Synthesis and preliminary biological evaluation of novel N-substituted 1-amino-3[1-methyl(phenyl)-1H-indazol-4-yloxy]-propan-2-ols interesting as potential antiarrhythmic, local anaesthetic and analgesic agents

A series of indazoloxypropanolamines 7 and 8, pindolol isosteres, were synt hezised to extend the structure activity relationship (SAR) which was obser ved in an earlier series of related derivatives. Compounds 7, characterized by methyl substitution on the N-1 indazole nucleus, generally exhibited si gnificant antiarrhythmic, local anaesthetic and analgesic activities. The p reliminary radioligand binding assay highlighted, in compounds 7, an intere sting Pi-affinity which can be well correlated to their antiarrhyhtmic acti vity. Analogues 8 characterized by a phenyl group on the N-1 indazole nucle us, were generally less active as antiarrhyhtmic agents but generally inter esting as local anaesthetics. Due to the importance of the indazole moiety as a carrier of antiphlogistic activity, the two classes of derivatives 7 a nd 8 were evaluated for their NSAID behaviour. Once again, compounds 7 resu lted having more interesting analgesic and antipyretic effects than analogu es 8.