Synthesis and immunological activity of 5,6,6a,8,9,11a-hexahydronaphth[1',2':4,5]imidazo[2,1-b]thiazoles and 5,6,6a,9,10,11a-hexahydroanaphth[2',1':4,5]imidazo[2,1-b]thiazoles.
A series of 5,6,6a,8,9,11a-hexahydroanaphth[1',2':4,5]imidazo[2,q-b]thiazoles (17 and 20) and 5,6,6a,9,10,11a-hexahydronaphth[2',1':4,5]imidazo[2,1-b]thiazoles has been synthesized with cis- and/or trans-1,2-diamino-1,2,3,4-tetrahydronaphthalenes as the key intermediates and subsequently evaluated for immunological activity (effects on antibody formation and delayed-type hypersensitivity reaction). Among the compounds tested trans-5,6,6a,8,9,11a-hexahydronaphth[1',2':4,5]imidazo[2,1-b]thiazole (trans-17a) and (+/-)-5,6,6a beta,8,9,11a alpha-hexahydro-8 beta-hydroxy-9 beta-methyl-8 alpha-phenylnaphth[1',2':4,5]imidazo[2,1-b]thiazole (20a) showed the largest immunological activity in mice with a magnitude comparable to that of levamisole and were found to be considerably less toxic than levamisole in acute toxicological study. The structures of 18a and 20a were determined by X-ray crystallography.
D000276:Adjuvants, Immunologic / Q000138:chemical synthesis*; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D006462:Hemolytic Plaque Technique; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology; D007928:Lethal Dose 50; D051379:Mice; D012756:Sheep / Q000276:immunology; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D007093:Imidazoles; D013844:Thiazoles