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A series of tricyclic, highly water-soluble theophylline derivatives (pyrimido[2,1-f]-theophyllines) containing a basic side chain was investigated in rat brain A1- and A2 adenosine receptor binding assays, phosphodiesterase assays, and benzodiazepine binding studies. Among the new compounds adenosine receptor antagonists with affinities in the same range as the parent compound theophylline were identified. In addition, some compounds were selective for the A1 adenosine receptor subtype. The compounds generally exhibited lower inhibitory activity at brain phosphodiesterases than the parent theophylline. Two compounds were found to show an about 10-fold affinity for benzodiazepine binding sites compared with caffeine and theophylline.

Two series of N10 substituted derivatives of 1,3-dimethyl-2,4,9-trioxo-1,3,6,7,8,10-hexahydro-1,3-diazepino+ ++-[2,1-f]- purine and 1,3-dimethyl-2,4-dioxo-1,3,6,7,8,9-hexahydro-10H-1,3-dizepino- [2,1-f]-purine were synthesized and tested for CNS activity. The most active in central nervous system tests were compounds [II] and [XIV].

In a search for new compounds with cardiovascular activity several derivatives of 8-benzylaminotheophylline with hydroxyalkyl and hydroxyalkylamino substituents at 7-position have been obtained. Some of these compounds were screened for their hypotensive activity.

In order to examine the circulatory and bronchospasmolytic activity, new 7-beta-hydroxy-gamma-N4-alkylpiperazinopropyl-8- benzylaminotheophyllines (1, 2, 3) were synthesized and converted to the water soluble dihydrochlorides (1a, 2a, 3a). They showed hypotensive and bronchodilatory effect.

The synthetic routes leading to 7-beta-hydroxyethyl- (I) and 7-beta-hydroxypropyl-8-benzylaminotheophylline (II) were described. Particularly the opening of oxazolidine ring in easy available oxazolidine-(2,3-f)-theophyllines with benzylamine was investigated. The structure of I, II and acetyl derivatives Ia, Ib, IIa and IIb was also confirmed by UV spectra.