New derivatives of 5 H-pyridazino (4,5- b) indole and 1,2,4-triazino (4,5- a) indole and related compounds as inhibitors of blood platelet aggregation, anti-hypertensive agents and thromboxane synthetase inhibitors

Abstract

This paper reports the synthesis of a series of hydrazone 2, tetrazole 3, triazole 4, pyrrole 5, 8, pyrazole 6, 9, 12 and 1,2,4-triazino[4,5- a]indole 10 derivatives, obtained from 4-hydrazino-8-methoxy-5 H-pyridazino[4,5- b]indole 1a, 4-hydrazino-8,9-dimethoxy-5 H-pyridazino[4,5- b]indole 1b, 5-methoxy- and 5,6-dimethoxyindole-2-carbohydrazides 7 and 4-hydrazino-7-methoxy-1,2,4-triazino[4,5- a]indole 11. All these new products and some other related compounds, previously reported by the authors, were studied as inhibitors of platelet aggregation in whole guinea pig blood, induced by arachidonic acid (AA), adenosine-5′-diphosphate (ADP) or collagen. Some of the most active anti-aggregating compounds were also studied as anti-hypertensive agents in spontaneously hypertensive rats (SHR) and as inhibitors of thromboxane synthetase. Acute toxicities in mice were also determined for the most interesting compounds.