Synthesis and Muscle Relaxant Activity of Two Analogues of Dantrolene Sodium in Mice

Abstract

Dantrolene sodium (1) is a skeletal muscle relaxant that is known to act by preventing the release of calcium ions from the sarcoplasmic reticulum. Structure–activity studies of 1 have been limited to changes in the position or the nature of the nitro group, and replacement of the 4-nitrobenzene, furan, and hydantoin moieties with other rings, usually resulting in compounds with reduced or no activity. To investigate the influence of similarities in the electronic transmission ability of the furan nucleus of 5-aryl, 5-arylthio and 5-styryl-2-furancarboxaldehydes on biological activity, two corresponding analogues of 1 were prepared by the reaction of the respective aldehydes with 1-aminohydantoin and were evaluated by the rota-rod test in mice. Compared with 1 as standard, 1-[[[[5-(4-nitrobenzene)thio]-2-furanyl]-methylene] amino]-2,4-imidazolidinedione (2) exhibited higher activity, and 1-[[[[5-(4-nitrobenzene) ethenyl]-2-furanyl]-methylene]amino]-2,4-imidazolidinedione (3) showed comparable activity at 0.5, 3 and 6h after administration to mice. There is a correlation between the electronic transmission ability of the furan nucleus in compounds 1, 2 and 3 and muscle relaxant activity.