IMMUNOMODULATORY AGENTS - DIOXOTHIADIAZABICYCLO [3.3.0]OCTANES AND THEIR 2-SPIRO DERIVATIVES

A series of 6,8-dioxo-3-thia-1,7-diazabicyclo[3.3.0]octanes and a seri es of 6,8-dioxo-3-thia-1,7-diazabicyclo[3.3.0]octane 2-spiro derivativ es were synthesized from L-(-)-R-cysteine ethyl ester in two steps. Th e synthetic route involved condensation of the amino acid with an appr opriate aldehyde or ketone, then a further condensation of the resulta nt ethyl thiazolidine-4-carboxylate with an isocyanate or an isothiocy anate. The proliferative response to human lymphocyte mitogen (phytohe magglutinin) was used as a primary screening assay for most of the thi adiazabicyclic compounds in comparison with levamisole. Furthermore, t he most active compounds were tested for ability to release soluble re ceptors (sRIL-2) after mitogenic stimulation of T cells and for abilit y to activate macrophage oxidative metabolism measured by chemilumines cence. Most compounds were active in all three tests and some showed d ose-dependent activity.