Spiro-Azabicyclic Compounds useful in therapy

• US 5,902,814 A
• Filed: 09/18/1995
• Issued: 05/11/1999
• Est. Priority Date: 08/24/1994
• Status: Expired due to Fees

• Current Assignee: Astra AB (Astrazeneca PLC)
• Original Assignee: Astra AB (Astrazeneca PLC)
• Inventors: Balestra, Michael, Griffith, Ronald Conrad, Murray, Robert John, Gordon, John Charles
• Primary Examiner(s): Berch, Mark L.
• Application Number:
  US08/525,575
• Time in Patent Office: 1,331 Days
• Field of Search: 546/18, 514/278, 548/216, 548/512
• US Class Current: 514/278
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/26 Psychostimulants, e.g. nicotine, cocaine
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 453/02 containing not further condensed quinuclidine ring systems
• CPC Class Codes: C07D 487/08 Bridged systems

Abstract

There are provided new compounds of formula I: ##STR1## wherein R represents hydrogen or methyl; and

n represents 1 or 2;

or a pharmaceutically acceptable acid addition salt thereof, together with processes for preparing them, compositions containing them and their use in therapy. Compounds of formula I are expected to be useful in the treatment of psychotic disorders, intellectual impairment disorders and anxiety.

Claims

1. A compound of formula I:

##STR9## wherein R represents hydrogen or methyl; and

n represents 1 or 2;

or a pharmaceutically acceptable acid addition salt or enantiomer thereof.

2. A compound according to claim 1 wherein R represents hydrogen, or a pharmaceutically acceptable acid addition salt or enantiomer thereof.

8. A pharmaceutical formulation including a compound as defined in any one of claims 1 to 7, or a pharmaceutically acceptable acid addition salt or enantiomer thereof, in admixture with a pharmaceutically acceptable diluent or carrier.

9. A method of treatment or prophylaxis of attention deficit hyperactivity disorder, which comprises administering a therapeutically effective amount of a compound as defined in any one of claims 1 to 7, or a pharmaceutically acceptable acid addition salt or enantiomer thereof, to a patient.

10. A method of treatment or prophylaxis of anxiety, which comprises administering is a therapeutically effective amount of a compound as defined in any one of claims 1 to 7, or a pharmaceutically acceptable acid addition salt or enantiomer thereof, to a patient.

11. A process for preparation of a compound of formula I, as defined in claim 1, or a pharmaceutically acceptable acid addition salt or enantiomer thereof, which comprises:

(a) preparing a compound of formula I in which R represents hydrogen by cyclising a corresponding compound of formula II ##STR10## wherein n is as defined in claim 1;

(b) preparing a compound of formula I by reacting a corresponding compound of formula III ##STR11## wherein n and R are as defined in claim 1, with a carbonylating agents;

(c) preparing a compound of formula I in which R represents methyl by alkylating a corresponding compound of formula I in which R represents hydrogen;

or

(d) preparing one enantiomer of a compound of formula I by resolving the one enantiomer from a mixture of enantiomers;

and where desired or necessary converting the resultant compound of formula I, or an acid addition salt or enantiomer thereof, to a pharmaceutically acceptable acid addition salt or enantiomer thereof, or vice versa.

13. A method of treatment or prophylaxis of schizophrenia, which comprises administering a therapeutically effective amount of a compound as defined in any one of claims 1 to 7, or a pharmaceutically acceptable acid addition salt or enantiomer thereof, to a patient.

3. Spiro 1-azabicyclo 2.2.2!octane-3,5'"'"'-oxazolidine!-2'"'"'-one, or a pharmaceutically acceptable acid addition salt or enantiomer thereof.

4. (+)-Spiro 1-azabicyclo 2.2.2!octane-3,5'"'"'-oxazolidine!-2'"'"'-one, or a pharmaceutically acceptable acid addition salt thereof.

5. (-)-Spiro 1-azabicyclo 2.2.2!octane-3,5'"'"'-oxazolidine!-2'"'"'-one, or a pharmaceutically acceptable acid addition salt thereof.

6. Spiro 1-azabicyclo 2.2.1!heptan-3,5'"'"'-oxazolidin-2'"'"'-one!, or a pharmaceutically acceptable acid addition salt or enantiomer thereof.

7. 3'"'"'-Methyl spiro- 1-azabicyclo 2.2.2!octan-3,5'"'"'-oxazolidin-2'"'"'-one!, or a pharmaceutically acceptable acid addition salt or enantiomer thereof.

12. A compound of formula IV ##STR12## wherein n is 1 or 2, or a salt or enantiomer thereof.

14. A compound of formula III ##STR13## wherein n is 1 or 2 and R represents methyl, or a salt or enantiomer thereof.