Pyrazolothiazolopyrimidine derivatives as a novel class of anti-inflammatory or antinociceptive agents: synthesis, structural characterization and pharmacological evaluation

Article abstract of DOI:10.1016/0223-5234(93)90123-V

As a part of a research program on anti-inflammatory-analgesic compounds, pyrazolothiazolopyrimidines 5a-f and 5g-i were prepared by cyclodehydration in 98percent H2SO4 or PPA of the corresponding 6-thioketomethylene-substituted-4-hydroxypyrazolo<3,4-d>pyrimidinies 2a-i and 2g-i.The results of the pharmacological in vivo screening indicate an interesting dissociation of the analgesic from the anti-inflammatory activity depending on aromatic or aliphatic substitution at C4 of the thiazole ring.Analgesic activity was not associated with any narcotic affect: in addition, all th e active compounds showed a remarkable systemic and gastric tolerance.This indicated a mode of action different from that of the classical nonsteroidal anti-inflammatory drugs, acting on prostaglandin biosynthesis.To clarify the mechanism or the mechanisms underlying the pharmacological activity of these and other closely related compounds, we initiated a 'file chemical approach' to various systems involved in the inflammatory process.At present, some of the more active in vivo compounds tested as substance P antagonists showed a moderate and possibly non-specific effect on NK1 and NK2 receptors. pyrazolothiazolopyrimidine derivatives / anti-inflammatory-analgesic activity / substance P antagonists