Synthesis of New Heterocyclic Steroids as a Novel Class of Potent Anti-Inflammatory, Anti-Nociceptive and Anti­ Ulcerogenic Agents

Abstract

The identification of compounds able to treat both pain and inflammation with limited side effects is one of the prominent goals in biomedical research. This study aimed at the synthesis of new steroidal heterocyclic derivatives with structures justifying anti-inflammatory and anti-nociceptive activities. The steroidal heterocyclic derivatives were synthesized VIa straightforward and efficient methods and their structures were established based on the analytical and spectral data. The in vivo anti-inflammatory, anti-nociceptive and anti-ulcerogenic activities of some of these compounds were studied. The novel synthesized derivatives 8b, 19b, 24, 31a, 37, and 41a showed anti-inflammatory, antinociception and anti-ulcerogenic activity with various intensities. Oedema was significantly reduced by both doses (25 and 50 mg/kg) of • all tested compounds at 3 and 4h post-carrageenan. Compounds 19b, 37 and 46a were most effective in alleviating thermal pain. The analgesic activity of either dose of the compounds 8b, 24, 31a as well as the high dose 19b was significantly higher than indomethacin (IND). Gastric mucosal lesions caused in the rat by the administration of96% EtOH and IND were inhibited by all tested compounds administered at (50 mg/kg) dose in the study.