Claims
- 1. A compound having the formula: ##STR124## wherein A is O,
- n is 0 or 1;
- R is hydrogen, lower alkyl or a prodrug ester group;
- R.sub.1 is selected from hydrogen, halogen, lower alkyl, C.sub.1 -C.sub.6 haloalkyl and lower alkoxy;
- R.sub.2 is selected from hydrogen, halogen, lower alkyl, and C.sub.1 -C.sub.6 haloalkyl or, taken together with R.sub.8 forms a saturated fused ring of from six or seven carbon atoms;
- R.sub.3 is selected from
- hydrogen,
- alkyl of from one to twelve carbon atoms,
- alkenyl of from two to twelve carbon atoms,
- alkynyl of from two to twelve carbon atoms,
- cycloalkyl of from three to twelve carbon atoms,
- aryl wherein aryl is selected from phenyl, 1 - or 2-naphthyl, pyridyl, pyrazinyl, thiazolyl, furyl, and thienyl, optionally substituted by hydroxy, halogen, lower alkyl or lower alkoxy,
- arylalkyl wherein the aryl portion is as defined above and the alkyl portion is of from one to twelve carbon atoms or,
- R.sub.3, taken together with R.sub.4 forms a saturated spiroalkyl group of from five to seven carbon atoms or,
- R.sub.3, taken together with R.sub.5, forms a saturated fused cycloalkyl ring of six carbon atoms;
- R.sub.4 is hydrogen or alkyl of from one to twelve carbon atoms;
- R.sub.5 is hydrogen or alkyl of from one to twelve carbon atoms;
- R.sub.6 is selected from hydrogen,
- alkyl of from one to twelve carbon atoms,
- alkenyl of from one to twelve carbon atoms,
- alkynyl of from two to twelve carbon atoms,
- cycloalkyl of from three to twelve carbon atoms, and
- aralkyl, wherein aralkyl is as defined above, or
- taken together with R.sub.7 or R.sub.8 forms a saturated nitrogen-containing heterocycle of from five to seven ring atoms;
- R.sub.7 is hydrogen or alkyl of from one to twelve carbon atoms or, taken together with R.sub.6 or R.sub.8 forms a saturated nitrogen-containing heterocycle of from five to seven ring atoms;
- R.sub.8 is hydrogen or alkyl of from one to twelve carbon atoms or, taken together with R.sub.6 or R.sub.7, forms a saturated nitrogen-containing heterocycle of from five to seven ring atoms, or, or
- a pharaceutically acceptable salt, ester, or amide thereof;
- subject to the proviso that R.sub.3 and R.sub.4 cannot simultaneously both be hydrogen.
- 2. A compound according to claim 1 in which R.sub.3 is aryl, alkyl or cycloalkyl.
- 3. A compound according to claim 1 in which R.sub.3 is phenyl or cyclohexyl.
- 4. A compound according to claim 1 in which n=0, R.sub.8 is hydrogen and NR.sub.6 R.sub.7 is NH.sub.2 or NHCH.sub.3.
- 5. A compound according to claim 1 in which R.sub.1 is methyl or bromo.
- 6. A compound according to claim 1 in which R is hydrogen or a readily cleavable group.
- 7. A compound according to claim 1 in which n is 0; R is hydrogen or a readily cleavable group; R.sub.2 is hydrogen or taken together with R.sub.8 forms a fused ring; R.sub.4 is hydrogen and R.sub.5 is hydrogen.
- 8. A compound selected from the group consisting of:
- [1R,3S]-1-aminomethyl-3-cyclohexyl-3,4-dihydro-5-hydroxy-6-methyl-1H-2-benzopyran;
- [1R,3S]-1-(N,N-dimethylamino)methyl-3-cyclohexyl-3,4-dihydro-5-hydroxy-6-methyl -1H-2-benzopyran;
- [1R,3S]-1-(N-methylamino)methyl-3-cyclohexyl-3,4-dihydro-5-hydroxy-6-methyl-1H-2-benzopyran;
- [1R,3S]-1-aminomethyl-6-bromo-3,4-dihydro-5-hydroxy-3-phenyl-1H-2-benzopyran;
- [1R,3R]-1-aminomethyl-6-bromo-3,4-dihydro-5-hydroxy-3-phenyl-1H-2-benzopyran;
- [1R,3S]-1-aminomethyl-3,4-dihydro-5-hydroxy-3-phenyl-1H-2-benzopyran;
- [1R,3R]-1-(N-methylamino)methyl-6-bromo-3,4-dihydro-5-hydroxy-3-phenyl-1H-2-benzopyran;
- [1R,3S]-1-aminomethyl-3,4-dihydro-5,6-dimethoxy-3-phenyl-1H-2-benzopyran; and
- [1R,3S]-1-aminomethyl-3,4-dihydro-5-hydroxy-6-methoxy-3-phenyl-1H-2-benzopyran;
- or a pharmaceutically acceptable salt, ester, or amide thereof.
- 9. A pharmaceutical composition for selectively acting on dopaminergic receptors comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound as defined by claim 1.
- 10. A pharmaceutical composition for treating dopamine-related neurological disorders comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound as defined by claim 1.
- 11. A pharmaceutical composition for treating dopamine-related cardiovascular disorders comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound as defined by claim 1.
- 12. A pharmaceutical composition for treating addictive behavior disorders comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound as defined by claim 1.
- 13. A method for selectively acting on dopaminergic receptors comprising administering to a patient in need, a therapeutically effective amount of a compound as defined by claim 1.
- 14. A method for treating dopamine-related neurological disorders characterized by abnormal dopaminergic activity comprising administering to a patient in need a therapeutically acceptable amount of a compound as defined by claim 1.
- 15. A method for treating dopamine-related cardiovascular disorders comprising administering to a patient in need a therapeutically effective amount of a compound as defined by claim 1.
- 16. A method for treating addictive behavior disorders comprising administering to a patient in need a therapeutically effective amount of a compound as defined by claim 1.
Parent Case Info
This application is a continuation-in-part of copending U.S. application Ser. No. 359,448, filed May 31, 1989 now U.S. Pat. No. 4963568.
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
359448 |
May 1989 |
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