Patent Evaluation: Imidazotriazine TNF Inhibitors

Summary

Novelty: Imidazotriazines are disclosed which inhibit the production of IL-I and TNF. Accordingly they are potentially useful for the treatment of a number of inflammatory diseases in which these cytokines are involved.

Biology: Inhibition of IL-I or TNF production was demonstrated by incubating test compounds with lipopolysaccharide-stimulated peripheal blood monocytes for two days. Commercial ELISAs were used to quantify the cytokines. Data are given for three compounds, e.g. the compound shown had a IC₅₀ of 1.3 × 10⁻⁷M against IL-I production.

Chemistry: Eleven illustrative preparations of intermediate imidazotriazines, prepared from condensation of aminotriazines with acetophenones, are described; physical data are given for many more compounds. Twenty detailed synthetic examples are given, with a further seventy compounds prepared in analogous manner e.g. 6-(4-chlorophenyl)-7-(pyrid-4-yl)-1,2,3,4-tetrahydroimidazo[1,2-b][1,2,4]triazine. None is specifically claimed.