Abstract
New types of bronchodilator agents, bi- and tricyclic nitrogen bridgehead compounds with a pyrimidin-4(3H)-one ring, were synthesized and evaluated for bronchodilator activity against serotonin-, histamine-, and acetylcholine-induced spasms in the guinea pig Konzett-Rössler test. The structure-activity relationships are discussed. The effects of some bi- and tricyclic derivatives on the human bronchus were also investigated. The homologous tricyclic compounds 68 and 69 were tested on isolated guinea pig ileum and trachea, and the effects of compound 69 were investigated in pilocarpine-treated dogs. Azepino[2,1-b]quinazoline (69; CHINOIN-1289) was selected for further biochemical and clinical investigations.
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