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New Indole and Pyridazinoindole Analogs — Synthesis and Study as Inhibitors of Phosphodiesterases and as Inhibitors of Blood Platelet Aggregation
Author(s) -
Monge Antonio,
Navarro MaríaEugenia,
Font María,
Santiago Esteban,
Alberdi Elena,
MartínezIrujo JuanJosé
Publication year - 1995
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19953281002
Subject(s) - indole test , chemistry , phosphodiesterase , stereochemistry , platelet , arachidonic acid , in vitro , biological activity , platelet aggregation , biochemistry , pharmacology , enzyme , biology , immunology
This paper presents the synthesis of new indole, pyridazino[4,5‐ b ]indole, and pyridazino[4,5‐ a ]indole analogs as well as a study of their “ in vitro ” activity as inhibitors of different phosphodiesterases isolated from dog cardiac tissue, dog aorta, and bovine platelets; the study of their activity as inhibitors of platelet aggregation in guinea pig whole blood, with ADP and arachidonic acid (AA) as pro‐aggregants, is also included. The selected compounds 8‐benzyloxy‐3,4‐dihydro‐1‐(3,4,5‐trimethoxy)benzylideneaminopyridazino[4,5‐ b ]indole 14g , and 8‐benzyloxy‐4‐[(3,5‐dimethyl)pyrazolyl]pyridazino[4,5‐ b ]indole 20 present an interesting profile as potential inodilators, with a complementary, beneficial activity as inhibitors of the aggregation, activities which could possibly be related to the inhibition of the PDE's. Among the other compounds studied, 8‐benzyloxy‐3,4‐dihydro‐1‐[4‐(methyl)piperazino]acetamidopyridazino[4,5‐ b ]indol‐4‐one 16c and 8‐benzyloxy‐3,4‐dihydro‐1‐[4‐(2‐methoxyphenyl)piperazino]acetamidopyridazino[4,5‐ b ]indol‐4‐one 16f stood out as inhibitors of platelet aggregation, with a mechanism that could possibly be related to the AA cascade.