NOVEL COMPOUNDS POSSESSING POTENT CAMP AND CGMP PHOSPHODIESTERASE INHIBITORY ACTIVITY - SYNTHESIS AND CARDIOVASCULAR EFFECTS OF A SERIES OF IMIDAZO[1,2-A]QUINOXALINONES AND IMIDAZO[1,5-A]QUINOXALINONES AND THEIR AZA ANALOGS

被引:46
作者
DAVEY, DD [1 ]
ERHARDT, PW [1 ]
CANTOR, EH [1 ]
GREENBERG, SS [1 ]
INGEBRETSEN, WR [1 ]
WIGGINS, J [1 ]
机构
[1] BERLEX LABS INC,DEPT PHARMACOL,CEDAR KNOLLS,NJ 07927
关键词
D O I
10.1021/jm00113a002
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A series of novel imidazoquinoxalinones and their aza analogues were prepared by the cyclization of o-amino(H-1-imidazol-1-yl)aryls and heteroaryls with carbonyldiimidazole. The compounds were screened for inhibition of Type I and Type IV phosphodiesterases (PDE's) and evaluated for their vasorelaxant and positive inotropic activities in vitro. In general, compounds having potent PDE inhibitory activity also possessed good inotropic and vasodilator activity, although linear correlations between these activities could not be established.
引用
收藏
页码:2671 / 2677
页数:7
相关论文
共 25 条
[1]  
ABRAMS J, 1989, DRUG THER, P109
[2]  
AHLNER J, 1987, ARZNEIMITTEL-FORSCH, V37-2, P914
[3]   EFFECT OF INVITRO ORGANIC NITRATE TOLERANCE ON RELAXATION, CYCLIC-GMP ACCUMULATION, AND GUANYLATE-CYCLASE ACTIVATION BY GLYCERYL TRINITRATE AND THE ENANTIOMERS OF ISOIDIDE DINITRATE [J].
BENNETT, BM ;
SCHRODER, H ;
HAYWARD, LD ;
WALDMAN, SA ;
MURAD, F .
CIRCULATION RESEARCH, 1988, 63 (04) :693-701
[4]  
BRIEN JF, 1986, J PHARMACOL EXP THER, V237, P608
[5]  
CARGNELLI C, 1989, J CARDIOVASC PHAR S8, V14, pS124
[6]   NITRATES ARE EFFECTIVE IN THE TREATMENT OF CHRONIC CONGESTIVE HEART-FAILURE - THE PROTAGONISTS VIEW [J].
COHN, JN .
AMERICAN JOURNAL OF CARDIOLOGY, 1990, 66 (04) :444-446
[7]   CARDIOTONIC AGENTS .1. NOVEL 8-ARYL-SUBSTITUTED IMIDAZO[1,2-A] AND [1,5-A]PYRIDINES AND IMIDAZO[1,5-A]PYRIDINONES AS POTENTIAL POSITIVE INOTROPIC AGENTS [J].
DAVEY, D ;
ERHARDT, PW ;
LUMMA, WC ;
WIGGINS, J ;
SULLIVAN, M ;
PANG, D ;
CANTOR, E .
JOURNAL OF MEDICINAL CHEMISTRY, 1987, 30 (08) :1337-1342
[9]   IN SEARCH OF THE DIGITALIS REPLACEMENT [J].
ERHARDT, PW .
JOURNAL OF MEDICINAL CHEMISTRY, 1987, 30 (02) :231-237
[10]  
GALLOWAY MP, 1983, J PHARMACOL EXP THER, V227, P1