Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1995-05-03
1997-08-19
McKane, Joseph
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
544364, 544365, A61K 31495, C07D40104, C07D40114
Patent
active
056589107
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/SE 93/00565 filed Jun. 23, 1993.
FIELD OF THE INVENTION
The present invention relates to novel bisphenylpiperazine-nicotinic acid esters and acceptable acid salts thereof, to process for the preparation of such compounds as well as new intermediates useful in the preparations of said compounds. Further, the invention relates to pharmaceutical preparations containing the said compounds and the use of said compounds for treatment of mental disorder.
An object of this invention is to provide compounds for therapeutic use, especially compounds having a therapeutic effect via the central nervous system (CNS). An additional object is to provide compounds having an effect on the 5-hydroxytryptamine (5-HT) receptors in meals including man.
PRIOR ART
Various pyridyl- and pyrimidyl derivatives 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, of which the anxiolytic effect is thought to be mediated via the 5-hydroxytryptamine receptors. ##STR2##
In the U.S. Pat. No. 4,937,245, compounds of the general formula I is disclosed ##STR3## wherein A is selected from pyridyl or pyrimidyl group, e.g. ##STR4## wherein preferably R.sub.6 is hydrogen and R.sub.7 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
The esters of 3-pyridinecarboxylic acid(2-(4-(4,4-bis(4-fluorophenyl)butyl)-1-piperazinyl) of the present invention have unexpectedly been found to show pharmacological properties superior to compounds known in the art.
Thus the present invention provides novel compounds of the general formula (II). ##STR5##
R is selected from saturated or unsaturated alkyls, saturated or unsaturated cycloalkyls, heterocyclic compounds or from; ##STR6## wherein G is carbon or nitrogen; m is 0-10; from hydrogen, halogen, alkyl having 1 to 5 carbon atoms , electron donor groups such as alkoxy having 1-5 carbon atoms or hydroxy, electron acceptor groups selected from cyano, nitro, trifluoroalkyl or amide, (--CONH.sub.2) and the pharmacologically active salts thereof; include straight or branched hydrocarbon groups;
The compounds of formula (II) have basic properties and, consequently, they may be converted to their therapeutically active acid addition salts by treatment with appropriate acids; inorganic acids such as hydrochloric, hydrobromic, sulphuric, nitric and phosphoric acid, or organic acids such as acetic, propanoic, glycolic, lactic, malonic, 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 (II) and their pharmaceutically acceptable salts have valuable pharmacological properties, making them useful for the treatment of mental disorders such as, psychoses, depression, 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-hydroxytrypcamine (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., buspirone and ipsapirone, 5-HT.sub.2 antagonists e.g. amperozide and ritanserin, 5-HT uptake inhibitors e.g. fluoxetine and paroxetine.
Since 5-HT.sub.1A and 5-HT.sub.2 receptors have been found to interact functionally, compounds with a combined 5-HT.sub.1A agonistic and 5-HT.sub.2 antagonistic activity would represent very interesting drugs for the treatment of patients suffering from mental disorders.
The compounds of the present invention show a high affinity for 5-HT.sub.1A and 5-HT.sub.2 receptors and they have also b
REFERENCES:
patent: 4937245 (1990-06-01), Fex et al.
Drug Evaluations Annual, American Medical Association, 242-243 1993.
Singh et al., Alcohol Drinking in Rats is Attenuated by the Mixed 5-HT1 Agonist / 5-HT2 Antagonist, Alcohol, 10(3), pp. 243-248, published Apr. 28, 1993. Note: Article is currently unavailable to the examiner, so only the abstract is provided Apr. 28, 1993.
Abramo Lisbeth
Andersson Gunnar
Bjork Anders
Ludwig Catarina
Lundstedt Torbjorn
McKane Joseph
Myers, Jr. Richard S.
Pharmacia AB
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