Substituted 6,7-dihydroimidazo[1,2-a]purin-9(4H)-ones

Abstract

The synthesis of a series of substituted 6,7-dihydroimidazo[1,2-a]purin-9(4H)-ones is described. Several members of the series exhibit enhanced antiallergic and bronchodilator activity and reduced side effects as compared to theophylline. Structure-activity relationships and metabolic considerations are discussed for the series. Analogues substituted with a 4-(4-chlorobenzyl) moiety, such as 33 and 40, shown an optimal balance of antiallergic and bronchodilator activity and are of particular interest. Compound 33 is significantly more potent than theophylline against both metacholine- and antigen-induced bronchospasms, does not affect spontaneous motor activity, and shows minimal cardiovascular effects in the rat.

Synthesis and anticonvulsant activity of some substituted lactams and amides

“…All compounds in Table I were evaluated as anticonvulsants in mice via the Anticonvulant Screening Project, which is conducted by the Epilepsy Branch of the National Institute of Neurological and Communicative Disorders and Stroke. The screening procedure has been described in detail by Krall et al4 5 Briefly, candidate compounds were initially subjected to a preliminary screen in a small number of mice (1)(2)(3)(4) at dose levels of 30, 100, and 300 mg/kg. The smallest dose that produced activity was noted for separate tests involving subcutaneous Metrazol-induced convulsions (scMet), maximal electroshockinduced convulsions (MES), and a rotorod toxicity test.…”

Antiallergics: 3-(1H-tetrazol-5-yl)-4H-pyrimido[2,1-b]benzothiazol-4-ones

“…We have previously reported a series of thieno [2,3-d]pyrimidine-5-carboxylic acid derivatives as orally active mediator release inhibitors having no bronchodilator component.6 Subsequently, we have described 4-substituted imidazo[l,2-o]purin-9-ones as bronchodilators having greater potency and fewer side-effect liabilities than theophylline in animal models. 7 Members of this series also show significant antiallergic activity.…”

Synthetic Strategies for Preparing Bicyclic Guanidines

“…[40] An alternative cyclisation strategy based on a substituted 2-aminobenzimidazole intermediate and diethyl malonate was described by Esser [41] and Di Braccio. [40] An alternative cyclisation strategy based on a substituted 2-aminobenzimidazole intermediate and diethyl malonate was described by Esser [41] and Di Braccio.…”