Claims
- 1. A compound having the following formula:
- 2. The compound of claim 1, wherein only one or two of X, X′, X″, X′″ and X″″ are nitrogen or nitrogen bonded to oxygen.
- 3. The compound of claim 1, wherein not more than one of X, X′, X″, X′″ and X″″ are nitrogen bonded to oxygen.
- 4. The compound of claim 1, wherein X′′ is nitrogen or nitrogen bonded to oxygen.
- 5. The compound of claim 1, wherein both X′ and X′″ are nitrogen.
- 6. The compound of claim 1, wherein X, X″ and X″″ are carbon bonded to a substituent species.
- 7. The compound of claim 6, where the substituent species at X, X″ and X″″ are hydrogen.
- 8. The compound of claim 1, wherein X′″ is carbon bonded to a substituent species and X and X′ are both nitrogen, or X′ is carbon bonded to a substituent species and X and X′″ are both nitrogen.
- 9. The compound of claim 1, wherein no more than three of Y, Y′, Y″ and Y′″ are oxygen, sulfur, nitrogen or nitrogen bonded to a substituent species.
- 10. The compound of claim 1, wherein between one and three of Y, Y′, Y″ and Y′″ are nitrogen.
- 11. A pharmaceutical composition including a compound of claim 1.
- 12. A method of treating or preventing a CNS disorder associated with the release of neurotransmitters mediated by nicotinic receptors, comprising administering an effective amount of a compound of claim 1 to a patient in need of treatment thereof.
- 13. The method of claim 12, wherein the CNS disorder is selected from the group consisting of pre-senile dementia (early onset Alzheimer's disease), senile dementia (dementia of the Alzheimer's type), Lewy Body dementia, HIV-dementia, multiple cerebral infarcts, Parkinsonism including Parkinson's disease, Pick's disease, Huntington's chorea, tardive dyskinesia, hyperkinesia, mania, attention deficit disorder, anxiety, depression, mild cognitive impairment, dyslexia, schizophrenia and Tourette's syndrome.
- 14. The method of claim 12, wherein the compound is administered at a dosage effective at treating or preventing the CNS disorder but at a dosage that does not result in appreciable amounts of side effects associated with simulation of muscle or ganglionic receptors.
- 15. A method of causing analgesia, reducing inflammation, treating treat ulcerative colitis, inflammatory and auto-immune diseases, treating neurodegenerative diseases, and/or treating convulsions, comprising administering an effective amount of a compound of claim 1 to a patient in need of treatment thereof.
- 16. A method of treating bacterial, fungal and/or viral infections, and/or the effects of toxins produced by such infections, comprising administering an effective amount of a compound of claim 1 to a patient in need of treatment thereof.
- 17. A method of treating inflammatory bowel disease, pouchitis, acute cholangitis, aphthous stomatitis, arthritis, neurodegenerative diseases, Creutzfeld-Jakob disease, cachexia secondary to infection, genetic diseases and disorders, and/or auto-immune disorders comprising administering an effective amount of a compound of claim 1 to a patient in need of treatment thereof.
- 18. A method of inhibiting cytokine release, comprising administering an effective amount of a compound of claim 1 to a patient in need of treatment thereof.
- 19. A method of treating ulcerative colitis, comprising administering an effective amount of a compound of claim 1 to a patient in need of treatment thereof.
- 20. A method of causing analgesia, comprising administering an effective amount of a compound of claim 1 to a patient in need of treatment thereof.
- 21. A compound having the following formula:
- 22. The compound of claim 21, wherein only one or two of X, X′, X″, X′″ and X″″ are nitrogen or nitrogen bonded to oxygen.
- 23. The compound of claim 21, wherein not more than one of X, X′, X″, X′″ and X″″ are nitrogen bonded to oxygen.
- 24. The compound of claim 21, wherein X′″ is nitrogen or nitrogen bonded to oxygen.
- 25. The compound of claim 21, wherein both X′ and X′″ are nitrogen.
- 26. The compound of claim 21, wherein X, X″ and X″″ are carbon bonded to a substituent species.
- 27. The compound of claim 26, where the substituent species at X, X″ and X″″ are hydrogen.
- 28. The compound of claim 21, wherein X′″ is carbon bonded to a substituent species and X and X′ are both nitrogen, or X′ is carbon bonded to a substituent species and X and X′″ are both nitrogen.
- 29. The compound of claim 21, wherein no more than three of Y, Y′, Y″ and Y′″ be oxygen, sulfur, nitrogen or nitrogen bonded to a substituent species.
- 30. The compound of claim 21, wherein between one and three of Y, Y′, Y″ and Y′″ are nitrogen.
- 31. A pharmaceutical composition including a compound of claim 21.
- 32. A method of treating or preventing a CNS disorder associated with the release of neurotransmitters mediated by nicotinic receptors, comprising administering an effective amount of a compound of claim 21 to a patient in need of treatment thereof.
- 33. The method of claim 32, wherein the CNS disorder is selected from the group consisting of pre-senile dementia (early onset Alzheimer's disease), senile dementia (dementia of the Alzheimer's type), Lewy Body dementia, HIV-dementia, multiple cerebral infarcts, Parkinsonism including Parkinson's disease, Pick's disease, Huntington's chorea, tardive dyskinesia, hyperkinesia, mania, attention deficit disorder, anxiety, depression, mild cognitive impairment, dyslexia, schizophrenia and Tourette's syndrome.
- 34. The method of claim 32, wherein the compound is administered at a dosage effective at treating or preventing the CNS disorder but at a dosage that does not result in appreciable amounts of side effects associated with simulation of muscle or ganglionic receptors.
- 35. A method of causing analgesia, reducing inflammation, treating treat ulcerative colitis, inflammatory and auto-immune diseases, treating neurodegenerative diseases, and/or treating convulsions, comprising administering an effective amount of a compound of claim 21 to a patient in need of treatment thereof.
- 36. A method of treating bacterial, fungal and/or viral infections, and/or the effects of toxins produced by such infections, comprising administering an effective amount of a compound of claim 21 to a patient in need of treatment thereof.
- 37. A method of treating inflammatory bowel disease, pouchitis, acute cholangitis, aphthous stomatitis, arthritis, neurodegenerative diseases, Creutzfeld-Jakob disease, cachexia secondary to infection, genetic diseases and disorders, and/or auto-immune disorders comprising administering an effective amount of a compound of claim 21 to a patient in need of treatment thereof.
- 38. A method of inhibiting cytokine release, comprising administering an effective amount of a compound of claim 21 to a patient in need of treatment thereof.
- 39. A method of treating ulcerative colitis, comprising administering an effective amount of a compound of claim 21 to a patient in need of treatment thereof.
- 40. A method of causing analgesia, comprising administering an effective amount of a compound of claim 21 to a patient in need of treatment thereof.
- 41. A compound selected from the group consisting of:
7-(3-pyridyl)-1,7-diazaspiro[4.4]nonane 7-(5-pyrimidinyl)-1,7-diazaspiro[4.4]nonane 7-(5-isoxazolyl)-1,7-diazaspiro[4.4]nonane 7-(5-isothiazolyl)-1,7-diazaspiro[4.4]nonane 7-(5-(1,2,4-oxadiazol)yl)-1,7-diazaspiro[4.4]nonane 7-(2-(1,3,4-oxadiazol)yl)-1,7-diazaspiro[4.4]nonane 7-(2-pyrazinyl)-1,7-diazaspiro[4.4]nonane 7-(3-pyridazinyl)-1,7-diazaspiro[4.4]nonane 7-(5-methoxy-3-pyridyl)-1,7-diazaspiro[4,4]nonane 7-(5-cyclopentyloxy-3-pyridyl)-1,7-diazaspiro[4.4]nonane 7-(5-phenoxy-3-pyridyl)-1,7-diazaspiro[4.4]nonane 7-(5-(4-hydroxyphenoxy)-3-pyridyl)-1,7-diazaspiro[4.4]nonane 7-(5-ethynyl-3-pyridyl)-1,7-diazaspiro[4.4]nonane 7-(6-chloro-3-pyridyl)-1,7-diazaspiro[4.4]nonane 7-(6-methoxy-3-pyridazinyl)-1,7-diazaspiro[4.4]nonane 1-(3-pyridyl)-1,7-diazaspiro[4.4]nonane 1-(5-pyrimidinyl)-1,7-diazaspiro[4.4]nonane 1-(5-isoxazolyl)-1,7-diazaspiro[4.4]nonane 1-(5-isothiazolyl)-1,7-diazaspiro[4.4]nonane 1-(5-(1,2,4-oxadiazol)yl)-1,7-diazaspiro[4.4]nonane 1-(2-(1,3,4-oxadiazol)yl)-1,7-diazaspiro[4.4]nonane 1-(2-pyrazinyl)-1,7-diazaspiro[4.4]nonane 1-(3-pyridazinyl)-1,7-diazaspiro[4.4]nonane 1-methyl-7-(3-pyridyl)-1,7-diazaspiro[4.4]nonane 1-methyl-7-(5-pyrimidinyl)-1,7-diazaspiro[4.4]nonane 1-methyl-7-(5-isoxazolyl)-1,7-diazaspiro[4.4]nonane 1-methyl-7-(5-isothiazolyl)-1,7-diazaspiro[4.4]nonane 1-methyl-7-(5-(1,2,4-oxadiazol)yl)-1,7-diazaspiro[4.4]nonane 1-methyl-7-(2-(1,3,4-oxadiazol)yl)-1,7-diazaspiro[4.4]nonane 1-methyl-7-(2-pyrazinyl)-1,7-diazaspiro[4.4]nonane 1-methyl-7-(3-pyridazinyl)-1,7-diazaspiro[4,4]nonane 1-methyl-7-(5-methoxy-3-pyridyl)-1,7-diazaspiro[4.4]nonane 1-methyl-7-(5-cyclopentyloxy-3-pyridyl)-1,7-diazaspiro[4.4]nonane 1-methyl-7-(5-phenoxy-3-pyridyl)-1,7-diazaspiro[4.4]nonane 1-methyl-7-(5-(4-hydroxyphenoxy)-3-pyridyl)-1,7-diazaspiro[4.4]nonane 1-methyl-7-(5-ethynyl-3-pyridyl)-1,7-diazaspiro[4.4]nonane 1-methyl-7-(6-chloro-3-pyridyl)-1,7-diazaspiro[4.4]nonane 1-methyl-7-(6-methoxy-3-pyridazinyl)-1,7-diazaspiro[4.4]nonane 7-methyl-1-(3-pyridyl)-1,7-diazaspiro[4.4]nonane 7-methyl-1-(5-pyrimidinyl)-1,7-diazaspiro[4.4]nonane 7-methyl-1-(5-isoxazolyl)-1,7-diazaspiro[4.4]nonane 7-methyl-1-(5-isothiazolyl)-1,7-diazaspiro[4.4]nonane 7-methyl-1-(5-(1,2,4-oxadiazol)yl)-1,7-diazaspiro[4.4]nonane 7-methyl-1-(2-(1,3,4-oxadiazol)yl)-1,7-diazaspiro[4.4]nonane 7-methyl-1-(2-pyrazinyl)-1,7-diazaspiro[4.4]nonane 7-methyl-1-(3-pyridazinyl)-1,7-diazaspiro[4.4]nonane 2-(3-pyridyl)-2,7-diazaspiro[4.4]nonane 2-(5-pyrimidinyl)-2,7-diazaspiro[4.4]nonane 2-(5-isoxazolyl)-2,7-diazaspiro[4.4]nonane 2-(5-isothiazolyl)-2,7-diazaspiro[4.4]nonane 2-(5-(1,2,4-oxadiazol)yl)-2,7-diazaspiro[4.4]nonane 2-(2-(1,3,4-oxadiazol)yl)-2,7-diazaspiro[4.4]nonane 2-(2-pyrazinyl)-2,7-diazaspiro[4.4]nonane 2-(3-pyridazinyl)-2,7-diazaspiro[4.4]nonane 2-(5-methoxy-3-pyridyl)-2,7-diazaspiro[4.4]nonane 2-(5-cyclopentyloxy-3-pyridyl)-2,7-diazaspiro[4.4]nonane 2-(5-phenoxy-3-pyridyl)-2,7-diazaspiro[4.4]nonane 2-(5-(4-hydroxyphenoxy)-3-pyridyl)-2,7-diazaspiro[4.4]nonane 2-(5-ethynyl-3-pyridyl)-2,7-diazaspiro[4.4]nonane 2-(6-chloro-3-pyridyl)-2,7-diazaspiro[4.4]nonane 2-(6-methoxy-3-pyridazinyl)-2,7-diazaspiro[4.4]nonane 2-methyl-7-(3-pyridyl)-2,7-diazaspiro[4.4]nonane 2-methyl-7-(5-methoxy-3-pyridyl)-2,7-diazaspiro[4.4]nonane 2-methyl-7-(5-phenoxy-3-pyridyl)-2,7-diazaspiro[4.4]nonane 6-(3-pyridyl)-1,6-diazaspiro[3.4]octane 1-methyl-6-(3-pyridyl)-1,6-diazaspiro[3.4] octane 2-(3-pyridyl)-2,5-diazaspiro[3.4]octane 5-methyl-2-(3-pyridyl)-2,5-diazaspiro[3.4]octane 6-(3-pyridyl)-1,6-diazaspiro[3.5]nonane 1-methyl-6-(3-pyridyl)-1,6-diazaspiro[3.5]nonane 2-(3-pyridyl)-2,5-diazaspiro[3.5]nonane 5-methyl-2-(3-pyridyl)-2,5-diazaspiro[3.5]nonane 2-(3-pyridyl)-2,6-diazaspiro[4.5]decane 6-methyl-2-(3-pyridyl)-2,6-diazaspiro[4.5]decane 7-(3-pyridyl)-1,7-diazaspiro[4.5]decane 1-methyl-7-(3-pyridyl)-1,7-diazaspiro[4.5]decane 8-(3-pyridyl)-1,8-diazaspiro[5.5]undecane 1-methyl-8-(3-pyridyl)-1,8-diazaspiro[5.5]undecane and pharmaceutically acceptable salts thereof.
- 42. A compound selected from the group consisting of:
1′-(3-pyridyl)-spiro[1-azabicyclo[2.2.1]heptane-2,3′-pyrrolidine]1′-(5-ethoxy-3-pyridyl)-spiro[1-azabicyclo[2.2.1]heptane-2,3′-pyrrolidine]1′-(5-cyclopentyloxy-3-pyridyl)-spiro[1-azabicyclo[2.2.1]heptane-2,3′-pyrrolidine]1′-(5-phenoxy-3-pyridyl)-spiro[1-azabicyclo[2.2.1]heptane-2,3′-pyrrolidine]1′-(5-(4-hydroxyphenoxy)-3-pyridyl)-spiro[1-azabicyclo[2.2.1]heptane-2,3′-pyrrolidine]1′-(5-pyrimidinyl)-spiro[1-azabicyclo[2.2.1]heptane-2,3′-pyrrolidine]1′-(5-isoxazolyl)-spiro[1-azabicyclo[2.2.1]heptane-2,3′-pyrrolidine]1′-(5-isothiazolyl)-spiro[1-azabicyclo[2.2.1]heptane-2,3′-pyrrolidine]1′-(5-(1,2,4-oxadiazol)yl)-spiro[1-azabicyclo[2.2.1]heptane-2,3′-pyrrolidine]1′-(2-(1,3,4-oxadiazol)yl)-spiro[1-azabicyclo[2.2.1]heptane-2,3′-pyrrolidine]1′-(2-pyrazinyl)-spiro[1-azabicyclo[2.2.1]heptane-2,3′-pyrrolidine]1′-(3-pyridazinyl)-spiro[1-azabicyclo[2.2.1]heptane-2,3′-pyrrolidine]1′-(5-ethynyl-3-pyridyl)-spiro[1-azabicyclo[2.2.1]heptane-2,3′-pyrrolidine]1′-(6-chloro-3-pyridyl)-spiro[1-azabicyclo[2.2.1]heptane-2,3′-pyrrolidine]1′-(6-methoxy-3-pyridazinyl)-spiro[1-azabicyclo[2.2.1]heptane-2,3′-pyrrolidine]1′-(3-pyridyl)-spiro[1-azabicyclo[2.2.2]octane-2,3′-pyrrolidine]1′-(5-methoxy-3-pyridyl)-spiro[1-azabicyclo[2.2.2]octane-2,3′-pyrrolidine]1′-(5-cyclopentyloxy-3-pyridyl)-spiro[1-azabicyclo[2.2.2]octane-2,3′-pyrrolidine]1′-(5-phenoxy-3-pyridyl)-spiro[1-azabicyclo[2.2.2]octane-2,3′-pyrrolidine]1′-(5-(4-hydroxyphenoxy)-3-pyridyl)-spiro[1-azabicyclo[2.2.2]octane-2,3′-pyrrolidine]1′-(5-ethynyl-3-pyridyl)-spiro[1-azabicyclo[2.2.2]octane-2,3′-pyrrolidine]1′-(6-chloro-3-pyridyl)-spiro[1-azabicyclo[2.2.2]octane-2,3′-pyrrolidine]1′-(5-pyrimidinyl)-spiro[1-azabicyclo[2.2.2]octane-2,3′-pyrrolidine]1′-(2-pyrazinyl)-spiro[1-azabicyclo[2.2.2]octane-2,3′-pyrrolidine]1′-(3-pyridazinyl)-spiro[1-azabicyclo[2.2.2]octane-2,3′-pyrrolidine]1′-(6-methoxy-3-pyridazinyl)-spiro[1-azabicyclo[2.2.2]octane-2,3′-pyrrolidine]1′-(5-isoxazolyl)-spiro[1-azabicyclo[2.2.2]octane-2,3′-pyrrolidine]1′-(5-isothiazolyl)-spiro[1-azabicyclo[2.2.2]octane-2,3′-pyrrolidine]1′-(5-(1,2,4-oxadiazol)yl)-spiro[1-azabicyclo[2.2.2]octane-2,3′-pyrrolidine]1′-(2-(1,3,4-oxadiazol)yl)-spiro[1-azabicyclo[2.2.2]octane-2,3′-pyrrolidine]1′-(3-pyridyl)-2′H-spiro[1-azabicyclo[2.2.1]heptane-7,3′-pyrrolidine]1′-(5-methoxy-3-pyridyl)-2′H-spiro[1-azabicyclo[2.2.1]heptane-7,3′-pyrrolidine]1′-(5-cyclopentyloxy-3-pyridyl)-2′H-spiro[1-azabicyclo[2.2.1]heptane-7,3′-pyrrolidine]1′-(5-phenoxy-3-pyridyl)-2′H-spiro[1-azabicyclo[2.2.1]heptane-7,3′-pyrrolidine]1′-(5-(4-hydroxyphenoxy)-3-pyridyl)-2′H-spiro[1-azabicyclo[2.2.1]heptane-7,3′-pyrrolidine]1′-(6-chloro-3-pyridyl)-2′H-spiro[1-azabicyclo[2.2.1]heptane-7,3′-pyrrolidine]1′-(5-pyrimidinyl)-2′H-spiro[1-azabicyclo[2.2.1]heptane-7,3′-pyrrolidine]1′-(2-pyrazinyl)-2′H-spiro[1-azabicyclo[2.2.1]heptane-7,3′-pyrrolidine]1′-(3-pyridazinyl)-2′H-spiro[1-azabicyclo[2.2.1]heptane-7,3′-pyrrolidine]1′-(6-methoxy-3-pyridazinyl)-2′H-spiro[1-azabicyclo[2.2.1]heptane-7,3′-pyrrolidine]1′-(5-isoxazolyl)-2′H-spiro[1-azabicyclo[2.2.1]heptane-7,3′-pyrrolidine]1′-(5-isothiazolyl)-2′H-spiro[1-azabicyclo[2.2.1]heptane-7,3′-pyrrolidine]1′-(5-(1,2,4-oxadiazol)yl)-2′H-spiro[1-azabicyclo[2.2.1]heptane-7,3′-pyrrolidine]1′-(2-(1,3,4-oxadiazol)yl)-2 ′H-spiro[1-azabicyclo[2.2.1]heptane-7,3′-pyrrolidine] and pharmaceutically acceptable salts thereof.
- 43. A pharmaceutical composition comprising an effective amount of a compound of claim 41.
- 44. A pharmaceutical composition comprising an effective amount of a compound of claim 42.
CROSS REFERENCE TO RELATED APPLICATION
[0001] This document claims priority to and the benefit of the filing date of co-pending provisional application entitled “N-Aryl Diazaspiracyclic Compounds and Methods of Preparation and Use Thereof” assigned serial No. 60/394,337, and filed Jul. 5, 2002, which is hereby incorporated by reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60394337 |
Jul 2002 |
US |