PCP receptor ligands and the use thereof
AssigneeState of Oregon, acting by and through the Oregon State Board of Higher Education, acting for and on behalf of the Oregon Health Sciences University and the University of Oregon
InventorsEckard Weber, John F. W. Keana, Peter Barmettler
Life of this patent
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Abstract
The invention relates to 5-(iminomethano)-10,11-dihydro-5H-dibenzoa,d!cycloheptene and derivatives thereof. The invention also relates to the use of such compounds for the treatment or prevention of neuronal loss in ischemia, hypoxia, brain or spinal chord trauma, as well as for the treatment of Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease and Down's syndrome.
Claims23
A compound selected from the group consisting of
- 3-chloro-5-(iminomethano)-10,11-dihydro-5H-dibenzoa,d!cycloheptene;
- (+) 3-chloro-5-(iminomethano)-10,11-dihydro-5H-dibenzoa,d!cycloheptene;
- 7-methoxy-5-(iminomethano)-10,11-dihydro-5H-dibenzoa,d!cycloheptene;
- 3-bromo-5-(iminomethano)-10,11-dihydro-5H-dibenzoa,d!cycloheptene;
- 3-chloro-7-methoxy-5-(iminomethano)-10,11-dihydro-5H-dibenzoa,d!cyclohepte ne;
- 3-bromo-7-methoxy-5-(iminomethano)-10,11-dihydro-5H-dibenzoa,d!cyclohepten e;
- 7-chloro-5-(iminomethano)-10,11-dihydro-5H-dibenzoa,d!cycloheptene;
- 3-bromo-7-amino-5-(iminomethano)-10,11-dihydro-5H-dibenzoa,d!cycloheptene;
- 3-bromo-7-methoxy-N-methyl-5-(iminomethano)-10,11-dihydro-5H-dibenzoa,d!cy cloheptene;
- 3-fluoro-5-(iminomethano)-10,11-dihydro-5H-dibenzoa,d!cycloheptene;
- (+)3-fluoro-5-(iminomethano)-10,11-dihydro-5H-dibenzoa,d!cycloheptene;
- 3-methoxy-5-(iminomethano)-10,11-dihydro-5H-dibenzoa,d!cycloheptene;
- 3-iodo-5-(iminomethano)-10,11-dihydro-5H-dibenzoa,d!cycloheptene;
- (-)-3-chloro-5-(iminomethano)-10,11-dihydro-5H-dibenzoa,d!cycloheptene;
- (.+-.)-N-methyl-3-fluoro-5-(iminomethano)-10,11-dihydro-5H-dibenzoa,d!cycl oheptene;
- (+)-N-methyl-3-fluoro-5-(iminomethano)-10,11-dihydro-5H-dibenzoa,d!cyclohe ptene;
- (.+-.)-N-methyl-3-chloro-5-(iminomethano)-10,11-dihydro-5H-dibenzoa,d!cycl oheptene;
- (+)-N-methyl-3-chloro-5-(iminomethano)-10,11-dihydro-5H-dibenzoa,d!cyclohe ptene;
- 3-nitro-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- 3-azido-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- 3-trifluoromethyl-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cyclohepte ne;
- N-methyl-3-trifluoromethyl-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!c ycloheptene;
- 3,7-difluoro-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- 3-phenyl-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- 3-amino-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- 8-hydroxy-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- 3-hydroxy-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- 8-methoxy-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- 3-cyano-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- 3-methylthio-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- (+)-5-(iminomethano)-10,11-dihydro-5H-dibenzoa,d!cycloheptene;
- N-methyl-5-(iminomethano)-10,11-dihydro-5H-dibenzoa,d!cycloheptene;
- and
- N-methyl-3-iodo-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene
- or a pharmaceutically acceptable salt thereof and/or the optically active isomer thereof.
A method of treating neuronal loss, comprising administering to a mammal in need of such treatment an effective of 3-chloro-5-(iminomethano)-10, 11-dihydro-5H-dibenzo-a,d!cycloheptene;
- (+) 3-chloro-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- 7-methoxy-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- 3-bromo-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- 3-fluoro-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- (+) 3-fluoro-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- 3-methoxy-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- 3-iodo-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- or
- N-methyl-3-fluoro-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cyclohepte ne;
- or a pharmaceutically acceptable salt thereof.
A method of treating a mammal suffering from ischemia, stroke, heart attack, hypoxia, hypoglycemia or brain or spinal cord trauma, comprising administering to the mammal an effective amount of
- 3-chloro-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- (+) 3-chloro-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- 7-methoxy-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- 3-bromo-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- 3-fluoro-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a, d!cycloheptene;
- (+) 3-fluoro-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- 3-methoxy-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- 3-iodo-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- or
- N-methyl-3-fluoro-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cyclohepte ne;
- or a pharmaceutically acceptable salt thereof.
A method of treating a mammal suffering from Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease or Down's syndrome, comprising administering to the mammal an effective amount of
- 3-chloro-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- (+) 3-chloro-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- 7-methoxy-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- 3-bromo-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- 3-fluoro-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- (+) 3-fluoro-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- 3-methoxy-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- 3-iodo-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cycloheptene;
- or
- N-methyl-3-fluoro-5-(iminomethano)-10,11-dihydro-5H-dibenzo-a,d!cyclohepte ne;
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.