Bicyclo[3.3.1]nonyl-benzamide

Claim 2

A compound of the formula (I) or a pharmaceutically acceptable salt thereof: ##STR28## characterised in that: X is oxygen or sulphur; R 1 is a C 1-6 alkoxy or C 1-6 alkylthio group; R 2 and R 3 are the same or different and are hydrogen, halogen, CF 3 , C 1-7 acyl, C 1-7 acylamino or amino, aminocarbonyl or aminosulphonyl optionally substituted by one or two C 1-6 alkyl groups, C 1-6 alkylsulphonyl, C 1-6 alkylsulphinyl, C 1-6 alkoxy, C 1-6 alkylthio, hydroxy or nitro or R 1 and R 2 taken together are methylenedioxy or ethylenedioxy in which case R 3 is any one of the groups given for R 2 and R 3 above; R 4 is C 1-7 alkyl or a group --(CH 2 ) s R 5 where s is 0 to 2 and R 5 is a C 3-8 cycloalkyl group, or a group --(CH 2 ) t R 6 where t is 1 or 2 and R 6 is a phenyl group optionally substituted by one or two substituents selected from C 1-6 alkyl, C 1-4 alkoxy, trifluoromethyl and halogen, or a thienyl group; and n is 0 to 2; and there are at least two carbon atoms between the benzamide and heterogranatane ring nitrogen atoms.

Claim 3

A compound according to claim 1 or a pharmaceutically acceptable salt thereof characterised in that: R 1 is C 1-6 alkoxy; R 2 and R 3 are the same or different and are hydrogen, halogen, trifluoromethyl, C 1-7 acyl, C 1-7 acylamino, or amino, aminocarbonyl or aminosulphonyl optionally substituted by one or two C 1-6 alkyl groups; C 1-6 alkylsulphonyl, C 1-6 alkylsulphinyl or nitro; or R 1 and R 2 taken together are methylenedioxy or ethylenedioxy, in which case R 3 is any one of the groups given for R 1 and R 2 above; R 4 is C 1-7 alkyl or a group --(CH 2 ) s R 5 where s is 0 to 2 and R 5 is a C 3-8 cycloalkyl group, or a group --(CH 2 ) t R 6 where t is 1 or 2 and R 6 is a phenyl group optionally substituted by one or two substituents selected from C 1-6 alkyl, C 1-6 alkoxy, trifluoromethyl and halogen; X is oxygen or sulphur; n is 0, 1 or 2; and there are at least two carbon atoms between the benzamide and side-chain nitrogen atoms.

Claim 4

A compound according to claim 1 having the formula (IV) or a pharmaceutically acceptable salt thereof: ##STR29## characterised in that:

Claim 5

X and R 4 are as defined in claim 1, and R 9 in hydrogen or C 1-7 alkanoyl.

Claim 6

A compound according to claim 3 having the formula (V) or a pharmaceutically acceptable salt thereof: ##STR30## wherein: R 1 4 is C 5-7 alkyl, and R 9 is as defined in claim 3.

Claim 7

2-Methoxy-5-chloro-4-amino-N-(9-n-hexyl-9-aza-3-oxabicyclo[3.3.1]non-7β-yl)benzamide, 2-Methoxy-5-chloro-4-amino-N-[9-(3'-methylbutyl)-9-aza-3-oxabicyclo[3.3.1]non-7β-yl)benzamide, 2-Methoxy-5-chloro-4-acetamido-N-(9-n-hexyl-9-aza-3-oxabicyclo[3.3.1]non-7.beta.-yl)benzamide, or 2-Methoxy-5-chloro-4-amino-N-[9-(3'-methylbutyl)-9-aza-3-oxabicyclo[3.3.1]non-7β-yl)benzamide, or a pharmaceutically acceptable salt thereof.

Claim 8

2-Methoxy-5-chloro-4-amino-N-(9-n-hexyl-9-aza-3-oxabicyclo[3.3.1]non-7β-yl)benzamide, 2-Methoxy-5-chloro-4-amino-N-[9-(3'-methylbutyl)-9-aza-3-oxabicyclo[3.3.1]non-7β-yl)benzamide, 2-Methoxy-5-chloro-4-acetamido-N-(9-n-hexyl-9-aza-3-oxabicyclo[3.3.1]non-7.beta.-yl)benzamide, or 2-Methoxy-5-chloro-4-amino-N-[9-(3'-methylbutyl)-9-aza-3-oxabicyclo[3.3.1]non-7β-yl)benzamide, or a pharmaceutically acceptable salt thereof.

Claim 9

A compound according to claim 3 having the formula (VI): ##STR31## wherein: R 2 4 is a group --(CH 2 ) t R 1 wherein t is 1 or 2 and R 1 6 is optionally substituted phenyl as defined in formula (I); cyclohexylmethyl; or 2-thienylmethyl, and R 9 is as defined in claim 3.

Claim 10

2-Methoxy-5-chloro-4-amino-N-(9-benzyl-9-aza-3-oxabicyclo[3.3.1]non-7β-yl)benzamide, 2-Methoxy-5-chloro-4-amino-N-[9-(4'-chlorobenzyl)-9-aza-3-oxabicyclo[3.3.1]non-7β-yl]benzamide, 2-Methoxy-5-chloro-4-amino-N-[9-(3',4'-dichlorobenzyl)-9-aza-3-oxabicyclo[3.3.1]non-7β-yl]benzamide, 2-Methoxy-5-chloro-4-amino-N-[9-(3'-trifluoromethylbenzyl)-9-aza-3-oxabicyclo[3.3.1]non-7β-yl]benzamide, 2-Methoxy-5-chloro-4-amino-N-[9-(4'-methylbenzyl)-9-aza-3-oxabicyclo[3.3.1]non-7β-yl]benzamide, 2-Methoxy-5-chloro-4-amino-N-[9-(2'-thenyl)-9-aza-3-oxabicyclo[3.3.1]non-7.beta.-yl]benzamide, 2-Methoxy-5-chloro-4-amino-N-[9-(cyclohexylmethyl)-9-aza-3-oxabicyclo[3.3.1]non-7β-yl]benzamide, 2-Methoxy-5-chloro-4-acetamido-N-(9-benzyl-9-aza-3-oxabicyclo[3.3.1]non-7.beta.-yl)benzamide, 2-Methoxy-5-chloro-4-acetamido-N-[9-(4'-chlorobenzyl)-9-aza-3-oxabicyclo[3.3.1]non-7β-yl]benzamide, 2-Methoxy-5-chloro-4-acetamido-N-[9-(3',4'-dichlorobenzyl)-9-aza-3-oxabicyclo[3.3.1]non-7β-yl]benzamide, 2-Methoxy-5-chloro-4-acetamido-N-[9-(3'-trifluoromethylbenzyl)-9-aza-3-oxabicyclo[3.3.1]non-7β-yl]benzamide, 2-Methoxy-5-chloro-4-acetamido-N-[9-(4'-methylbenzyl)-9-aza-3-oxabicyclo[3.3.1]non-7β-yl]benzamide, 2-Methoxy-5-chloro-4-acetamido-N-[9-(2'-thenyl)-9-aza-3-oxabicyclo[3.3.1]non-7β-yl]benzamide, or 2-Methoxy-5-chloro-4-acetamido-[9-(cyclohexylmethyl)-9-aza-3-oxabicyclo[3.3.1]non-7β-yl]benzamide, or a pharmaceutically acceptable salt thereof.

Claim 11

2-Methoxy-5-chloro-4-amino-N-(9-benzyl-9-aza-3-oxabicyclo[3.3.1]non-7β-yl)benzamide, 2-Methoxy-5-chloro-4-amino-N-[9-(4'-chlorobenzyl)-9-aza-3-oxabicyclo[3.3.1]non-7β-yl]benzamide, 2-Methoxy-5-chloro-4-amino-N-[9-(3',4'-dichlorobenzyl)-9-aza-3-oxabicyclo[3.3.1]non-7β-yl]benzamide, 2-Methoxy-5-chloro-4-amino-N-[9-(3'-trifluoromethylbenzyl)-9-aza-3-oxabicyclo[3.3.1]non-7β-yl]benzamide, 2-Methoxy-5-chloro-4-amino-N-[9-(4'-methylbenzyl)-9-aza-3-oxabicyclo[3.3.1]non-7β-yl]benzamide, 2-Methoxy-5-chloro-4-amino-N-[9-(2'-thenyl)-9-aza-3-oxabicyclo[3.3.1]non-7.beta.-yl]benzamide, 2-Methoxy-5-chloro-4-amino-N-[9-(cyclohexylmethyl)-9-aza-3-oxabicyclo[3.3.1]non-7β-yl]benzamide, 2-Methoxy-5-chloro-4-acetamido-N-(9-benzyl-9-aza-3-oxabicyclo[3.3.1]non-7.beta.-yl)benzamide, 2-Methoxy-5-chloro-4-acetamido-N-[9-(4'-chlorobenzyl)-9-aza-3-oxabicyclo[3.3.1]non-7β-yl]benzamide, 2-Methoxy-5-chloro-4-acetamido-N-[9-(3',4'-dichlorobenzyl)-9-aza-3-oxabicyclo[3.3.1]non-7β-yl]benzamide, 2-Methoxy-5-chloro-4-acetamido-N-[9-(3'-trifluoromethylbenzyl)-9-aza-3-oxabicyclo[3.3.1]non-7β-yl]benzamide, 2-Methoxy-5-chloro-4-acetamido-N-[9-(4'-methylbenzyl)-9-aza-3-oxabicyclo[3.3.1]non-7β-yl]benzamide, 2-Methoxy-5-chloro-4-acetamido-N-[9-(2'-thenyl)-9-aza-3-oxabicyclo[3.3.1]non-7β-yl]benzamide, or 2-Methoxy-5-chloro-4-acetamido-[9-(cyclohexylmethyl)-9-aza-3-oxabicyclo[3.3.1]non-7β-yl]benzamide, or a pharmaceutically acceptable salt thereof.

Claim 12

A compound according to claim 1 having the formula (IX) or a pharmaceutically acceptable salt thereof: ##STR32## wherein: R 1 1 is C 1-6 alkoxy; R 1 2 and R 1 3 are the same or different and are hydrogen, aminosulphonyl optionally substituted by one or two C 1-6 alkyl groups, C 1-6 alkylsulphonyl, C 1-6 alkylsulphinyl, C 1-6 alkoxy or hydroxy or R 1 1 and R 1 2 taken together are methylenedioxy or ethylenedioxy, in which case R 1 3 is any one of the groups given above for R 1 1 and R 1 2 ; and X is oxygen or sulphur and R 2 4 is a group --(CH 2 ) t R 1 wherein t is 1 or 2 and R 1 6 is optionally substituted phenyl as defined with respect to formula (I), cyclohexylmethyl or 2-thienylmethyl.

Claim 13

2-Methoxy-5-methylsulphonyl-N-[9-benzyl-9-aza-3-thiabicyclo[3.3.1]non-7β-yl]benzamide, or a pharmaceutically acceptable salt thereof.

Claim 14

2-Methoxy-5-methylsulphonyl-N-[9-benzyl-9-aza-3-thiabicyclo[3.3.1]non-7β-yl]benzamide, or a pharmaceutically acceptable salt thereof.

Claim 15

A compound according to claim 8 having the formula (XI) or a pharmaceutically acceptable salt thereof: ##STR33## wherein: X, R 1 1 and R 2 4 are as defined in claim 8. R 2 2 and R 3 3 are the same or different and are C 1-6 alkoxy or hydrogen; or R 1 1 and R 2 2 taken together are methylenedioxy or ethylenedioxy, in which case R 3 3 is any one of the groups given above for R 2 2 and R 3 3 .

Claim 16

2,3-Dimethoxy-N-(9-benzyl-9-aza-3-oxabicyclo[3.2.1]non-7β-yl)benzamide, or 2,4,5-Trimethoxy-N-(9-butyl-9-aza-3-oxabicyclo[3.2.1]non-7β-yl)benzamide, or a pharmaceutically acceptable salt thereof.

Claim 17

2,3-Dimethoxy-N-(9-benzyl-9-aza-3-oxabicyclo[3.2.1]non-7β-yl)benzamide, or 2,4,5-Trimethoxy-N-(9-butyl-9-aza-3-oxabicyclo[3.2.1]non-7β-yl)benzamide, or a pharmaceutically acceptable salt thereof.

Claim 18

A pharmaceutical composition having dopamine antagonist activity comprising an effective amount of a compound according to claim 1 or a hydrate or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier.

Claim 19

A method of treatment of maladies in humans comprising the administration of a composition of claim 12 containing an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or a hydrate thereof.