Archiv der Pharmazie p. 689 - 698 (1995)
Update date:2022-08-05
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Martinez-Irujo
This paper presents the synthesis of new indole, pyridazino[4,5-b]-indole, and pyridazino[4,5-a]indole analogs were 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]acetamidopyri dazino[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.
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