title: Immunomodulatory agents: dioxothiadiazabicyclo[3.3.0]octanes and their 2-spiro derivatives.
abstract: A series of 6,8-dioxo-3-thia-1,7-diazabicyclo[3.3.0]octanes and a series of 6,8-dioxo-3-thia-1,7-diazabicyclo[3.3.0]octane 2-spiro derivatives were synthesized from L-(-)-R-cysteine ethyl ester in two steps. The synthetic route involved condensation of the amino acid with an appropriate aldehyde or ketone, then a further condensation of the resultant ethyl thiazolidine-4-carboxylate with an isocyanate or an isothiocyanate. The proliferative response to human lymphocyte mitogen (phytohemagglutinin) was used as a primary screening assay for most of the thiadiazabicyclic compounds in comparison with levamisole. Furthermore, the most active compounds were tested for ability to release soluble receptors (sRIL-2) after mitogenic stimulation of T cells and for ability to activate macrophage oxidative metabolism measured by chemiluminescence. Most compounds were active in all three tests and some showed dose-dependent activity.
authors.affiliation: Equipe de Chimie Thérapeutique, Faculté de Médecine et de Pharmacie, Besançon, France.
authors.forename: B
authors.initials: B
authors.lastname: Refouvelet
authors.forename: S
authors.initials: S
authors.lastname: Harraga
authors.forename: L
authors.initials: L
authors.lastname: Nicod
authors.forename: J F
authors.initials: JF
authors.lastname: Robert
authors.forename: E
authors.initials: E
authors.lastname: Seilles
authors.forename: J
authors.initials: J
authors.lastname: Couquelet
authors.forename: P
authors.initials: P
authors.lastname: Tronche
mesh_terms: D000276:Adjuvants, Immunologic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002478:Cells, Cultured; D006801:Humans; D007978:Levamisole / Q000494:pharmacology; D008163:Luminescent Measurements; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D010084:Oxidation-Reduction; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D001643:Bridged Bicyclo Compounds; D015375:Receptors, Interleukin-2; D013141:Spiro Compounds; D007978:Levamisole