Anticonvulsant derivatives useful in treating autism
AssigneeOrtho-McNeil Pharmaceutical, Inc.
InventorDaniel P. Van Kammen
Life of this patent
Estimating the term…
Abstract
Anticonvulsant derivatives useful in treating autism.
Drawings
Claims4
A method for treating an individual exhibiting one or more of the symptoms of autism in mammals comprising administering to such a mammal a therapeutically effective amount for treating such condition of a compound of Formula I:
wherein
X is CH2 or oxygen;
R1 is hydrogen or alkyl;
and
R2, R3, R4 and R5 are independently hydrogen or alkyl and, when X is CH2, R4 and R5, may be alkene groups joined to form a benzene ring and, when X is oxygen, R2 and R3 and/or R4 and R5 together may be a methylenedioxy group of the following formula(II):
wherein
R6 and R7 are the same or different and are hydrogen, or alkyl and are joined to form a cyclopentyl or cyclohexyl ring.
09/484,522Filed 18 Jan 2000 · us provisional application
Priority
8 Feb 1999
Published
US 2002/0035068 A121 Mar 2002
Granted
22 Apr 2003
Term ended
18 Jan 2020Estimated · howhide20 years from earliest known nonprovisional domestic filing. Maintenance-fee lapses, terminal disclaimers and statutory extensions have not been checked. The continuity chain may be incomplete; this is not an enforceability determination. Patent term adjustment is unavailable; no adjustment was added.
#are structurally novel antiepileptic compounds that are highly effective anticonvulsants in animal tests (Maryanoff, B. E, Nortey, S. O., Gardocki, J. F., Shank, R. P. and Dodgson, S. P. J. Med. Chem. 30, 880-887, 1987; Maryanoff, B. E., Costanzo, M. J., Shank, R. P., Schupsky, J. J., Ortegon, M. E., and Vaught J. L. Bioorganic & Medicinal Chemistry Letters 3, 2653-2656, 1993). These compounds are covered by U.S. Pat. No.4,513,006. One of these compounds 2,3:4,5-bis-O-(1-methylethylidene)-β-D-fructopyranose sulfamate known as topiramate has been demonstrated in clinical trials of human epilepsy to be effective as adjunctive therapy or as monotherapy in treating simple and complex partial seizures and secondarily generalized seizures (E. FAUGHT, B. J. WILDER, R. E. RAMSEY, R. A. REIFE, L D. KRAMER, G. W. PLEDGER, R. M. KARIM et. al., Epilepsia 36 (S4) 33, 1995; S. K. SACHDEO, R. C. SACHDEO, R. A. REIFE, P. LIM and G. PLEDGER, Epilepsia 36 (S4) 33, 1995), and is currently marketed for the treatment of simple and complex partial seizure epilepsy with or without secondary generalized seizures in approximately twenty countries including the United States, and applications for regulatory approval are presently pending in several additional countries throughout the world.
#Compounds of Formula I were initially found to possess anticonvulsant activity in the traditional maximal electroshock seizure (MES) test in mice (SHANK, R. P., GARDOCKI, J. F., VAUGHT, J. L., DAVIS, C. B., SCHUPSKY, J. J., RAFFA, R. B., DODGSON, S. J., NORTEY, S. O., and MARYANOFF, B. E., Epilepsia 35 450-460, 1994). Subsequent studies revealed that Compounds of Formula I were also highly effective in the MES test in rats. More recently topiramate was found to effectively block seizures in several rodent models of epilepsy (J. NAKAMURA, S. TAMU , T. KANDA, A. ISHII, K. ISHIHARA, T. SERIKAWA, J. YAMADA, and M. SASA, Eur. J. Pharmacol. 254 83-89, 1994), and in an animal model of kindled epilepsy (A. WAUQUIER and S. ZHOU, Epilepsy Res. 24, 73-77, 1996).
Detailed description1,587 words
#The sulfamates of the invention are of the following formula (I):