Transformations of naproxen into pyrazolecarboxamides: search for potent anti-inflammatory, analgesic and ulcerogenic agents

Abstract

Many derivatives of naproxen containing a variety of pyrazolecarboxamides were synthesized through the reaction of naproxenoyl hydrazide with formylpyrazole, acetylacetone, enaminone, Mannich base, and arylhydrazonomalononitrile derivatives. Also, many derivatives of naproxen were synthesized through the reaction of naprexenoyl chloride with amine derivatives containing pyrazole moiety. The synthesized compounds were screened for anti-inflammatory, analgesic, and ulcerogenic activities. Screening of anti-inflammatory revealed that compound 5 having a 1,3-diphenyl-pyrazol-4-yl moiety had the most promising activity. Compounds 8, 9, and 12, possessing 3,5-dimethyl-pyrazol-1-yl, 3-phenyl-pyrazol-1-yl, and 3,5-diamino-4-(4-methoxyphenylazo)-pyrazol-1-yl groups, respectively, showed moderate activity. Moreover, compounds 8 and 12 showed higher analgesic activity than the reference drug. In ulcerogenic effect, compound 22 which has methoxphenyl pyrazoline moiety devoid of ulcerogenic effect.