Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1994-08-18
1996-05-21
Ivy, C. Warren
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
546145, 546146, 546147, 546148, 546149, 546150, C07D21704, A61K 3147
Patent
active
055190340
DESCRIPTION:
BRIEF SUMMARY
This application is filed under 35 U.S.C. 371 as national stage entry of PCT/EP92/02900, filed 12 Dec. 1992.
The present invention relates to novel tetrahydroisoquinoline compounds, to pharmaceutical compositions containing the compounds, methods of preparing the compounds and the use of the compounds in analgesia and in the treatment of psychoses (for example schizophrenia), Parkinsons's disease, Lesch-Nyan syndrome, attention deficit disorder or cognitive impairment or in the relief of drug dependence or tardive dyskinesia.
The present invention provides tetrahydroisoquinoline compounds of formula I ##STR2## and pharmaceutically acceptable salts thereof, in which:
R.sub.1 represents one or more substituents selected from H, halo, hydroxy, alkyl of 1 to 3 carbon atoms (optionally substituted by hydroxy), alkoxy of 1 to 3 carbon atoms, alkylthio of 1 to 3 carbon atoms, alkylsulphinyl of 1 to 3 carbon atoms, alkylsulphonyl of 1 to 3 carbon atoms, nitro, cyano, polyhaloalkyl of 1 to 3 carbon atoms, polyhaloalkoxy of 1 to 3 carbon atoms, phenyl (optionally substituted by one or more substituents selected from halo, alkyl of 1 to 3 carbon atoms or alkoxy of 1 to 3 carbon atoms), or R.sub.1 is carbamoyl optionally alkylated by one or two alkyl groups each independently of 1 to 3 carbon atoms;
R.sub.2 represents an aliphatic group containing 1 to 3 carbon atoms optionally substituted by hydroxy or alkoxy containing 1 to 3 carbon atoms;
E represents an alkylene chain containing 2 to 5 carbon atoms optionally substituted by one or more alkyl groups containing 1 to 3 carbon atoms,
and G represents phenyl or phenyl substituted by one or more substituents which may be the same or different, and which are independently alkyl of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms, halo, hydroxy, polyhaloalkyl of 1 to 3 carbon atoms, polyhaloalkoxy of 1 to 3 carbon atoms, cyano, alkylthio of 1 to 3 carbon atoms, alkylsulphinyl of 1 to 3 carbon atoms, alkylsulphonyl of 1 to 3 carbon atoms, phenyl (optionally substituted by one or more substituents selected from halo, alkyl of 1 to 3 carbon atoms or alkoxy of 1 to 3 carbon atoms), carbamoyl optionally alkylated by one or two alkyl groups each independently of 1 to 3 carbon atoms, or G represents a phenyl ring having fused thereto a heterocyclic or aromatic carbocyclic ring;
and O-acylated derivatives thereof.
In preferred compounds of formula I, the hydroxy group is in the 7-position. Accordingly one group of preferred compounds of the invention is represented by formula II ##STR3## and pharmaceutically acceptable salts thereof, in which R.sub.1, R.sub.2, E and G are as defined above and O-acylated derivatives thereof.
A preferred group of O-acylated derivatives of compounds of formula I is represented by compounds of formula III ##STR4## and pharmaceutically acceptable salts thereof, in which R.sub.1, R.sub.2, E and G are as defined above and R.sub.7 represents an acyl group derived from a carboxylic acid having 6 to 20 carbon atoms preferably 7 to 18 carbon atoms. In more preferred compounds of formula III, R.sub.7 represents heptanoyl, decanoyl, dodecanoyl, hexadecanoyl or octadecanoyl. In most preferred compounds of formula III, the group OR.sub.7 is in the 7-position.
In preferred compounds of formula I, II or III, R.sub.1 represents H, halo, hydroxy, alkyl of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms, alkylthio of 1 to 3 carbon atoms, nitro, polyfluoroalkyl of 1 to 3 carbon atoms, polyfluoroalkoxy of 1 to 3 carbon atoms or phenyl optionally substituted by fluoro, chloro, bromo, methyl or methoxy. In more preferred compounds of formula I, II or III, R.sub.1 represents H, fluoro, chloro, bromo, hydroxy, methyl, methoxy, phenyl or nitro. In particularly preferred compounds of formula II, R.sub.1 represents one substituent in the 6-position which is H, fluoro, chloro, bromo, hydroxy, methyl, methoxy or phenyl.
In preferred compounds of formula I, II or III, R.sub.2 represents an alkyl group containing 1 to 3 carbon atoms (for example methyl or ethyl) optionally
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Kozlik Antonin
Needham Patricia L.
Sargent Bruce J.
Davis Zinna N.
Ivy C. Warren
The Boots Company PLC
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