Antibacterial agents pyridazines

In West Germany pyridazinium compounds as represented by formula (120, R1 = halogen, alkyl, aryl R2 = H, alkyl R3 = substituted amino R4 = substituted alkyl, cycloalkyl) have been claimed as antibacterial agents [338]. In Australia, mercapto derivatives of several nitrogen heteroaromatics including pyridazine-derived compounds (121, R = CONH2, CH2NMe2) have been prepared in a search of amplifiers of phleomycin [339] however, only low activity has been observed in this series. 

In search of novel and more effective antibacterial agents, numerous /1-lactam antibiotics bearing a pyridazine core have been synthesized mainly in Japan. Thus, the penicillin derivative (125) characterized by a 3-hydroxypyridazine-4-carboxamido subunit has been patented as a broad-spectrum bactericide [342-345] likewise, the corresponding cephalosporin analogue has been claimed in a patent [346]. 

Kidwai and Kumar ° reported a microwave-accelerated reaction of urea 232 with phenacylbromide to yield the iminooxazoline 233 (Scheme 1.64). In this case, the total reaction time required was only 1.0-1.5 min. Patel and Fernandes prepared the 2-amino-4-substituted oxazoles 235 as precursors to novel oxa-zolo[5,4-c]pyrazoles and oxazolo[5,4-c]pyridazines, which were evaluated as antibacterial agents. Cyclization of a-bromoketones 234 with urea in refluxing DMF afforded 235 (Scheme 1.65). 

In 1977, a review on the antimicrobial activity of pyridazine derivatives was published [309]. Accordingly, in the present article, antibacterial pyridazines developed more than a decade ago will be mentioned only briefly. Synonyms of the agents (95)-(104) listed below are given in areference book [96]. In order... 

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