Claims
- 1. A compound of Formula I
- 2. The compound according to claim 1 of Formula II
- 3. The compound according to claim 2 wherein
Y is selected from —N(H)—, —CH(OH)—, and —N(OH)—, and E is selected from —CH═CH—, —CH2—CH2—, —CH═N—, —C(O)—CH2—, —CH2—C(O)—, —CH2—S(O)—, —CH2—S(O)2—, —N═C(H)—, —N(H)—C(O)—, —O—C(O)—, —S—C(O)—, —N═N—, —CH═CH—C(H)—, —CH2—CH2—CH2—, —CH2—CH2—C(O)—, —CH2—CH2—S(O)—, —CH2—CH2—S(O)2—, —CH═CH—C(O)—, —N═CH—C(O)—, —O—CH2—C(O)—, —S—CH2—C(O)—, and —N(H)—C(O)—C(O)—; or Y is selected from═C(OH)—; and E is selected from —CH═CH—C(H)═, —C(O)—C(H)═, —C(O)—N═, —O—N═, —S—N═, —C(O)—N(H)—N═, —CH═N—N═, —CH═N(O)—N═, and —N(H)—C(O)—N═.
- 4. The compound according to claim 2 wherein
-E-Y- is selected from the group consisting of
—CH═CH—N(H)—, —(CH2)2—N(H)—, —CH═N—N(H)—, —C(O)—CH2—N(H)—, —CH2—C(O)—N(H)—, —CH2—S(O)—N(H)—, —CH2—S(O)2—N(H)—, —CH═CH—CH(OH)—, —(CH2)2—CH(OH)—, —C(O)—C(H)═C(OH)—, —C(O)—N═C(OH)—, —N═CH—N(H)—, —N(H)—C(O)—N(H)—, —O—C(O)—NH—, —S—C(O)—NH—, —O—N═CH(OH)—, —S—N═CH(OH)—, —N═N—N(H)—, —N═N—N(OH)—, —CH═CH—CH═C(OH)—, —(CH2)3—CH(OH)—, —(CH2)2—C(O)—N(H)—, —(CH2)2—S(O)—N(H)—, —(CH2)2—S(O)2—N(H)—, —CH═CH—C(O)—N(H)—, —C(O)—NH—N═C(OH)—, —CH═N—N═C(OH)—, —CH═N(O)—N═C(OH)—, —N(H)—C(O)—N═C(OH)—, —N═CH—C(O)—NH—, —O—CH2—C(O)—NH—, —S—CH2—C(O)—NH—, and —N(H)—C(O)—C(O)—N(H)—.
- 5. The compound according to claim 1 of Formula III
- 6. The compound according to claim 5, which is trans-6-(5-{[methyl-4-phenyl-cyclohexyl)-amino]-methyl-4,5-dihydro-isoxazol-3-yl}-3H-benzoxazol-2-one.
- 7. The compound according to claim 1 of Formula IV
- 8. The compound according to claim 7 selected from the group consisting of:
trans-6-{5-[4-(4-fluoro-phenyl)-cyclohexylamino]methyl-2-oxo-oxazolidin-3-yl}-3H-benzoxazol-2-one; trans-6-{5-[4-(4-fluoro-phenyl)-cyclohexylamino]methyl-2-oxo-oxazolidin-3-yl}-3H-benzoxazol-2-one hydrochloride; trans-6-(5-{[4-(4-fluoro-phenyl)-cyclohexyl]-methyl-amino}methyl-2-oxo-oxazolidin-3-yl)-3H-benzoxazol-2-one; and trans-6-(5-{[4-(4-fluoro-phenyl)-cyclohexyl]-methyl-amino}methyl-2-oxo-oxazolidin-3-yl)-3H-benzoxazol-2-one hydrochloride.
- 9. The compound according to claim 1 of Formula V
- 10. A compound of Formula VI or Formula VIa
- 11. The compound according to claim 10 of Formula VII
- 12. The compound according to claim 11 wherein
Y is selected from —N(H)—, —CH(OH)—, and —N(OH)—, and E is selected from —CH═CH—, —CH2—CH2—, —CH═N—, —C(O)—CH2—, —CH2—C(O)—, —CH2—S(O)—, —CH2—S(O)2—, —N═C(H)—, —N(H)—C(O)—, —O—C(O)—, —S—C(O)—, —N═N—, —CH═CH—C(H)—, —CH2—CH2—CH2—, —CH2—CH2—C(O)—, —CH2—CH2—S(O)—, —CH2—CH2—S(O)2—, —CH═CH—C(O)—, —N═CH—C(O)—, —O—CH2—C(O)—, —S—CH2—C(O)—, and —N(H)—C(O)—C(O)—; or Y is selected from═C(OH)—, and E is selected from —CH═CH—C(H)═, —C(O)—C(H)═, —C(O)—N═, —O—N═, —S—N═, —C(O)—N(H)—N═, —CH═N—N═, —CH═N(O)—N═, and —N(H)—C(O)—N═.
- 13. The compound according to claim 11 wherein
-E-Y- is selected from the group consisting of
—CH═CH—N(H)—, —(CH2)2—N(H)—, —CH═N—N(H)—, —C(O)—CH2—N(H)—, —CH2—C(O)—N(H)—, —CH2—S(O)—N(H)—, —CH2—S(O)2—N(H)—, —CH═CH—CH(OH)—, —(CH2)2—CH(OH)—, —C(O)—C(H)═C(OH)—, —C(O)—N═C(OH)—, —N═CH—N(H)—, —N(H)—C(O)—N(H)—, —O—C(O)—NH—, —S—C(O)—NH—, —O—N═CH(OH)—, —S—N═CH(OH)—, —N═N—N(H)—, —N═N—N(OH)—, —CH═CH—CH═C(OH)—, —(CH2)3—CH(OH)—, —(CH2)2—C(O)—N(H)—, —(CH2)2—S(O)—N(H)—, —(CH2)2—S(O)2—N(H)—, —CH═CH—C(O)—N(H)—, —C(O)—NH—N═C(OH)—, —CH═N—N═C(OH)—, —CH═N(O)—N═C(OH)—, —N(H)—C(O)—N═C(OH)—, —N═CH—C(O)—NH—, —O—CH2—C(O)—NH—, —S—CH2—C(O)—NH—, and —N(H)—C(O)—C(O)—N(H)—.
- 14. The compound according to claim 10 of Formula VIII
- 15. The compound according to claim 14 which is trans-6-{4-[methyl-(2-methyl-5-phenyl-furan-3-ylmethyl)-amino]-cyclohexyl}-3H-benzoxazol-2-one.
- 16. The compound according to claim 10 of Formula IX
- 17. The compound according to claim 16 selected from the group consisting of:
trans-(R)-6-{4-[(2-oxo-3-phenyl-oxazolidin-5-ylmethyl)amino]-cyclohexyl}-3H-benzoxazol-2-one; and trans-(R)-6-{4-[methyl-(2-oxo-3-phenyl-oxazolidin-5-ylmethyl)amino]-cyclohexyl}-3H-benzoxazol-2-one.
- 18. The compound according to claim 10 of Formula X
- 19. The compound according to claim 18 selected from the group consisting of:
trans-6-{4-[(5-methyl-2-phenyl-thiazol-4-ylmethyl)-amino]-cyclohexyl}-3H-benzoxazol-2-one; and trans-6-{4-(methyl-(5-methyl-2-phenyl-thiazol-4-ylmethyl)-amino]-cyclohexyl}-3H-benzoxazol-2-one.
- 20. The compound according to claim 10 of Formula XI
- 21. The compound according to claim 20 selected from the group consisting of:
trans-6-(4-{[3-(4-fluoro-phenyl)-4,5-dihydro-isoxazol-5-ylmethyl]-amino}-cyclohexyl)-3H-benzoxazol-2-one; and trans-6-(4-{[3-(4-fluoro-phenyl)-4,5-dihydro-isoxazol-5-ylmethyl]-methyl-amino}-cyclohexyl)-3H-benzoxazol-2-one.
- 22. The compound according to claim 10 of Formula XII
- 23. A pharmaceutical composition, comprising a therapeutically effective amount of a compound of Formula VIa, or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable diluent, carrier, or excipient.
- 24. The pharmaceutical composition according to claim 23, wherein the compound of Formula VIa, or a pharmaceutically acceptable salt thereof, is selected from the group consisting of:
trans-6-(5-{[methyl-(4-phenyl-cyclohexyl)-amino]-methyl}-4,5-dihydro-isoxazol-3-yl)-3H-benzoxazol-2-one; trans-6-{5-[4-(4-fluoro-phenyl)-cyclohexylamino]-methyl-2-oxo-oxazolidin-3-yl}-3H-benzoxazol-2-one; and trans-6-(5-{[4-(4-fluoro-phenyl)-cyclohexyl]-methyl-amino}-methyl-2-oxo-oxazolidin-3-yl)-3H-benzoxazol-2-one.
- 25. A pharmaceutical composition, comprising a therapeutically effective amount of a compound of Formula VI, or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable diluent, carrier, or excipient.
- 26. The pharmaceutical composition according to claim 25, wherein the compound of Formula VI, or a pharmaceutically acceptable salt thereof, is selected from the group consisting of:
trans-6-{4-[methyl-(2-methyl-5-phenyl-furan-3-ylmethyl)-amino]-cyclohexyl}-3H-benzoxazol-2-one; trans-(R)-6-{4-[2-oxo-3-phenyl-oxazolidin-5-ylmethyl)-amino]-cyclohexyl}-3H-benzoxazol-2-one; trans-(R)-6-{4-[methyl-(2-oxo-3-phenyl-oxazolidin-5-ylmethyl)-amino]-cyclohexyl}-3H-benzoxazol-2-one; trans-6-{4-[(5-methyl-2-phenyl-thiazol-4-ylmethyl)-amino]-cyclohexyl}-3H-benzoxazol-2-one; trans-6-{4-[methyl-(5-methyl-2-phenyl-thiazol-4-ylmethyl)-amino]-cyclohexyl}-3H-benzoxazol-2-one; trans-6-(4-{[3-(4-Fluoro-phenyl)-4,5-dihydro-isoxazol-5-ylmethyl]-amino}-cyclohexyl)-3H-benzoxazol-2-one; and trans-6-(4-{[3-(4-Fluoro-phenyl)-4,5-dihydro-isoxazol-5-ylmethyl]-methyl-amino}-cyclohexyl)-3H-benzoxazol-2-one.
- 27. A method of treating disorders responsive to the selective blockade of the N-methyl-D-aspartate receptor subtypes in a subject, suffering therefrom, which comprises administering a therapeutically effective amount of a compound according to claim 1.
- 28. The method according to claim 27, wherein the disorder being treated is selected from stroke, cerebral ischemia, depression, trauma, hypoglycemia, anxiety, migraine headache, convulsions, aminoglycoside antibiotics-induced hearing loss, psychosis, glaucoma, CMV retinitis, opioid tolerance or withdrawal, pain, including chronic pain, neuropathic pain, or surgical pain, and urinary incontinence.
- 29. The method according to claim 27 wherein the disorder being treated is pain.
- 30. The method according to claim 27, wherein the disorder being treated is Parkinson's disease.
- 31. The method according to claim 27, wherein the compound of Formula I, or a pharmaceutically acceptable salt thereof, is selected from the group consisting of:
trans-6-(5-{[methyl-(4-phenyl-cyclohexyl)-amino]-methyl}-4,5-dihydro-isoxazol-3-yl)-3H-benzoxazol-2-one; trans-6-{5-[4-(4-fluoro-phenyl)-cyclohexylamino]-methyl-2-oxo-oxazolidin-3-yl}-3H-benzoxazol-2-one; and trans-6-(5-{[4-(4-fluoro-phenyl)-cyclohexyl]-methyl-amino}-methyl-2-oxo-oxazolidin-3-yl)-3H-benzoxazol-2-one.
- 32. The method according to claim 27, further comprising administering a dopamine agonist.
- 33. The method according to claim 27, further comprising administering a dopamine agonist wherein said dopamine agonist is L-DOPA.
- 34. A method of treating disorders responsive to the selective blockade of the N-methyl-D-aspartate receptor subtypes in a subject, suffering therefrom, which comprises administering a therapeutically effective amount of a compound according to claim 10.
- 35. The method according to claim 34, wherein the disorder being treated is selected from stroke, cerebral ischemia, depression, trauma, hypoglycemia, anxiety, migraine headache, convulsions, aminoglycoside antibiotics-induced hearing loss, psychosis, glaucoma, CMV retinitis, opioid tolerance or withdrawal, pain, including chronic pain, neuropathic pain, or surgical pain, and urinary incontinence.
- 36. The method according to claim 34, wherein the disorder being treated is pain.
- 37. The method according to claim 34, wherein the disorder being treated is Parkinson's disease.
- 38. The method according to claim 34, wherein the compound of Formula VI, or a pharmaceutically acceptable salt thereof, is selected from the group consisting of:
trans-6-{4-[Methyl-(2-methyl-5-phenyl-furan-3-ylmethyl)-amino]-cyclohexyl}-3H-benzoxazol-2-one; trans-(R)-6-{4-[2-Oxo-3-phenyl-oxazolidin-5-ylmethyl)-amino]-cyclohexyl}-3H-benzoxazol-2-one; trans-(R)-6-{4-[Methyl-(2-oxo-3-phenyl-oxazolidin-5-ylmethyl)-amino]-cyclohexyl}-3H-benzoxazol-2-one; trans-6-{4-[(5-Methyl-2-phenyl-thiazol-4-ylmethyl)-amino]-cyclohexyl}-3H-benzoxazol-2-one; trans-6-{4-[Methyl-(5-methyl-2-phenyl-thiazol-4-ylmethyl)-amino]-cyclohexyl}-3H-benzoxazol-2-one; trans-6-(4-{[3-(4-Fluoro-phenyl)-4,5-dihydro-isoxazol-5-ylmethyl]-amino}-cyclohexyl)-3H-benzoxazol-2-one; and trans-6-(4-{[3-(4-Fluoro-phenyl)-4,5-dihydro-isoxazol-5-ylmethyl]-methyl-amino}-cyclohexyl)-3H-benzoxazol-2-one.
- 39. The method according to claim 34, further comprising administering a dopamine agonist.
- 40. The method according to claim 34, further comprising administering a dopamine agonist wherein said dopamine agonist is L-DOPA.
- 41. A compound selected from the group consisting of:
6-(cyclohexanone-4-yl)benzoxazolin-2-one; 3-(3-benzyloxy-4-nitro-phenyl)-5-[methyl-(4-phenyl-cyclohexyl)-amino]methyl-4,5-dihydro-isoxazole; 3-(4-amino-3-hydroxy-phenyl)-5-[methyl-(4-phenyl-cyclohexyl)-amino]methyl-4,5-dihydro-isoxazole; 3-(methylamino)methyl-2-methyl-5-phenyl-furan; 5-(aminomethyl)-3-phenyl-2-oxo-oxazolidine; 6-[5-(aminomethyl)-2-oxo-oxazolidin-3-yl]-3H-benzoxazol-2-one; 4-(aminomethyl)-5-methyl-2-phenyl-thiazole; and 5-(aminomethyl)-3-(4-fluorophenyl)-4,5-dihydro-isoxazole.
- 42. A method of preparing compounds of Formula VIa
- 43. A method of preparing a compound of Formula VI
Parent Case Info
[0001] This application claims priority to U.S. serial No. 60/279,169, filed Mar. 27, 2001, the entire contents of which are herein incorporated by reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60279169 |
Mar 2001 |
US |