Details for Patent: 7,144,882
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Title: | Aryl fused azapolycyclic compounds |
Abstract: | This invention is directed to compounds of the formula (I): ##STR00001## and their pharmaceutically acceptable salts, wherein R.sup.1, R.sup.2, and R.sup.3 are as defined herein; intermediates for the synthesis of such compounds, pharmaceutical compositions containing such compounds; and methods of using such compounds in the treatment of neurological and psychological disorders. |
Inventor(s): | Coe; Jotham Wadsworth (Niantic, CT), Brooks; Paige Roanne Palmer (North Stonington, CT) |
Assignee: | Pfizer Inc (New York, NY) |
Filing Date: | Jan 03, 2003 |
Application Number: | 10/336,532 |
Claims: | 1. A compound selected from the group consisting of: (-)-5,13-diazatetracyclo[9.3.1.0.sup.2,10.0.sup.4,8]pentadeca-2,4(8),9-tr- ien-6-one; (-)-6-oxo-5-oxa-7,13-diazatetracyclo[9.3.1.0.sup.2,10.0.sup.4,8- ]pentadeca-2(10),3,8-triene; (-)-2-fluoro-N-(4-hydroxy-10-aza-tricyclo[6.3.1.0.sup.2,7]dodeca-2(7),3,5- -trien-5-yl)-benzamide; (-)-7-dimethylamino-5-thia-5-dioxo-6,13-diazatetracyclo[9.3.1.0.sup.2,10.- 0.sup.4,8]pentadeca-2(10),3,6,8-tetraene; (-)-5-oxa-7-methyl-6-oxo-7,13-diazatetracyclo[9.3.1.0.sup.2,10.0.sup.4,8]- pentadeca-2(10),3,8-triene; (-)-6-methyl-5-thia-7,13-diazatetracyclo[9.3.1.0.sup.2,10.0.sup.4,8]penta- deca-2(10),3,6,8-tetraene; (-)-6-methyl-7-propyl-5,7,13-triazatetracyclo[9.3.1.0.sup.2,10.0.sup.4,8]- pentadeca-2(10),3,5,8-tetraene; (-)-6,7-dimethyl-5,7,13-triazatetracyclo[9.3.1.0.sup.2,10.0.sup.4,8]penta- deca-2(10),3,5,8-tetraene; (-)-7-propyl-5,7,13-triazatetracyclo[9.3.1.0.sup.2,10.0.sup.4,8]pentadeca- -2(10),3,5,8-tetraene; (-)-7-butyl-5,7,13-triazatetracyclo[9.3.1.0.sup.2,10.0.sup.4,8]pentadeca-- 2(10),3,5,8-tetraene; (-)-6-methyl-7-isobutyl-5,7,13-triazatetracyclo[9.3.1.0.sup.2,10.0.sup.4,- 8]pentadeca-2(10),3,5,8-tetraene; (-)-7-phenyl-5,7,13-triazatetracyclo[9.3.1.0.sup.2,10.0.sup.4,8]pentadeca- -2(10),3,5,8-tetraene; (-)-6-methyl-7-phenyl-5,7,13-triazatetracyclo[9.3.1.0.sup.2,10.0.sup.4,8]- pentadeca-2(10),3,5,8-tetraene; (-)-7-neopentyl-5,7,13-triazatetracyclo[9.3.10.sup.2,10.0.sup.4,8]pentade- ca-2(10),3,5,8-tetraene; (-)-6-methyl-7-neopentyl-5,7,13-triazatetracyclo[9.3.1.0.sup.2,10.0.sup.4- ,8]pentadeca-2(10),3,5,8-tetraene; (-)-5-oxa-7,13-diazatetracyclo[9.3.1.0.sup.2,10.0.sup.4,8]pentadeca-2(10)- ,3,6,8-tetraene; (-)-6-methyl-5-oxa-7,13-diazatetracyclo[9.3.1.0.sup.2,10.0.sup.4,8]pentad- eca-2(10),3,6,8-tetraene; and pharmaceutically acceptable salts thereof. 2. A pharmaceutical composition comprising a pharmaceutically effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier. 3. A method for reducing nicotine addiction or aiding in the cessation or lessening of tobacco use in a mammal, comprising administering to said mammal an amount of a compound according to claim 1 that is effective in reducing nicotine addiction or aiding in the cessation or lessening of tobacco use. 4. A method for treating a disorder or condition selected from inflammatory bowel disease, ulcerative colitis, pyoderma gangrenosum, Crohn's disease, irritable bowel syndrome, spastic dystonia, chronic pain, acute pain, celiac sprue, pouchitis, vasoconstriction, anxiety, panic disorder, depression, bipolar disorder, autism, sleep disorders, jet lag, amyotrophic lateral sclerosis, cognitive dysfunction, hypertension, bulimia, anorexia, obesity, cardiac arrythmias, gastric acid hypersecretion, ulcers, pheochromocytoma, progressive supranuclear palsy; chemical dependencies and addictions; dependencies or, or addictions to, nicotine, tobacco products, alcohol, benzodiazepines, barbiturates, opioids or cocaine; headache, migraine, stroke, traumatic brain injury, obsessive-compulsive disorder, psychosis, Huntington's chorea, tardive dyskinesia, hyperkinesia, dyslexia, schizophrenia, multi-infarct dementia, age-related cognitive decline, epilepsy, including petit mal absence epilepsy, senile dementia of the Alzheimer's type, Parkinson's disease, attention deficit hyperactivity disorder and Tourette's Syndrome in a mammal, comprising administering to a mammal in need of such treatment an amount of a compound according to claim 1 that is effective in treating such disorder or condition. 5. A method for treating attention deficit hyperactivity disorder in a mammal, comprising administering to said mammal an amount of a compound according to claim 1 that is effective in attention deficit hyperactivity disorder. 6. A method for treating Tourette's Syndrome in a mammal, comprising administering to said mammal an amount of a compound according to claim 1 and pharmaceutically acceptable salts therof. 7. A compound selected from the group consisting of: (-)-4-methyl-10-aza-tricyclo[6.3.1.0.sup.2,7]dodeca-2(7),3,5-triene; (-)-4-nitro-10-azatricyclo[6.3.1.0.sup.2,7]dodeca-2(7),3,5-triene; (-)-4-amino-10-azatricyclo[6.3.1.0.sup.2,7]dodeca-2(7),3,5-triene; (-)-N.sup.1-[10-azatricyclo[6.3.1.0.sup.2,7]dodeca-2(7),3,5-trien-4-yl]ac- etamide; (-)-4-chloro-10-azatricyclo[6.3.1.0.sup.2,7]dodeca-2(7),3,5-trien- e; (-)-3-(10-azatricyclo[6.3.1.0.sup.2,7]dodeca-2(7),3,5-trien-4-yl)-5-met- hyl-1,2,4-oxadiazole; (-)-10-azatricyclo[6.3.1.0.sup.2,7]dodeca-2(7),3,5-trien-4-ol; (-)-N.sup.4,N.sup.4-dimethyl-10-azatricyclo[6.3.1.0.sup.2,7]dodeca-2(7),3- ,5-triene-4-sulfonamide; (-)-4-(1-pyrrolidinylsulfonyl)-10-azatricyclo[6.3.1.0.sup.2,7]dodeca-2(7)- ,3,5-triene; (-)-5-fluoro-10-aza-tricyclo[6.3.1.0.sup.2,7]dodeca-2(7),3,5-triene-4-car- bonitrile; (-)-4-ethynyl-5-fluoro-10-aza-tricyclo[6.3.1.0.sup.2,7]dodeca-2- (7),3,5-triene; (-)-5-ethynyl-10-aza-tricyclo[6.3.1.0.sup.2,7]dodeca-2(7),3,5-triene-4-ca- rbonitrile; (-)-5-chloro-10-aza-tricyclo[6.3.1.0.sup.2,7]dodeca-2(7),3,5-triene-4-car- bonitrile; (-)-4-ethynyl-5-chloro-10-aza-tricyclo[6.3.1.0.sup.2,7]dodeca-2- (7),3,5-triene; (-)-4-fluoro-5-trifluoromethyl-10-aza-tricyclo[6.3.1.0.sup.2,7]dodeca-2(7- ),3,5-triene; (-)-4-chloro-5-trifluoromethyl-10-aza-tricyclo[6.3.1.0.sup.2,7]dodeca-2(7- ),3,5-triene; (-)-5-trifluoromethyl-10-aza-tricyclo[6 .3.1.0.sup.2,7]dodeca-2(7),3,5-triene-4-carbonitrile; (-)-4-ethynyl-5-trifluoromethyl-10-aza-tricyclo[6.3.1.0.sup.2,7]dodeca-2(- 7),3,5-triene; and pharmaceutically acceptable salts thereof. 8. A pharmaceutical composition comprising a pharmaceutically effective amount of a compound according to claim 7 and a pharmaceutically acceptable carrier. 9. A method for reducing nicotine addiction or aiding in the cessation or lessening of tobacco use in a mammal, comprising administering to said mammal an amount of a compound according to claim 7 that is effective in reducing nicotine addiction or aiding in the cessation or lessening of tobacco use. 10. A method for treating a disorder or condition selected from inflammatory bowel disease, ulcerative colitis, pyoderma gangrenosum, Crohn's disease, irritable bowel syndrome, spastic dystonia, chronic pain, acute pain, celiac sprue, pouchitis, vasoconstriction, anxiety, panic disorder, depression, bipolar disorder, autism, sleep disorders, jet lag, amyotrophic lateral sclerosis, cognitive dysfunction, hypertension, bulimia, anorexia, obesity, cardiac arrythmias, gastric acid hypersecretion, ulcers, pheochromocytoma, progressive supranuclear palsy; chemical dependencies and addictions; dependencies or, or addictions to, nicotine, tobacco products, alcohol, benzodiazepines, barbiturates, opioids or cocaine; headache, migraine, stroke, traumatic brain injury, obsessive-compulsive disorder, psychosis, Huntington's chorea, tardive dyskinesia, hyperkinesia, dyslexia, schizophrenia, multi-infarct dementia, age-related cognitive decline, epilepsy, including petit mal absence epilepsy, senile dementia of the Alzheimer's type, Parkinson's disease, attention deficit hyperactivity disorder and Tourette's Syndrome in a mammal, comprising administering to a mammal in need of such treatment an amount of a compound according to claim 7 that is effective in treating such disorder or condition. 11. A method for treating attention deficit hyperactivity disorder in a mammal, comprising administering to said mammal an amount of a compound according to claim 7 that is effective in attention deficit hyperactivity disorder. 12. A method for treating Tourette's Syndrome in a mammal, comprising administering to said mammal an amount of a compound according to claim 7 that is effective in treating Tourette's Syndrome. 13. A compound selected from the group consisting of: (-)-3-trifluoromethyl-10-aza-tricyclo[6.3.1.0.sup.2,7]dodeca-2(7),3,5-tri- ene; (-)-4-trifluoromethyl-10-aza-tricyclo[6.3.1.0.sup.2,7]dodeca-2(7),3,5- -triene; (-)-3-fluoro-10-aza-tricyclo[6.3.1.0.sup.2,7]dodeca-2(7),3,5-trie- ne; (-)-10-azatricyclo[6.3.1.0.sup.2,7]dodeca-2(7),3,5-trien-4-yl cyanide; (-)-4-fluoro-10-aza-tricyclo[6.3.1.0.sup.2,7]dodeca-2(7),3,5-triene; and pharmaceutically acceptable salts thereof. 14. A pharmaceutical composition comprising a pharmaceutically effective amount of a compound to claim 13 and a pharmaceutically acceptable carrier. 15. A method for reducing nicotine addiction or aiding in the cessation or lessening of tobacco use in a mammal, comprising administering to said mammal an amount of a compound according to claim 13 that is effective in reducing nicotine addiction or aiding in the cessation or lessening of tobacco use. 16. A method for treating a disorder or condition selected from inflammatory bowel disease, ulcerative colitis, pyoderma gangrenosum, Crohn's disease, irritable bowel syndrome, spastic dystonia, chronic pain, acute pain, celiac sprue, pouchitis, vasoconstriction, anxiety, panic disorder, depression, bipolar disorder, autism, sleep disorders, jet lag, amyotrophic lateral sclerosis, cognitive dysfunction, hypertension, bulimia, anorexia, obesity, cardiac arrythmias, gastric acid hypersecretion, ulcers, pheochromocytoma, progressive supranuclear palsy; chemical dependencies and addictions; dependencies or, or addictions to, nicotine, tobacco products, alcohol, benzodiazepines, barbiturates, opioids or cocaine; headache, migraine, stroke, traumatic brain injury, obsessive-compulsive disorder, psychosis, Huntington's chorea, tardive dyskinesia, hyperkinesia, dyslexia, schizophrenia, multi-infarct dementia, age-related cognitive decline, epilepsy, including petit mal absence epilepsy, senile dementia of the Alzheimer's type, Parkinson's disease, attention deficit hyperactivity disorder and Tourette's Syndrome in a mammal, comprising administering to a mammal in need of such treatment an amount of a compound according to claim 13 that is effective in treating such disorder or condition. 17. A method for treating attention deficit hyperactivity disorder in a mammal, comprising administering to said mammal an amount of a compound according to claim 13 that is effective in attention deficit hyperactivity disorder. 18. A method for treating Tourette's Syndrome in a mammal, comprising administering to said mammal an amount of a compound according to claim 13 that is effective in treating Tourette's Syndrome. 19. A compound selected from the group consisting of: (-)-5,14-diazatetracyclo[10.3.1.0.sup.2,11.0.sup.4,9]hexadeca-2(11),3,5,7- ,9-pentaene; (-)-6-methyl-5,14-diazatetracyclo[10.3.1.0.sup.2,11.0.sup.4,9]hexadeca-2(- 11),3,5,7,9-pentaene; (-)-7-methyl-5,14-diazatetracyclo[10.3.1.0.sup.2,11.0.sup.4,9]hexadeca-2(- 11),3,5,7,9-pentaene; (-)-7-ethyl-5,14-diazatetracyclo[10.3.1.0.sup.2,11.0.sup.4,9]hexadeca-2(1- 1),3,5,7,9-pentaene; (-)-8-methyl-5,14-diazatetracyclo[10.3.1.0.sup.2,11.0.sup.4,9]hexadeca-2(- 11),3,5,7,9-pentaene; (-)-5,14-diazatetracyclo[10.3.1.0.sup.2,11.0.sup.4,9]hexadeca-2(11),3,7,9- -tetraen-6-one; (-)-6-chloro-5,14-diazatetracyclo[10.3.1.0.sup.2,11.0.sup.4,9]hexadeca-2(- 11),3,5,7,9-pentaene; (-)-6-methoxy-5,14-diazatetracyclo[10.3.1.0.sup.2,11.0.sup.4,9]hexadeca-2- (11),3,5,7,9-pentaene; (-)-6-chloro-10-fluoro-5,14-diazatetracyclo[10.3.1.0.sup.2,11.0.sup.4,9]h- exadeca-2(11),3,5,7,9-pentaene; (-)-6-chloro-3-fluoro-5,14-diazatetracyclo[10.3.1.0.sup.2,11.0.sup.4,9]he- xadeca-2(11),3,5,7,9-pentaene; and pharmaceutically acceptable salts thereof. 20. A pharmaceutical composition comprising a pharmaceutically effective amount of a compound according to claim 19 and a pharmaceutically acceptable carrier. 21. A method for reducing nicotine addiction or aiding in the cessation or lessening of tobacco use in a mammal, comprising administering to said mammal an amount of a compound according to claim 19 that is effective in reducing nicotine addiction or aiding in the cessation or lessening of tobacco use. 22. A method for treating a disorder or condition selected from inflammatory bowel disease, ulcerative colitis, pyoderma gangrenosum, Crohn's disease, irritable bowel syndrome, spastic dystonia, chronic pain, acute pain, celiac sprue, pouchitis, vasoconstriction, anxiety, panic disorder, depression, bipolar disorder, autism, sleep disorders, jet lag, amyotrophic lateral sclerosis, cognitive dysfunction, hypertension, bulimia, anorexia, obesity, cardiac arrythmias, gastric acid hypersecretion, ulcers, pheochromocytoma, progressive supranuclear palsy; chemical dependencies and addictions; dependencies or, or addictions to, nicotine, tobacco products, alcohol, benzodiazepines, barbiturates, opioids or cocaine; headache, migraine, stroke, traumatic brain injury, obsessive-compulsive disorder, psychosis, Huntington's chorea, tardive dyskinesia, hyperkinesia, dyslexia, schizophrenia, multi-infarct dementia, age-related cognitive decline, epilepsy, including petit mal absence epilepsy, senile dementia of the Alzheimer's type, Parkinson's disease, attention deficit hyperactivity disorder and Tourette's Syndrome in a mammal, comprising administering to a mammal in need of such treatment an amount of a compound according to claim 19 that is effective in treating such disorder or condition. 23. A method for treating attention deficit hyperactivity disorder in a mammal, comprising administering to said mammal an amount of a compound according to claim 19 that is effective in attention deficit hyperactivity disorder. 24. A method for treating Tourette's Syndrome in a mammal, comprising administering to said mammal an amount of a compound according to claim 19 that is effective in treating Tourette's Syndrome. |