Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1997-06-05
2000-05-02
Berch, Mark L
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
540578, 514250, 544345, 546143, A61K 31495, C07D47104, C07D48704, C07D21704
Patent
active
060573139
ABSTRACT:
Novel N-substituted azacycloalkyl ring fused 2,3-quinoxalinediones are disclosed represented by the formula: ##STR1## or a pharmaceutically acceptable salt thereof, wherein R.sup.1 is hydrogen, alkyl or W-alkyl; X and Y are independently hydrogen, halogen, nitro, cyano, trifluoromethyl, SO.sub.2 CF.sub.3, SO.sub.2 R.sup.4, SO.sub.2 NR.sup.4 R.sup.5, alkyl, alkenyl, (CH.sub.2).sub.z CONR.sup.4 R.sup.5, (CH.sub.2).sub.z COOR.sup.4, or NHCOR.sup.4, wherein R.sup.4 and R.sup.5 are independently hydrogen, alkyl having 1 to 6 carbon atoms, cycloalkyl or W-alkyl, and z is an integer from 0 to 4; R.sup.2 is benzoyl, W, W-alkyl, COcycloalkyl, COalkyl-W, CONR.sup.3 alkyl, CONR.sup.3 -W, CONR.sup.3 alkyl-W, CSNR.sup.3 alkyl, CSNR.sup.3 alkyl-W, ##STR2## or a moiety derived from a common amino acid by removal of the --OH from the carboxyl group which is alpha to the amino, wherein --W is aryl, heteroaryl, or the heterocycles piperidinyl, piperazinyl, morpholinyl or pyrrolidinyl, wherein R.sup.3 is hydrogen, alkyl or W-alkyl; and m and n are independently 0, 1 or 2 provided that m+n is >1; provided that when R.sup.2 is benzoyl, ##STR3## or X is nitro, Y and R.sup.1 are H, m is 2 and n is 1;
when R.sup.2 is ##STR4## X is nitro, Y and R.sup.1 are H and m is 2 and n is 1; or when R.sup.2 is ##STR5## X is bromo, Y and R.sup.1 are H, m is 1 and n is 2. The novel N-substituted azacycloalkyl ring fused 2,3-quinoxalinediones may be used, for example, as neuroprotective agents, for treatment of chronic neurodegenerative disorders, as anticonvulsants and in the treatment of schizophrenia, epilepsy, anxiety, pain and drug addiction.
REFERENCES:
patent: 4889855 (1989-12-01), Jacobsen et al.
patent: 5081123 (1992-01-01), Honore et al.
patent: 5308845 (1994-05-01), Honore et al.
Advanced Organic Chemistry, Second Edition, Carey et al, Plenum Press, pp. 493-497, 1984.
M. A. Rogawski, TiPS 14, 325 (1993).
H. Li and A.M. Buchan, J. Cerebr. Blood Flow Metab. 13, 933 (1993).
B. Nellgard and T. Wieloch, J. Cerebr. Blood Flow Metab. 12, 2 (1992).
R. Bullock et al., J. Cerebr. Blood Flow Metab. 14, 466 (1994).
D. Xue et al., J. Cerebr. Blood Flow Metab. 14, 251 (1994).
X.-J. Xu et al., J. Pharmacol. Exp. Ther. 267, 140 (1993).
T. Namba et al., Brain Res. 638, 36 (1994).
S. E. Browne and J. McCulloch, Brain Res. 641, 10 (1994).
S.I. Yamaguchi et al., Epilepsy Res. 15, 179 (1993).
S.E. Smith et al., Eur. J. Pharmacol. 201, 179 (1991).
T. Klockgether et al., Ann Neurol. 34 (4), 585-593 (1993).
P.T. Francis et al., J. Neurochem. 60 (5), 1589-1604 (1993).
S. Lipton, TINS 16 (12), 527-532 (1993).
S. Lipton et al., New Eng. J. Med. 330 (9), 613-622 (1994).
C.F. Bigge, Biochem Pharmacol. 45, 1547-1561 (1993).
A.M. Buchan et al., Neurosci. Lett (Ireland) 132 (2), 255-8 (1991).
L. Dalgaard et al., Drug Metabolism and Disposition 22 (2), 289-93 (1994).
K. Lippert et al., Eur. J. Pharmacol. 253 (3), 207-13 (1994).
W. Loescher et al., Eur. J. Neurosci. 5(11), 1545-50 (1993).
J. Mosinger et al., Exp. Neurol. 113, 10-17 (1991).
C.F. Bigge and T.C. Malone, Curr. Opin. Ther. Pat., 951 (1993).
C. F. Bigge, et al., J Med Chem, 1995, 38, 3720-3740.
"Drug Evaluations Annual, 1993" (A.M.A). pp. 259, 260, 432, 2127.
Bigge Christopher Franklin
Malone Thomas Charles
Schelkun Robert Michael
Yi Chung Stephen
Anderson Elizabeth M.
Berch Mark L
Warner-Lambert & Company
LandOfFree
Glutamate (ampa/kainate) receptor antagonists: N-substituted fus does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Glutamate (ampa/kainate) receptor antagonists: N-substituted fus, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Glutamate (ampa/kainate) receptor antagonists: N-substituted fus will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1593973