Synthesis, anti-inflammatory and ulcerogenicity studies of some substituted pyrimido[1,6-a]azepine derivatives.

New series of pyrimido[1,6-a]azepines were prepared through reaction of the key amino compound 4 with various reagents to give a variety of 3-N-substituted amino derivatives 5-13. The synthesized compounds included the Mannich bases 5a-c, the formimidic acid ester 6, the phenylformamidines 7a-c, the benzylidine amino derivatives 8a-c, the acetic acid derivatives 9, 10a-c and 11, the carbamoylformates 12a,b and the amides 13a,b. All compounds were screened for their anti-inflammatory activity using the carrageenan-induced paw oedema in rats using diclofenac sodium as reference drug. In addition, ulcer indices for the most active compounds were calculated. Compounds 3, 4, 8a,c, 11 and 12a,b showed activity similar to or higher than diclofenac sodium with no or minimal gastric ulceration. The most active compound with no ulcerogenic effect is the amino derivative 4 (IC 50 = 6.61 mmol/kg).