Azabicylo oxime compounds

Abstract

A compound of formula (I) or a pharmaceutically acceptable salt thereof: ##STR1## wherein R 1 represents ##STR2## in which each of p and q independently represents an integer of 2 to 4, r represents an integer of 2 to 4, s represents 1 or 2 and t represents 0 or 1; R 2 is a group OR 4 , where R 4 is C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, a group OCOR 5 where R 5 is hydrogen or R 4 , or a group NHR 6 or NR 7 R 8 where R 6 , R 7 and R 8 are independently C 1-2 alkyl; and R 3 is chloro, fluoro, bromo, cyclopropyl, C 1-3 alkyl substituted by one, two or three halogen atoms, or R 3 is a group (CH 2 ) n R 9 where R 9 is --CN, --OH, --OCH 3 , --SH, --SCH 3 , --C.tbd.CH or --CH═CH 2 and n is O or 1, with the proviso that when n is 0, R 9 is not --OH or --SH.

We claim: 
     
       1. A compound of formula (I) or a pharmaceutically acceptable salt thereof: ##STR72## wherein R 1  represents ##STR73## in which each of p and q independently represents an integer of 2 to 4, r represents an integer of 2 to 4, s represents 1 or 2 and t represents 0 or 1; R 2  is a group OR 4  where R 4  is C 1-4  alkyl, C 2-4  alkenyl, C 2-4  alkynyl, a group OCOR 5  where R 5  is hydrogen or R 4 , or a group NHR 6  or NR 7  R 8  where R 6 , R 7  and R 8  are independently C 1-2  alkyl; and   R 3  is chloro, fluoro, bromo, C 1-3  alkyl substituted by one, two or three halogen atoms, --CN, .[.--CN 2  CN.]., .Iadd.CH 2  CN.Iaddend., --SCH 3 , or --O--CH 3 .   
     
     
       2. A compound according to claim 1, in which p represents 2 and q represents 2 or 3, or the combination (r,s,t) takes the value (2,2,0), (2,1,1), (3,1,1), (2,1,0) or (3,1,0). 
     
     
       3. A compound according to claim 1, in which R 2  is methoxy, ethoxy, allyloxy, propargyloxy, acetoxy or dimethylamino. 
     
     
       4. A compound according to claim 1, in which R 3  is chloro, fluoro, bromo, CN, OCH 3 , or --CH 2  CN. 
     
     
       5. (±) 1-Azabicyclo[2.2.2]oct-3-yl-N-methoxycarboximidoyl chloride, (±) 1-azabicyclo[2.2.2]oct-3-yl-N-methoxycarboximidic acid methyl ester,   (±) α-(methoxyimino)-α-(1-azabicyclo[2.2.2]oct-3-yl)acetonitrile,   (±) 1-azabicyclo[3.2.1]oct-5-yl-N-methoxycarboximidoyl chloride,   (±) α-(methoxyimino)-α-(1-azabicyclo[3.2.1]oct-5-yl)acetonitrile,   (±) 1-azabicyclo[3.2.1]oct-5-yl-N-methoxycarboximidoyl bromide,   (±) exo-1-azabicyclo[2,2,1]hept-3-yl-N-methoxycarboximidoyl chloride,   (±) exo-α-(methoxyimino)-α-(1-azabicyclo[2,2,1]hept-3-yl)acetonitrile,   (±) 1-azabicyclo[2.2.2]oct-3-yl-N-methoxycarboximidoyl fluoride,   1-azabicyclo[2,2,1]hept-5-yl-N-methoxycarboximidoyl chloride,   α-(methoxyimino)-α-(1-azabicyclo[2,2,1]hept-4-yl) acetonitrile,   1-azabicyclo[2,2,1]hept-4-yl-N-methoxycarboximidoyl bromide,   1-azabicyclo[2,2,1]hept-4-yl-N-methoxycarboximidoyl fluoride,   (±) endo-1-azabicyclo[2,2,1]hept-3-yl-N-methoxycarboximidoyl chloride,   (±) endo-α-(methoxyimino)-α-(1-azabicyclo[2,2,1]hept-3-yl)acetonitrile,   (±) exo-1-azabicyclo[2,2,1]hept-3-yl-N-methoxycarboximidoyl bromide,   (±) endo-1-azabicyclo[2,2,1]hept-3-yl-N-methoxycarboximidoyl bromide,   (±) exo-1-azabicyclo[2,2,1]hept-3-yl-N-methoxycarboximidoyl fluoride,   (±) exo-1-azabicyclo[2,2,1]hept-3-yl-N-ethoxycarboximidoyl chloride,   (±) exo-α-(ethoxyimino)-α-(1-azabicyclo[2,2,1]hept-3-yl)acetonitrile,   (±) exo-1-azabicyclo[2,2,1]hept-3-yl-N-ethoxycarboximidoyl bromide, (±) exo-1-azabicyclo[2,2,1]hept-3-yl-N-prop-2-ynyloxy-carboximidoyl chloride,   (±) endo-1-azabicyclo[2,2,1]hept-3-yl-N-prop-2-ynyloxy-carboximidoyl chloride,   (±) exo-3-oxo-3-(1-azabicyclo[2,2,1]hept-3-yl)propionitrile-O-methyl oxime,   (±) endo-3-oxo-3-(1-azabicyclo[2,2,1]hept-3-yl)propionitrile-O-methyl oxime,   (-) α-(methoxyimino)-α-(1-azabicyclo[2.2.2]oct-3-yl) acetonitrile,   (+) α-(methoxyimino)-α-(1-azabicyclo[2.2.2]oct-3-yl) acetonitrile or (±) 1-azabicyclo[3.2.1]oct-5-yl-N-methoxycarboximidoyl fluoride, or a pharmaceutically acceptable salt of any of the foregoing compounds.     
     
     
       6. A compound of formula (IIa): ##STR74## wherein R 2  ' represents hydroxy and R 1  and R 3  are as defined in claim 1 .Iadd.with the proviso that R 3  is not Br.Iaddend.. 
     
     
       7. A pharmaceutical composition which comprises an effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier. 
     
     
       8. A method of treatment or prophylaxis of dementia in mammals, which comprises administering to the sufferer an effective amount of a compound according to claim 1. .Iadd.9. (-) α-(Methoxyimino)-α-(1-azabicyclo[2.2.2]oct-3-yl)acetonitrile or a pharmaceutically acceptable salt thereof. .Iaddend..Iadd.10. (+) α-(Methoxyimino)-α-(1-azabicyclo[2.2.2]oct-3-yl)acetonitrile or a pharmaceutically acceptable salt thereof. .Iaddend..Iadd.11. A pharmaceutical composition comprising an effective amount of a compound defined by claim 9 and a pharmaceutically acceptable carrier therefor. .Iaddend..Iadd.12. A pharmaceutical composition comprising an effective amount of a compound defined by claim 10 and a pharmaceutically acceptable carrier therefor. .Iaddend..Iadd.13. A method of treatment or prophylaxis of dementia in mammals comprising administering to said mammal an effective amount of a compound defined by claim 9. .Iaddend..Iadd.14. A method of treatment or prophylaxis of dementia in mammals comprising administering to said mammal an effective amount of a compound defined by claim 10. .Iaddend.