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 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.
Refouvelet
B
B
Equipe de Chimie Thérapeutique, Faculté de Médecine et de Pharmacie, Besançon, France.
Harraga
S
S
Nicod
L
L
Robert
J F
JF
Seilles
E
E
Couquelet
J
J
Tronche
P
P
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
D000276:Adjuvants, Immunologic; D001643:Bridged Bicyclo Compounds; D015375:Receptors, Interleukin-2; D013141:Spiro Compounds; D007978:Levamisole