Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-12-21
1998-09-15
Dentz, Bernard
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
546148, 546145, 546146, 546147, A61K 3147, C07D21704
Patent
active
058078681
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/EP94/01926 which is now published as WO 95/00489 on Jan. 5, 1995.
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 or in the treatment of psychoses (for example schizophrenia), Parkinson'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 the form of individual enantiomers, racemates, or other mixtures of enantiomers, in which: 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 substituted by one or two alkyl groups each independently of 1 to 3 carbon atoms; to 3 carbon atoms optionally substituted by hydroxy or alkoxy containing 1 to 3 carbon atoms; substituted by one or more alkyl groups containing 1 to 3 carbon atoms, 3 to 8 carbon atoms optionally substituted by one or more substitutents selected from alkyl of 1 to 3 carbon atoms, hydroxy, alkoxy of 1 to 3 carbon atoms, polyhaloalkyl of 1 to 3 carbon atoms, oxo, alkylthio of 1 to 3 carbon atoms, alkylsulphinyl of 1 to 3 carbon atoms or alkylsulphonyl of 1 to 3 carbon atoms, said alicyclic group being optionally fused to one or more further rings (for example a benz ring) to form a polycyclic group or (b) a saturated or unsaturated aliphatic chain containing 1 to 12 carbon atoms optionally substituted by one or more substituents selected from alkyl of 1 to 3 carbon atoms, hydroxy, alkoxy of 1 to 3 carbon atoms, polyhaloalkyl of 1 to 3 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, oxo, alkylthio of 1 to 3 carbon atoms, alkylsulphinyl of 1 to 3 carbon atoms or alkylsulphonyl of 1 to 3 carbon atoms, or (c) a 5 or 6 membered heterocyclic ring containing one or more N or O atoms or SO.sub.n groups in which n is 0, 1 or 2, said ring being optionally substituted by one or more substituents selected from alkyl of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms, hydroxy or halo and said ring being optionally fused to one or more further rings to form a polycyclic group;
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 the form of individual enantiomers, racemates, or other mixtures of enantiomers, 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 the form of individual enantiomers, racemates, or other mixtures of enantiomers, 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 me
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Crew Andrew Philip Austin
Johnston David Norman
Sargent Bruce Jeremy
Aulakh Charanjit S.
Dentz Bernard
Knoll Aktiengesellschaft
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