Spiro-isoxazolidine derivatives as cholinergic agents

• US 5,073,560 A
• Filed: 07/20/1990
• Issued: 12/17/1991
• Est. Priority Date: 07/20/1990
• Status: Expired due to Fees

• Current Assignee: Astra AB (Astrazeneca PLC)
• Original Assignee: Fisons Limited (Sanofi )
• Inventors: Kover, Alexander, Wu, Edwin S.
• Primary Examiner(s): Scalzo, Catherine S. Kilby
• Application Number:
  US07/556,112
• Time in Patent Office: 515 Days
• Field of Search: 546/19, 514/278
• US Class Current: 514/278
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: C07D 498/10 Spiro-condensed systems
• CPC Class Codes: C07D 498/20 Spiro-condensed systems

Abstract

Compounds of general formula I, ##STR1## wherein: A represents (CH₂)_m optionally substituted by R₃,

B represents (CH₂)_n optionally substituted by R₄,

R₁ represents hydrogen, C₁ -C₆ alkyl, C_1-6 alkenyl or C_1-6 alkynyl,

R₂ represents hydrogen, C₁ -C₆ alkyl or COOR₅, in which R₅ represents C₁ -C₆ alkyl,

R₃ and R₄ independently represent hydrogen or C₁ -C₆ alkyl,

in addition, any two of R₂, R₃ and R₄ may together form a C_1-3 alkylene chain,

n and m independently represent an integer from 1-3 inclusive,

Y represents O or S,

and pharmaceutically acceptable acid addition salts thereof are useful as pharmaceuticals, in particular as central muscarinic acetylcholine receptor agonists. The compounds are therefore useful in the treatment of diseases such as presenile and senile dementia, Huntington'"'"'s chorea, tardive dyskinesia, hyperkinesia, mania and Tourette Syndrome.

Claims

1. A compound of formula I, ##STR7## wherein:

A represents (CH₂)_m optionally substituted by R₃,

B represents (CH₂)_n optionally substituted by R₄,

R₁ represents hydrogen, C₁ -C₆ alkyl, C_1-6 alkenyl or C_1-6 alkynyl,

R₂ represents hydrogen, C₁ -C₆ alkyl or COOR₅, in which R₅ represents C₁ -C₆ alkyl,

R₃ and R₄ independently represent hydrogen or C₁ -C₆ alkyl,

n and m independently represent an integer 2,

Y represents O or S,

and pharmaceutically acceptable acid addition salts thereof.

2. A compound according to claim 1, wherein Y represents O.

3. A compound according to claim 1, wherein R₁ and R₂ are independently represented by C_1-6 alkyl.

4. A compound according to claim 1, wherein R₁ is represented by methyl.

5. A compound according to claim 1, which is

2,8-Dimethyl-1-oxa-2,8-diazaspiro[4,5]decan-3-one

or a pharmaceutically acceptable acid addition salt thereof.

6. A compound according to claim 1 which is in the form of a pharmaceutically acceptable acid addition salt.

7. A method of treatment of a neurological condition selected from the group consisting of presenile and senile dementia, Huntington'"'"'s chorea, tardive dyskinesia, hyperkinesia, mania and Tourette Syndrome, which method comprises administering to a patient suffering from that condition a therapeutically effective amount of one or more compounds of formula I, as defined in claim 1, or a pharmaceutically acceptable acid addition salt thereof.

8. A pharmaceutical composition comprising a compound of formula I, as defined in claim 1, or a pharmaceutically acceptable acid addition salt thereof in admixture with a pharmaceutically acceptable carrier, excipient or diluent.