Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...
Patent
1991-08-07
1994-12-27
Raymond, Richard L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Nitrogen containing other than solely as a nitrogen in an...
564428, A61K 31135, C07C21774
Patent
active
053766873
DESCRIPTION:
BRIEF SUMMARY
DESCRIPTION
1. Field of the Invention
The present invention relates to the (S)enanantiomers of new substituted-3-amino-chromans, thiochromans, and tetralins and salts thereof, processes for their preparation, pharmaceutical compositions containing said therapeutically active compounds as well as new intermediates useful in the preparation of the therapeutically active compounds and to the use of said active compounds in therapy.
An object of the invention is to provide compounds for therapeutic use, especially compounds having a therapeutic activity via the central nervous system (CNS). A further object is to provide compounds having a selective effect on 5-hydroxy-tryptamine receptors in meals including man.
2. Prior Art
Therapeutically useful 3-amino-dihydro-[1]-benzopyrans and benzothiopyrans having effect on 5-hydroxy-tryptamine neurons in meals are disclosed in EP 0222 996.
These compounds are defined by the formula ##STR2## wherein Z is 0 or S; R.sub.2 together form a ring with 4-6 carbon atoms; aryloxy or when Z is S and R.sub.3 is hydroxy, lower alkoxy, aryl lower alkoxl, acyloxy or aryloxy when Z is O and R.sub.3 is in 5- or 8-position when Z is O; mono- or di-S-oxides thereof when Z is S, and pharmaceutically acceptable salts thereof.
DISCLOSURE OF THE INVENTION
The object of the present invention is to obtain new compounds which have a high affinity to the 5-hydroxy-tryptamine receptors in the central nervous system at the same time as they act as agonists, partial agonists or antagonists on the serotonin receptors.
Thus, a group of new compounds of the formula I of the present invention, salts and prodrugs thereof are useful in therapeutic treatment of 5-hydroxy-tryptamine mediated states and disorders such as depression, anxiety, anorexia, senile dementia, Alzheimer's disease, migraine, termoregulator and sexual disturbances. Further aspects of the invention are related to the use of the compounds, enantiomers and salts thereof in pain control and in modulation of the cardiovascular system.
Thus, the invention provides compounds of the formula ##STR3## wherein X is O, CH.sub.2, S, SO or SO.sub.2 ayclic alkyl groups having 1 to 6 carbon atoms, for example methyl, ethyl, n-propyl, i-propyl, n-buryl, i-butyl, t-butyl, n-pentyl, i-pentyl, t-pentyl, n-hexyl, i-hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methylcyclopropyl, ethylcyclopropyl, methylcyclobutyl. Preferred alkyl groups have 1 to 4 carbon atoms.
C.sub.2 -C.sub.6 alkenyl in formula I representing straight or branched carbon atom chains having 2 to 6 carbon atoms and containing one or two double bonds, for example allyl, proponyl, isopropenyl, butenyl, isobutenyl, pentenyl, isopentenyl. Preferred alkenyl groups have 2 to 4 carbon atoms and one double bond.
R.sub.1 and R.sub.2 may together form a 5- or 6-membered ring containing 1 or 2 heteroatoms selected from N, O and S.
A further aspect of the invention is a pharmaceutical preparation containing as active ingredient a compound according to formula II. ##STR4## wherein X is O, CH S, SO or SO.sub.2
C.sub.1 -C.sub.6 alkyl in formula II representing straight, branched and cyclic alkyl groups having 1 to 6 carbon atoms, for example methyl, ethyl, n-propyl, i-propyl, n-buryl, i-buryl, t-butyl, n-pentyl, i-pentyl, t-pentyl, n-hexyl, i-hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methylcyclopropyl, ethylcyclopropyl, methylcyclobutyl. Preferred alkyl groups have 1 to 4 carbon atoms.
C.sub.2 -C.sub.6 alkenyl in formula II representing straight or branched carbon atom chains having 2 to 6 carbon atoms and containing one or two double bonds, for example allyl, propenyl, isopropenyl, butenyl, isobutenyl, pentenyl, isopentenyl. Preferred alkenyl groups have 2 to 4 carbon atoms and one double bond.
R.sub.1 and R.sub.2 may together form a 5- or 6-membered ring containing 1 or 2 heteroatoms selected from N, O and S.
Especially preferred are compounds according to the invention where R is fluorine and R.sub.1, R.sub.2, R.sub.3 are selected among methyl, ethyl and n-propyl.
The
REFERENCES:
patent: 5225596 (1993-07-01), Carlsson et al.
DeMarinss et al, Chemical Abstracts, vol. 96 (1982) 51940w.
Heible et al, chemical Abstracts, vol. 97 (1982) 16659k.
Holz et al, Chemical Abstracts, vol. 98 (1983) 11098n.
Singh et al, Chemical Abstracts, vol. 100 (1984) 79479c.
Weinstock et al, J. Med. Chem., vol. 29 (1986) pp. 1615-1627.
Arvidsson, et al. 1981 "8-Hydroxy-2-(di-n-propylamino) tetralin, a New Centrally Acting 5-Hydroxytryptamine Receptor Agonist" J. Med. Chem. 24:921-923.
Middlemiss, et al. 1983 "8-Hydroxy-2(di-n-propylamino)-tetralin Discriminates between Subtypes of the 5-HT.sub.1 Recognition Site" Eur. J. Pharm. 90: 151-153.
Hacksell Uli A.
Hillver Sven-Erik
Aktiebolaget Astra
Raymond Richard L.
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