Claims
- 1. A compound represented by the formula: ##STR10## in which: X is H, Cl, Br, F, I, CF.sub.3, C.sub.1-6 alkyl, COR.sup.10, CO.sub.2 R.sup.10, CONR.sup.16 R.sup.11, CN, NO.sub.2, NR.sup.12 R.sup.13, OR.sup.12, SC.sub.1-4 alkyl, S(CH.sub.2).sub.0-6 PH, SCF.sub.3, or any accessible combination thereof of up to three substituents;
- R is H, C.sub.1-6 alkyl, or C.sub.3-5 alkenyl;
- R.sup.1 is W, (CH.sub.2).sub.0-2 CWYZ, or C.sub.3-5 alkenyl, except where the double bond is in the 1-position;
- R.sup.10 is C.sub.1-6 alkyl or (CH.sub.2).sub.0-6 PH;
- R.sup.11 and R.sup.16 independently are H, C.sub.1-6 alkyl, or (CH.sub.2).sub.0-6 PH;
- R.sup.12 is H, C.sub.1-6 alkyl, COR.sup.14, or SO.sub.2 R.sup.15 ;
- each R.sup.13 independently is H or C.sub.1-6 alkyl;
- R.sup.14 and R.sup.15 independently are C.sub.1-6 alkyl or (CH.sub.2).sub.0-6 PH;
- W is H, NO.sub.2, C.sub.1-6 alkyl, CH.sub.2 CH.sub.2 OH, CN, C(R.sup.13).sub.2 (OR.sup.2), CH.sub.2 SR.sup.2, COR.sup.2, CO.sub.2 R.sup.2, CONR.sup.3 R.sup.4, SO.sub.2 NR.sup.3 R.sup.4, SO.sub.3 R.sup.2, SO.sub.2 R.sup.5, SOR.sup.5, SR.sup.5, P(O)(OR.sup.3)(OR.sup.4), P(O)R.sup.5 (OR.sup.3), P(O)R.sup.5 R.sup.6, P(O)(OR.sup.2)NR.sup.3 R.sup.4, P(O)(NR.sup.3 R.sup.4).sub.2, P(O)R.sup.5 (NR.sup.3 R.sup.4), Cl, Br, F, I, CF.sub.3, or (CH.sub.2).sub.0-6 PH;
- Y and Z independently are H or C.sub.1-6 alkyl;
- R.sup.2, R.sup.3, and R.sup.4 independently are H, C.sub.1-6 alkyl, C.sub.3-5 alkenyl, or (CH.sub.2).sub.0-6 PH; and
- R.sup.5 and R.sup.6 independently are C.sub.1-6 alkyl, C.sub.3-5 alkenyl, or (CH.sub.2).sub.0-6 PH; where pH represents unsubstituted phenyl or phenyl substituted by up to three substituents selected from C.sub.1-6 alkyl, C.sub.1-6 alkoxy, halo, CF.sub.3 or CN; or a pharmaceutically acceptable salt thereof.
- 2. A compound represented by the formula: ##STR11## in which: X is H, Cl, Br, F, I, CF.sub.3, C.sub.1-6 alkyl, COR.sup.10, CO.sub.2 R.sup.10, CONR.sup.16 R.sup.11, CN, NO.sub.2, NR.sup.12 R.sup.13, OR.sup.12, SC.sub.1-4 alkyl, S(CH.sub.2).sub.0-6 PH, or SCF.sub.3 ;
- R is H, C.sub.1-6 alkyl, or C.sub.3-5 alkenyl;
- R.sup.1 is W, (CH.sub.2).sub.0-2 CWYZ, or C.sub.3-5 alkenyl, except where the double bond is in the 1-position;
- R.sup.10 is C.sub.1-6 alkyl or (CH.sub.2).sub.0-6 PH;
- R.sup.11 and R.sup.16 independently are H, C.sub.1-6 alkyl, or (CH.sub.2).sub.0-6 PH;
- R.sup.12 is H, C.sub.1-6 alkyl, COR.sup.14, or SO.sub.2 R.sup.15 ;
- each R.sup.13 independently is H or C.sub.1-6 alkyl;
- R.sup.14 and R.sup.15 independently are C.sub.1-6 alkyl or (CH.sub.2).sub.0-6 PH;
- W is H, NO.sub.2, C.sub.1-6 alkyl, CH.sub.2 CH.sub.2 OH, CN, C(R.sup.13).sub.2 (OR.sup.2), CH.sub.2 SR.sup.2, COR.sup.2, CO.sub.2 R.sup.2, CONR.sup.3 R.sup.4, SO.sub.2 NR.sup.3 R.sup.4, SO.sub.3 R.sup.2, SO.sub.2 R.sup.5, SOR.sup.5, SR.sup.5, P(O)(OR.sup.3)(OR.sup.4), P(O)R.sup.5 (OR.sup.3), P(O)R.sup.5 R.sup.6, P(O)(OR.sup.2)NR.sup.3 R.sup.4, P(O)(NR.sup.3 R.sup.4).sub.2, P(O)R.sup.5 (NR.sup.3 R.sup.4), Cl, Br, F, I, CF.sub.3, or (CH.sub.2).sub.0-6 PH;
- Y and Z independently are H or C.sub.1-6 alkyl;
- R.sup.2, R.sup.3, and R.sup.4 independently are H, C.sub.1-6 alkyl, C.sub.3-5 alkenyl, or (CH.sub.2).sub.0-6 PH; where pH represents unsubstituted phenyl or phenyl substituted by up to three substituents selected from C.sub.1-6 alkyl, C.sub.1-6 alkoxy, halo, CF.sub.3 or CN; and
- R.sup.5 and R.sup.6 independently are C.sub.1-6 alkyl, C.sub.3-5 alkenyl, or (CH.sub.2).sub.0-6 PH; or a pharmaceutically acceptable salt thereof.
- 3. A compound of claim 1 wherein X is one or two substituents selected from the group consisting of Cl, Br, F, I, CN, or NR.sup.12 R.sup.13.
- 4. A compound of claim 3 wherein R is CH.sub.3 or H, and X is at position 7 or 7,9.
- 5. A compound of claim 4 that is 7-chloro-3,4,5,6-tetrahydro-2,4-dimethylfuro[4,3,2-ef][3]benzazepine, or a pharmaceutically acceptable salt thereof.
- 6. A compound of claim 4 that is 2-bromo-7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine, or a pharmaceutically acceptable salt thereof.
- 7. A compound of claim 4 that is:
- ethyl 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxylate;
- 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-methanol
- 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxaldehyde;
- methyl 7-chloro-3,4,5,6 tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxylate;
- 2-propenyl-7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxylate;
- 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carbonitrile;
- 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine;
- 7-chloro-2-ethyl-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine;
- ethyl 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-propanoate;
- 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-propanol;
- 7-chloro-3,4,5,6-tetrahydro-4-methyl-2-[(2-propenyloxy)methyl]furo[4,3,2-ef][3]benzazepine;
- 7-chloro-3,4,5,6-tetrahydro-4-methyl-2-[(propyloxy)methyl]furo[4,3,2-ef][3]benzazepine;
- 7-chloro-3,4,5,6-tetrahydro-4-methyl-2-[(3-methyl-2-butenyloxy)methyl]furo[4,3,2-ef][3]benzazepine;
- 7-chloro-3,4,5,6-tetrahydro-4-methyl-2-[(2-propenylthio)methyl]furo[4,3,2-ef][3]benzazepine;
- 7-chloro-3,4,5,6-tetrahydro-4-methyl-2-(trifluoromethyl)furo[4,3,2-ef][3]benzazepine;
- 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxamide;
- N-butyl-7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxamide;
- N,N-dimethyl-7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxamide;
- 7-chloro-3,4,5,6-tetrahydro-4-methyl-N-(phenylmethyl)furo[4,3,2-ef][3]benzazepine-2-carboxamide;
- 7-chloro-3,4,5,6-tetrahydro-4-methyl-N-(2-phenylethyl)furo[4,3,2-ef][3]benzazepine-2-carboxamide;
- 7-chloro-3,4,5,6-tetrahydro-N,4-dimethyl-N-(2-phenylethyl)furo[4,3,2-ef][3]benzazepine-2-carboxamide;
- 7-chloro-3,4,5,6-tetrahydro-4-methyl-N-(3-phenylpropyl)furo[4,3,2-ef][3]benzazepine-2-carboxamide;
- phenylmethyl-7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-propanoate;
- 2,7-dichloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine;
- 7-chloro-2-[(4-chlorophenyl)methyloxy]-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine;
- 7-fluoro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-methanol;
- 7-chloro-9-dimethylamino-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-methanol;
- 7-bromo-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-methanol;
- 7-dimethylamino-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-methanol;
- ethyl 7-cyano-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxylate;
- ethyl 7-chloro-9-dimethylamino-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxylate;
- ethyl 7-chloro-9-methylamino-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxylate;
- ethyl 7,9-dichloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxylate; or
- ethyl 7-dimethylamino-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxylate;
- or a pharmaceutically acceptable salt thereof.
- 8. A pharmaceutical composition comprising a compound of claim 1 and a suitable pharmaceutical carrier.
- 9. A pharmaceutical composition of claim 8 wherein the compound is 7-chloro-3,4,5,6-tetrahydro-2,4-dimethylfuro[4,3,2-ef][3]benzazepine.
- 10. A pharmaceutical composition of claim 8 wherein the compound is 2-bromo-7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine.
- 11. A pharmaceutical composition of claim 9 wherein the compound is:
- ethyl 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxylate;
- 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-methanol;
- 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxaldehyde;
- methyl 7-chloro-3,4,5,6 tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxylate;
- methyl 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxylate;
- 2-propenyl-7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxylate;
- 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carbonitrile;
- 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine;
- 7-chloro-2-ethyl-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine;
- ethyl 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-propanoate;
- 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-propanol;
- 7-chloro-3,4,5,6-tetrahydro-4-methyl-2-[(2-propenyloxy)methyl]furo[4,3,2-ef][3]benzazepine;
- 7-chloro-3,4,5,6-tetrahydro-4-methyl-2-[(propyloxy)methyl]furo[4,3,2-ef][3]benzazepine;
- 7-chloro-3,4,5,6-tetrahydro-4-methyl-2-[(3-methyl-2-butenyloxy)methyl]furo[4,3,2-ef][3]benzazepine;
- 7-chloro-3,4,5,6-tetrahydro-4-methyl-2-[(2-propenylthio)methyl]furo[4,3,2-ef][3]benzazepine;
- 7-chloro-3,4,5,6-tetrahydro-4-methyl-2-(trifluoromethyl)furo[4,3,2-ef][3]benzazepine;
- 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxamide;
- N-butyl-7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxamide;
- N,N-dimethyl-7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxamide;
- 7-chloro-3,4,5,6-tetrahydro-4-methyl-N-(phenylmethyl)furo[4,3,2-ef][3]benzazepine-2-carboxamide;
- 7-chloro-3,4,5,6-tetrahydro-4-methyl-N-(2-phenylethyl)furo[4,3,2-ef][3]benzazepine-2-carboxamide;
- 7-chloro-3,4,5,6-tetrahydro-N,4-dimethyl-N-(2-phenylethyl)furo[4,3,2-ef][3]benzazepine-2-carboxamide;
- 7-chloro-3,4,5,6-tetrahydro-4-methyl-N-(3-phenylpropyl)furo[4,3,2-ef][3]benzazepine-2-carboxamide;
- phenylmethyl 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-propanoate;
- 2,7-dichloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine;
- 7-chloro-2-[(4-chlorophenyl)methyloxy]-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine;
- 7-fluoro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-methanol;
- 7-chloro-9-dimethylamino-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-methanol;
- 7-bromo-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-methanol;
- 7-dimethylamino-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-methanol;
- ethyl 7-cyano-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxylate;
- ethyl 7-chloro-9-dimethylamino-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxylate;
- ethyl 7-chloro-9-methylamino-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxylate;
- ethyl 7,9-dichloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxylate; or
- ethyl 7-dimethylamino-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxylate.
- 12. A method of antagonizing .alpha.-adrenergic receptors in mammals that comprises administering to a subject in need thereof an effective amount of a compound of claim 1.
- 13. A method of claim 12 wherein the compound is 7-chloro-3,4,5,6-tetrahydro-2,4-dimethylfuro[4,3,2-ef][3]benzazepine.
- 14. A method of claim 12 wherein the compound is 2-bromo-7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3benzazepine.
- 15. A method of claim 12 wherein the compound is:
- ethyl 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxylate;
- 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-methanol;
- 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxaldehyde;
- methyl 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxylate;
- 2-propenyl 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxylate;
- 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carbonitrile;
- 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine;
- 7-chloro-2-ethyl-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine;
- ethyl 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-propanoate;
- 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-propanol;
- 7-chloro-3,4,5,6-tetrahydro-4-methyl-2-[(2-propenyloxy)methyl]furo[4,3,2-ef][3]benzazepine;
- 7-chloro-3,4,5,6-tetrahydro-4-methyl-2-[(propyloxy)methyl]furo[4,3,2-ef][3]benzazepine;
- 7-chloro-3,4,5,6-tetrahydro-4-methyl-2-[(3-methyl-2-butenyloxy)methyl]furo[4,3,2-ef][3]benzazepine;
- 7-chloro-3,4,5,6-tetrahydro-4-methyl-2-[(2-propenylthio)methyl]furo[4,3,2-ef][3]benzazepine;
- 7-chloro-3,4,5,6-tetrahydro-4-methyl-2-(trifluoromethyl)furo[4,3,2-ef][3]benzazepine;
- 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxamide;
- N-butyl-7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxamide;
- N,N-dimethyl-7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxamide;
- 7-chloro-3,4,5,6-tetrahydro-4-methyl-N-(phenylmethl)furo[4,3,2-ef][3]benzazepine-2-carboxamide;
- 7-chloro-3,4,5,6-tetrahydro-4-methyl-N-(2-phenylethyl)furo[4,3,2-ef][3]benzazepine-2-carboxamide;
- 7-chloro-3,4,5,6-tetrahydro-N,4-dimethyl-N-(2-phenylethyl)furo[4,3,2-ef][3]benzazepine-2-carboxamide;
- 7-chloro-3,4,5,6-tetrahydro-4-methyl-N-(3-phenylpropyl)furo[4,3,2-ef][3]benzazepine-2-carboxamide;
- phenylmethyl 7-chloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-propanoate;
- 2. 7-dichloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine;
- 7-chloro-2-[(4-chlorophenyl)methyloxy]-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine;
- 7-fluoro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-methanol;
- 7-chloro-9-dimethylamino-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-methanol;
- 7-bromo-3,4,5,6-tetrahydro-4-methylfuro-[4,3,2-ef][3]benzazepine-2-methanol;
- 7-dimethylamino-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-methanol;
- ethyl 7-cyano-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxylate;
- ethyl 7-chloro-9-dimethylamino-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxylate;
- ethyl 7-chloro-9-methylamino-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxylate;
- ethyl 7,9-dichloro-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxylate; or
- ethyl 7-dimethylamino-3,4,5,6-tetrahydro-4-methylfuro[4,3,2-ef][3]benzazepine-2-carboxylate.
- 16. A method of reducing blood pressure in mammals that comprises administering to a subject in need thereof an effective amount of a compound of claim 1.
- 17. A method of treating peripheral vascular diseases in mammals that comprises administering to a subject in need thereof an effective amount of a compound of claim 1.
- 18. A method of treating benign prostatic hyperthrophy in mammals that comprises administering to a subject in need thereof an effective amount of a compound of claim 1.
- 19. A method of treating congestive heart failure in mammals that comprises administering to a subject in need thereof an effective amount of a compound of claim 1.
REFERENCE TO EARLIER APPLICATION
This application is a continuation-in-part of application Ser. No. 07/200,816, filed June 1, 1988, now abandoned.
US Referenced Citations (4)
Foreign Referenced Citations (1)
Number |
Date |
Country |
WO8700522 |
Jan 1987 |
WOX |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
200816 |
Jun 1988 |
|