Studies on the Syntheses of N-Heterocyclic Compounds. XXV.1) Syntheses of Pyrido[3,4-d]pyridazine Derivatives. (2)

Abstract

Investigations on the preparative methods and some chemical modifications of the previously reported potent diuretic, 1,4-dimorpholino-7-phenylpyrido[3,4-d|pyridazine (1: DS-511) were undertaken, producing a variety of derivatives shown in Table I. Comparison of the reactivity between the two chloro groups in 1,4-dichloropyrido[3,4-d]pyridazine showed that the 4-chloro group is more reactive toward nucleophilic substitution than the 1-chloro group. Some reaction of 1, e.g. acid hydrolysis, reduction and Grignard addition reaction were also carried out. Significance of the ring nitrogen at the 6-position in 1 for diuretic activity is discussed. © 1975, The Pharmaceutical Society of Japan. All rights reserved.