Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1997-01-14
1999-09-28
Dees, Jose' G.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514256, 514318, 514241, 514326, 514333, 544245, 544367, 546193, 546209, 546277, C07D28512, C07D285125, C07D285135, A61K 31495
Patent
active
059589230
DESCRIPTION:
BRIEF SUMMARY
The invention relates to the use of thiazole and thiadiazole compounds. Said compounds have valuable therapeutic properties and can be used to treat disorders which respond to dopamine D.sub.3 receptor ligands.
Compounds which are of the type under discussion here and have physiological activities have been disclosed. Thus, U.S. Pat. No. 4,074,049 describes aminoalkylthiothiadiazoles which act as fungicides and blood platelet aggregation inhibitors. JP-A-2 153 276 describes similar compounds which are used to treat liver disorders.
GB-A-1 053 085 describes aminoalkylthiadiazoles which show antitussive, analgesic, antipyretic and hypoglycemic effects. U.S. Pat. No. 3,717,651 describes 5-mercapto-substituted thiazoles which have herbicidal properties.
WO 89/11 476 describes substituted 2-aminothiazoles as dopaminergic agents which can be used, inter alia, for treating psychoses and disorders of the CNS.
WO 92/22 540 describes aminoalkyl-substituted 5-mercaptothiazoles of the formula: ##STR2## where R.sup.1 is H, C.sub.1 -C.sub.5 -alkyl, unsubstituted or substituted phenyl or thienyl; n is 2-6; and A is ##STR3## where Ar is a phenyl ring which is unsubstituted or substituted once by C.sub.1 -C.sub.5 -alkyl, C.sub.1 -C.sub.5 -alkoxy, amino, halogen, nitro, hydroxyl, trifluoromethyl or cyano, or a pyridyl, pyrimidinyl or thienyl radical. These compounds can be used to treat disorders of the central nervous system, eg. Parkinsonism, schizophrenia and disorders associated with elevated blood pressure.
WO 92/22 542 describes the corresponding 2-amino-5-mercapto-1,3,4-thiadiazole derivatives which can likewise be used to treat disorders of the central nervous system and disorders associated with elevated blood pressure.
WO 92/22 541 describes corresponding 2-amino-1,3,4-thiadiazole derivatives where the alkylene chain is linked directly, not via a sulfur atom, to the thiadiazole residue. These compounds can also be used for treating disorders of the central nervous system and disorders associated with elevated blood pressure.
WO 93/21 179 describes 1-aryl-4-(.omega.-amido-1-alkyl and .omega.-imido-1-alkyl)piperazine compounds. These compounds are dopamine D.sub.2 receptor antagonists and 5-HT.sub.1A receptor agonists. They can be used as antipsychotic agents, for example for treating schizophrenia.
Neurons receive their information inter alia via G protein-coupled receptors. There are numerous substances which exert their effect via these receptors. One of them is dopamine.
Confirmed findings on the presence of dopamine and its physiological function as neurotransmitter have been published. Cells which respond to dopamine are connected with the etiology of schizophrenia and Parkinson's disease. These and other disorders are treated with drugs which interact with dopamine receptors.
By 1990, two subtypes of dopamine receptors had been clearly defined pharmacologically, namely D.sub.1 and D.sub.2 receptors.
Sokoloff et al., Nature 1990, 347: 146-151, found a third subtype, namely D.sub.3 receptors. They are expressed mainly in the limbic system. The D.sub.3 receptors differ structurally from the D.sub.1 and D.sub.2 receptors in about half the amino-acid residues.
The effect of neuroleptics has generally been ascribed to their affinity for D.sub.2 receptors. Recent receptor-binding studies have confirmed this. According to these, most dopamine antagonists, like neuroleptics, have high affinity for D.sub.2 receptors but only low affinity for D.sub.3 receptors.
The prior art compounds described above are such D.sub.2 receptor agonists or antagonists.
We have now found, surprisingly, that the compounds according to the invention have a high affinity for the dopamine D.sub.3 receptor and only a low affinity for the D.sub.2 receptor. They are thus selective D.sub.3 ligands.
The present invention therefore relates to the use of thiazole and thiadiazole compounds of the formula I: ##STR4## where A is a straight-chain or branched C.sub.1 -C.sub.18 -alkylene group which may comprise at least one group selected from O, S, NR.su
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Bach Alfred
Hellendahl Beate
Lansky Annegret
Rendenbach-Muller Beatrice
Teschendorf Hans-Jurgen
BASF - Aktiengesellschaft
Dees Jos,e G.
Qazi Sabiha N.
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