMACOL EXP THER, V245, P829

[9] BIOACTIVE CARDIAC SUBSTANCES - POTENT VASORELAXANT ACTIVITY IN MAMMALIAN ATRIA [J].

CURRIE, MG ;

GELLER, DM ;

COLE, BR ;

BOYLAN, JG ;

WU, YS ;

HOLMBERG, SW ;

NEEDLEMAN, P .

SCIENCE, 1983, 221 (4605) :71-73

[10] SPECTROPHOTOMETRIC ASSAY AND PROPERTIES OF ANGIOTENSIN-CONVERTING ENZYME OF RABBIT LUNG [J].

CUSHMAN, DW ;

CHEUNG, HS .

BIOCHEMICAL PHARMACOLOGY, 1971, 20 (07) :1637-+

← 1 2 3 4 5 →