SULFAMATE ANTICONVULSANTS: STUCTURE AND FUNCTION.

P.W. Codding, S.A. Litster, M. Kubicki, M.B. Szkaradzinska, and H.A.R. Bassyouini, Departments of Chemistry and Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, Canada, T2N 1N4.

Studies of novel sulfamate anticonvulsant drugs developed by E.B. Maryanoff1 show that activity correlates with a skew conformation of the central ring and an extended conformation of the sulfonamide side chain. Additionally, the crystal structures of active compounds demonstrate unique hydrogen bonding networks. Clinical trials of compound 1 (topiramate) it is effective against partial-onset seizures. We have determined the crystal structures of six related compounds; conformational, graph set and modeling analysis of these data will be presented. Compound 1: (topiramate) 2,3:4,5-bis-O-(1-methylethylidene)-b-D-fructopyranose sulfamate, Compound 2: 4,5-O-cyclohexylidene-2,3-O-(1-methylethylidene)-6-D-fructopyranose sulfamate, Compound 3: 2,3-O-(1-methylethylidene)-b-D-fructopyranose sulfamate, Compound 4: 1,2:3,4-bis-O-(1-methylethylidene)-a-D-galactopyranose sulfamate, Compound 5: 1,2,3,4,-Tetrahydro-2-naphthalenyl methyl sulfamic acid ester, Compound 6: 1,4 benzodioxin-2-(3H) methyl; sulfamic acid ester.

1 E.B. Maryanoff, The R.W. Johnson Pharmaceutical Research Institute.