US 2003/0125352 A1 · Therapeutic tropane compounds

Abstract

This invention relates to therapeutic uses of boat tropane analogs, e.g, treatment of neurodegenerative disorders. More specifically the invention relates to a method of treating a neurological disorder in patient comprising administering to the patient an effective amount of a boat tropane compound.

Claims22

Dependent claims

A method of treating a neurological disorder in a patient comprising administering to the patient an effective amount of a boat tropane compound.

A method of treating a neurodegenerative disease in a patient comprising administering to the patient an effective amount of a boat tropane compound selected from the following compounds:

2β-(1-Propanoyl)-3α-(4-fluorophenyl)-tropane;
2β-(1-Propanoyl)-3α-(3,4-dichlorophenyl)tropane;
1-{3α-(3,4-Dichlorophenyl)-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}oct-2-yl}propan-1-one;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-6β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(2-naphthyl)-6β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(4-fluorophenyl)-6β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-phenyl-6β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
(1S)-2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
(1R)-2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(2-naphthyl)-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(4-fluorophenyl)-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-phenyl-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-7α-benzoyloxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-6α-benzoyloxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-7α-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-6α-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-8-methyl-8-azabicyclo{3.2.1}oct-7-one;
2β-Carbomethoxy-3β-(3,4-dichlorophenyl)-8-methyl-8-azabicyclo{3.2.1}oct-7-one;
2β-Carbomethoxy-3α-bis(fluorophenyl)methoxy-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
and
2β-Carbomethoxy-3α-bis(4-fluorophenyl)methoxy-6β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane.

19 more elements

A method for treating psychiatric dysfunction in a mammal comprising administering to the mammal an effective amount of a boat tropane compound selected from the following compounds:

2β-(1-Propanoyl)-3α-(4-fluorophenyl)-tropane;
2β-(1-Propanoyl)-3α-(3,4-dichlorophenyl)tropane;
1-{3α-(3,4-Dichlorophenyl)-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}oct-2-yl}propan-1-one;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-6β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(2-naphthyl)-6β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(4-fluorophenyl)-6β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-phenyl-6β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
(1S)-2β-Carbomethoxy-3β-(3,4-dichlorophenyl)-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
(1R)-2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(2-naphthyl)-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(4-fluorophenyl)-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-phenyl-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-7α-benzoyloxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-6α-benzoyloxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-7α-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-6α-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-8-methyl-8-azabicyclo{3.2.1}oct-7-one;
2β-Carbomethoxy-3β-(3,4-dichlorophenyl)-8-methyl-8-azabicyclo{3.2.1}oct-7-one;
2β-Carbomethoxy-3α-bis(fluorophenyl)methoxy-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
and
2β-Carbomethoxy-3α-bis(4-fluorophenyl)methoxy-6β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane.

19 more elements

A method for treating dopamine related dysfunction in a mammal comprising administering to the mammal a dopamine reuptake inhibiting amount of a compound selected from the following compounds:

2β-(1-Propanoyl)-3α-(4-fluorophenyl)-tropane;
2β-(1-Propanoyl)-3α-(3,4-dichlorophenyl)tropane;
1-{3α-(3,4-Dichlorophenyl)-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}oct-2-yl}propan-1-one;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-6β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(2-naphthyl)-6β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(4-fluorophenyl)-6β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-phenyl-6β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
(1S)-2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
(1R)-2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(2-naphthyl)-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(4-fluorophenyl)-762 -hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-phenyl-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-7α-benzoyloxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-6α-benzoyloxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-7α-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-6α-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-8-methyl-8-azabicyclo{3.2.1}oct-7-one;
2β-Carbomethoxy-3β-(3,4-dichlorophenyl)-8-methyl-8-azabicyclo{3.2.1}oct-7-one;
2β-Carbomethoxy-3α-bis(fluorophenyl)methoxy-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
and
2β-Carbomethoxy-3α-bis(4-fluorophenyl)methoxy-6β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane.

19 more elements

A method for treating clinical dysfunction in a mammal comprising administering to the mammal an effective amount of a compound selected from the following compounds:

2β-(1-Propanoyl)-3α-(4-fluorophenyl)-tropane;
2β-(1-Propanoyl)-3α-(3,4-dichlorophenyl)tropane;
1-{3α-(3,4-Dichlorophenyl)-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}oct-2-yl}propan-1-one;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-6β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(2-naphthyl)-6β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(4-fluorophenyl)-6 β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-phenyl-6β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
(1S)-2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
(1R)-2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(2-naphthyl)-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(4-fluorophenyl)-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-phenyl-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-7α-benzoyloxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-6α-benzoyloxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-7α-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-6α-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
2β-Carbomethoxy-3α-(3,4-dichlorophenyl)-8-methyl-8-azabicyclo{3.2.1}oct-7-one;
2β-Carbomethoxy-3β-(3,4-dichlorophenyl)-8-methyl-8-azabicyclo{3.2.1}oct-7-one;
2β-Carbomethoxy-3α-bis(fluorophenyl)methoxy-7β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane;
and
2β-Carbomethoxy-3α-bis(4-fluorophenyl)methoxy-6β-hydroxy-8-methyl-8-azabicyclo{3.2.1}octane.

19 more elements

Dependencies are inferred from the claim text.

Facts

Application

10/222,530Filed 16 Aug 2002

Priority

17 Aug 2001

Published

3 Jul 2003

Term ends

Not estimatedThe source records don’t support an estimate.

Classification9 codes

A61K 31/439
Having six-membered rings with one nitrogen as the only ring hetero atom: the ring forming part of a bridged ring system, e.g. quinuclidine
A61K 31/46
Having six-membered rings with one nitrogen as the only ring hetero atom: 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
A61P 25/00
Drugs for disorders of the nervous system
A61P 25/06
Drugs for disorders of the nervous system: antimigraine agents

Therapeutic tropane compounds

Life of this patent

Abstract

Claims22

Therapeutic tropane compounds

Life of this patent

Abstract

Claims22