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European Journal of Pharmaceutical Sciences 11 (2000) 285–290 www.elsevier.nl/locate/ejps Synthesis and pharmacological evaluation of novel heterotricyclic acylhydrazone derivatives, designed as PAF antagonists Aline G.M. Fraga, Carlos R. Rodrigues, Ana L.P. de Miranda, Eliezer J. Barreiro, Carlos A.M. Fraga* ´ ˜ ´ ˆ ´ Laboratorio de Avaliac¸ao e Sıntese de Substancias Bioativas (LASSBio, http:// www.ufrj.br / pharma / lassbio), Faculdade de Farmacia, Universidade Federal do Rio de Janeiro, P.O. Box 68006, 21944 -970, Rio de Janeiro, RJ, Brazil Received 25 November 1999; received in revised form 26 April 2000; accepted 27 April 2000 Abstract This paper describes the synthesis and the antiplatelet properties of new heterotricyclic N -acylhydrazone derivatives (7a–e), structurally analogous to known hetrazepinic PAF antagonists, exploring molecular hybridization as a tool for molecular designing. The synthetic route employed to access compounds (7a–e) used, as starting material, the previously described methyl 3-hydroxy-8-methyl-6-phenyl-6H - pyrazolo[3,4-b]thieno[2,3-d]pyridine-2-carboxylate derivative. The results from inhibitory effects of these novel acylhydrazone deriva- tives (7a–e) upon PAF-induced platelet aggregation, indicated that all compoun