NOVEL ANTIASTHMATIC AGENTS WITH DUAL ACTIVITIES OF THROMBOXANE A(2) SYNTHETASE INHIBITION AND BRONCHODILATION .1. 2-[2-(1-IMIDAZOLYL)ALKYL]-1(2H)-PHTHALAZINONES

A number of 4-substituted -[omega-(1-imidazolyl)allryl]-1(2H)-phthalaz inones were synthesized in order to develop agents possessing both thr omboxane Az synthetase inhibitory and bronchodilatory activities. The pharmacological evaluation of these compounds disclosed that they have both activities to various extents. Both activities were slightly dep endent on the length of the 2-substituents and largely affected by the nature of the 4-substituents. Compounds bearing phenyl and thienyl gr oups exhibited relatively high and well-rounded activities. Among thes e compounds, 12j and 15f were found to be the most effective agents ha ving well-rounded activities in vitro and in vivo. Introduction of a c arboxyl group reduced both activities contrary to our expectation. 4-( 3-Pyridyl)phthalazinone 18b was of particular interest because of unex pectedly high in vivo activities in spite of an absence of significant in vitro activities.