Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1995-01-31
1997-07-29
Grumbling, Matthew V.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
544295, 544360, 544364, 544365, A61K 31495, A61K 31505, C07D40306
Patent
active
056522401
DESCRIPTION:
BRIEF SUMMARY
This is a national stage application filed under 35 USC 371 of PCT/SE93/00632, filed Jul. 16, 1993, published as WO94/03430, Feb. 17, 1994.
BACKGROUND
There is an urgent need for efficient drugs in the treatment of mental disorders which are more effective and which have fewer side effects than the drugs in clinical use today. Antipsychotic drugs in current use produce a range of troublesome extrapyramidal movement disorders (e.g. acute dystonic reactions and tardive dyskinesia) and are poor in ameliorating the negative symptoms (e.g. restricted or blunted emotional arousal) of schizophrenia. The main disadvantage of the anti-depressants is that they fail to alleviate depression in 30 to 40% of patients. Anxioltyics are commonly associated with addictive properties.
PRIOR ART
Various pyridyl- and pyrimidyl-piperazine derivates pharmacologically active in the central nervous system are known in the art. Some representative examples can be mentioned. Azaperone, a neuroleptic drug of the butyrophenone series, is a sedative for pigs. Buspirone is an anxiolytic. The anxiolytic effect is thought to be mediated via effects on the 5HT-receptors. ##STR2##
In the U.S. Pat. No. 4,937,245, compounds of the general formula C is disclosed ##STR3## wherein A is selected from pyridyl or pyrimidyl group, e.g. ##STR4## wherein preferably R6 is hydrogen and R7 is cyano, amides, methoxy or hydrogen substituent in the 3-position of the pyridyl ring, useful for the treatment of mental disorders, such as psychoses, depression and anxiety.
DESCRIPTION OF THE INVENTION
According to the invention there are provided novel compounds having the general formula (I) ##STR5## wherein Ar are the same or different and selected from ##STR6## wherein R.sub.3 is fluoro or hydrogen R.sub.1 and R.sub.2 are the same or different and selected from hydrogen or alkyl; preferably oxygen. ##STR7## R.sub.4 and R.sub.5 are the same or different and selected from hydrogen, halogen, lower alkyl, electron donor groups such as lower alkoxy or hydroxy, electron acceptor groups such as cyano, nitro, trifluoromethyl, COOR.sub.6, CONR.sub.7 R.sub.8 or CO--B; wherein R.sub.6 is hydrogen or lower alkyl; R.sub.7 and R.sub.8 are the same or different selected from hydrogen, lower alkyl or cycloalkyl; ##STR8## wherein m is 1, 2, 3 or 4.
R.sub.9 is selected from hydrogen or lower alkyl. And the pharmacologically active salts thereof. Used in the foregoing definitions the term lower alkyl is meant to include straight and branched, saturated and unsaturated hydrocarbon groups having from 1 to 5 carbon atoms; the term cycloalkyl is meant to include cyclic, saturated and unsaturated hydrocarbon groups have from 3 to 8 carbon atoms, the term lower alkoxy is meant to include straight or branched, saturated or unsaturated alkoxy groups having from 1 to 5 carbon atoms; the term halogen is meant to include fluoro, and bromo.
The compounds of formula (I) have basic properties and, consequently, they may be converted to their therapeutically active acid addition salts by treatment with appropriated acids; e.g. inorganic acids such as hydrochloric, hydrobromic, sulfuric, nitric and phosphoric acid, or organic acids such as acetic, propanoic, glycolic, lactic, malonic, oxalic, succinic, fumaric, tartaric, citric and pamoic acid.
Conversely, the salt form can be converted into the free base form by treatment with alkali.
The compounds of formula (I) and their pharmaceutically acceptable salts have valuable pharmacological properties, making them useful for the treatment of mental disorders such as psychoses, depression and anxiety senile dementia, Alzheimer's disease, anorexia and substance abuse disorders. Stress and anxiety in animals can also be treated.
Clinical studies have lent support to 5-hydroxytryptamine (5-HT) as being important in the pathogenesis of mental disorders, such as psychoses, depression, anxiety and substance abuse disorders. Considerable current activities are directed in the discovery of new psycho tropic drugs such as 5-HT.sub.1A agonists, e.g.,
REFERENCES:
patent: 4292321 (1981-09-01), Pattison
patent: 4766215 (1988-08-01), Abou-Gharbia et al.
patent: 4908365 (1990-03-01), Buzas et al.
patent: 4937245 (1990-06-01), Fex et al.
patent: 4994459 (1991-02-01), Butera et al.
patent: 4994460 (1991-02-01), Dextraze et al.
patent: 5418236 (1995-05-01), Carmosin et al.
Vadodaria et al, J. Med. Chem., vol. 12, pp. 860-865 (1969).
Burger, Medical Chemistry, Third Edition, Part I, pp. 74-77 (1970).
Abramo Lisbeth
Brodszki Martin
Lundstedt Torbjorn
Nordvi Curt
Olsson Knut Gunnar
Grumbling Matthew V.
Pharmacia Aktiebolag
LandOfFree
Pyridyl-and pyrimidylpiperazine derivatives does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Pyridyl-and pyrimidylpiperazine derivatives, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pyridyl-and pyrimidylpiperazine derivatives will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-633942