Medicament compositions derived from quinolizine and quinolizinone and methods of use thereof
AssigneeMerrell Dow Pharmaceuticals Inc.
InventorsMaurice W. Gittos, Francis P. Miller, Stephen M. Sorensen, John R. Fozard, Paul Moser, Michael G. Palfreyman, Hsien Cheng
Life of this patent
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Abstract
The present invention is directed to the use of esters of hexahydro-8-hydroxy-2,6-methano-2H-quinolizin-3(4H)-one and hexahydro-8-hydroxy-2,6-methano-2H-quinolizines in the manufacture of a medicament for the treatment of anxiety, psychosis, glaucoma and for the stimulation of gastric motility.
Claims15
A pharmaceutical composition suitable for use in the treatment of anxiety, psychosis, glaucoma, and for stimulating gastric motility comprising a pharmaceutically acceptable carrier in admixture with a compound of the formula ##STR7## wherein A is H.sub.2, O, (H)(OH), (OH).sub.2 or N--OH;
- B is H.sub.2, (H)(CH.sub.3), (H)(CH.sub.2 NR.sub.3 R.sub.4) or CH.sub.2 wherein R.sub.3 and R.sub.4 are C.sub.2-4 alkyl or are combined to give tetramethylene, pentamethylene or --CH.sub.2 CH.sub.2 --O--CH.sub.2 CH.sub.2 ;
- R.sub.1 is ##STR8## wherein Z is NR.sub.9, O or S;
- R.sub.5, R.sub.6 and R.sub.8 are each hydrogen, halogen, C.sub.1-3 alkyl or C.sub.1-3 alkoxy;
- R.sub.7 is hydrogen, amino, (C.sub.1-4 alkyl)amino, (C.sub.1-4 alkyl).sub.2 amino, alkoxy, or nitro;
- R.sub.9 is hydrogen, C.sub.1-4 alkyl or phenyl (C.sub.1-2 alkyl);
- R.sub.10 is hydrogen, halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, hydroxyl, cyano or --CONH.sub.2 ;
- R.sub.11 is hydrogen, halogen, C.sub.1-4 alkyl or phenyl;
- the wavy line indicates that the configuration of the oxygen substituent on the ring can be endo or exo;
- and the pharmaceutically acceptable acid addition and quarternary ammonium salts of the aforesaid compounds.
A method for the treatment of anxiety comprising administering to a patient in need thereof of an effective amount of a compound of the formula ##STR9## wherein A is H.sub.2, O, (H)(OH), (OH).sub.2 or N--OH;
- B is H.sub.2, (H)(CH.sub.3), (H)(CH.sub.2 NR.sub.3 R.sub.4) or CH.sub.2 wherein R.sub.3 and R.sub.4 are C.sub.2-4 alkyl or are combined to give tetramethylene, pentamethylene or --CH.sub.2 CH.sub.2 --O--CH.sub.2 CH.sub.2 --;
- R.sub.1 is ##STR10## wherein Z is NR.sub.9, O or S;
- R.sub.5, R.sub.6 and R.sub.8 are each hydrogen, halogen, C.sub.1-3 alkyl or C.sub.1-3 alkoxy;
- R.sub.7 is hydrogen, amino, (C.sub.1-4 alkyl)amino, (C.sub.1-4 alkyl).sub.2 amino, alkoxy or nitro;
- R.sub.9 is hydrogen, C.sub.1-4 alkyl or phenyl (C.sub.1-2 alkyl);
- R.sub.10 is hydrogen, halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, hydroxy, cyano or --CONH.sub.2 ;
- R.sub.11 is hydrogen, halogen, C.sub.1-4 alkyl or phenyl;
- the wavy line indicates that the configuration of the oxygen substituent on the ring can be endo or exo;
- and the pharmaceutically acceptable acid addition and quarternary ammonium salts of the aforesaid compounds.
A method for the treatment of psychosis comprising administering to a patient in need thereof an effective amount of a compound of the formula ##STR11## wherein A is H.sub.2, O, (H)(OH), (OH).sub.2 or N--OH;
- B is H.sub.2, (H)(CH.sub.3), (H)(CH.sub.2 NR.sub.3 R.sub.4) or CH.sub.2 wherein R.sub.3 and R.sub.4 are C.sub.2-4 alkyl or are combined to give tetramethylene, pentamethylene or --CH.sub.2 CH.sub.2 --O--CH.sub.2 CH.sub.2 --;
- R.sub.1 is ##STR12## wherein Z is NR.sub.9, O or S;
- R.sub.5, R.sub.6 and R.sub.8 are each hydrogen, halogen, C.sub.1-3 alkyl or C.sub.1-3 alkoxy;
- R.sub.7 is hydrogen, amino, (C.sub.1-4 alkyl)amino, (C.sub.1-4 alkyl).sub.2 amino, alkoxy or nitro;
- R.sub.9 is hydrogen, C.sub.1-4 alkyl or phenyl (C.sub.1-2 alkyl);
- R.sub.10 is hydrogen, halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, hydroxy, cyano or --CONH.sub.2 ;
- R.sub.11 is hydrogen, halogen, C.sub.1-4 alkyl or phenyl;
- the wavy line indicates that the configuration of the oxygen substituent on the ring can be endo or exo;
- and the pharmaceutically acceptable acid addition and quarternary ammonium salts of the aforesaid compounds.
A method for stimulating gastric motility comprising administering to a patient in need thereof an effective amount of a compound of the formula:
- ##STR13## wherein A is H.sub.2, O, (H)(OH), (OH).sub.2 or N--OH;
- B is H.sub.2, (H)(CH.sub.3), (H)(CH.sub.2 NH.sub.3 R.sub.4) or CH.sub.2 wherein R.sub.3 and R.sub.4 are C.sub.2-4 alkyl or are combined to give tetramethylene, pentamethylene or --CH.sub.2 CH.sub.2 --O--CH.sub.2 CH.sub.2 --;
- R.sub.1 is ##STR14## wherein Z is NR.sub.9, O or S;
- R.sub.5, R.sub.6 and R.sub.8 are each hydrogen, halogen, C.sub.1-3 alkyl or C.sub.1-3 alkoxy;
- R.sub.7 is hydrogen, amino, (C.sub.1-4 alkyl)amino, (C.sub.1-4 alkyl).sub.2 amino, alkoxy or nitro;
- R.sub.9 is hydrogen, C.sub.1-4 alkyl or phenyl (C.sub.1-2 alkyl);
- R.sub.10 is hydrogen, halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, hydroxy, cyano or --CONH.sub.2 ;
- R.sub.11 is hydrogen, halogen, C.sub.1-4 alkyl or phenyl;
- the wavy line indicates that the configuration of the oxygen substituent on the ring can be endo or exo;
- and the pharmaceutically acceptable acid addition and quarternary ammonium salts of the aforesaid compounds.
A method for the treatment of glaucoma comprising administering to a patient in need thereof an effective amount of a compound of the formula:
- ##STR15## wherein A is H.sub.2, O, (H)(OH), (OH).sub.2 or N--OH;
- B is H.sub.2, (H)(CH.sub.3), (H)(CH.sub.2 NR.sub.3 R.sub.4) or CH.sub.2 wherein R.sub.3 and R.sub.4 are C.sub.2-4 alkyl or are combined to give tetramethylene, pentamethylene or --CH.sub.2 CH.sub.2 --O--CH.sub.2 CH.sub.2 --;
- R.sub.1 is ##STR16## wherein Z is NR.sub.9, O or S;
- R.sub.5, R.sub.6 and R.sub.8 are each hydrogen, halogen, C.sub.1-3 alkyl or C.sub.1-3 alkoxy;
- R.sub.7 is hydrogen, amino, (C.sub.1-4 alkyl)amino, (C.sub.1-4 alkyl).sub.2 amino, alkoxy or nitro;
- R.sub.9 is hydrogen, C.sub.1-4 alkyl or phenyl (C.sub.1-2 alkyl);
- R.sub.10 is hydrogen, halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, hydroxy, cyano or --CONH.sub.2 ;
- R.sub.11 is hydrogen, halogen, C.sub.1.varies.4 alkyl or phenyl;
- the wavy line indicates that the configuration of the oxygen substituent on the ring can be endo or exo;
- and the pharmaceutically acceptable acid addition and quarternary ammonium salts of the aforesaid compounds.
Dependencies are inferred from the claim text.