Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1997-02-19
1999-01-19
Berch, Mark L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
5142255, 5142262, 540599, 544 38, 544 39, 544 41, A61K 3154, C07D27930, C07D27928, C07D27926
Patent
active
058613943
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to the use of N-substituted phenothiazines for the production of medicaments, to novel active compounds and to a process for their preparation, in particular to use as cerebrally active agents.
It is already kmown that 10-carboxamido-substituted phenothiazines have an No. 4,833,138 additionally describes phenothiazine derivatives for the treatment of neurotoxic disorders. Effects of some phenothiazines in the intrapleural fluid test are furthermore mentioned in the publication Arch Int. Pharmacodyn. Ther. 173 (1), 44-55, (1968).
It has now been found that N-substituted phenothiazines of the general formula (I) ##STR1## in which R.sup.1 represents a radical of the formula --(CH.sub.2).sub.a --CO--R.sup.6, --(CH.sub.2).sub.a --CO--NR.sup.7 R.sup.8 or --(CH.sub.2).sub.b --R.sup.9, each case having up to 6 carbon atoms, it being possible for the latter to be substituted by halogen or hydroxyl, carbon atoms, which is optionally substituted by halogen, phenyl, amino or straight-chain or branched alkyl having up to 6 carbon atoms, which is optionally substituted by hydroxyl or pyridyl, morpholine, azacycloheptyl or pyrrolidinyl ring, up to 6 carbon atoms,
R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are identical or different and represent hydrogen, halogen or trifluoromethyl, and are thus suitable for use in the control of disorders of the CNS and sickle cell anemia.
In the context of the invention physiologically acceptable salts are preferred.
Physiologically acceptable salts are in general salts of the compounds according to the invention with inorganic or organic acids. Preferred salts are those with inorganic acids such as, for example, hydrochloric acid, hydrobromic acid, phosphoric acid or sulphuric acid, or salts with organic carboxylic or sulphonic acids such as, for example, acetic acid, maleic acid, fumaric acid, malic acid, citric acid, tartaric acid, lactic acid, benzoic acid or methanesulphonic acid, etanesulphonic acid, phenylsulphonic acid, toluenesulphonic acid or naphthalenedisulphonic acid.
The compounds according to the invention can exist in stereoisomeric forms which either behave as image and mirror image (enantiomers), or which do not behave as image and mirror image (diastereomers). The invention relates both to the antipodes and to the racemic forms as well as the diastereomer mixtures. Like the diastereomers, the racemic forms can also be separated into the stereoisomerically uniform constituents in a known manner.
Preferred are those compounds of the general formula (I) in which
R.sup.1 represents a radical of the formula --(CH.sub.2).sub.a --CO--R.sup.6, --(CH.sub.2).sub.a --CO--NR.sup.7 R.sup.8 or --(CH.sub.2).sub.b --R.sup.9, each case having up to 4 carbon atoms, it being possible for the latter to be substituted by fluorine, chlorine or hydroxyl, carbon atoms, which is optionally substituted by chlorine, cyclohexyl or straight-chain or branched alkyl having up to 4 carbon atoms, which is optionally substituted by hydroxyl or pyridyl, morpholine, azacycloheptyl or pyrrolidinyl ring, up to 4 carbon atoms,
R.sup.2 and R.sup.5 are identical or different and represent hydrogen, fluorine, chlorine, bromine or trifluoromethyl,
R.sup.3 and R.sup.4 represent hydrogen,
Particularly preferred are those compounds of the general formula (I)
R.sup.1 represents a radical of the formula --(CH.sub.2).sub.a --CO--R.sup.6, --(CH.sub.2).sub.a --CO--NR.sup.7 R.sup.8 or --(CH.sub.2).sub.b --R.sup.9, each case having up to 4 carbon atoms, it being possible for the latter to be substituted by fluorine, chlorine or hydroxyl, carbon atoms, which is optionally substituted by chlorine, cyclohexyl or straight-chain or branched alkyl having up to 4 carbon atoms, which is optionally substituted by hydroxyl or pyridyl, morpholine, azacycloheptyl or pyrrolidinyl ring, up to 4 carbon atoms,
R.sup.2 and R.sup.5 are identical or different and represent hydrogen, fluorine, chlorine, bromine or trifluoromethyl,
R.sup.3 and R.sup.4 represent hydrogen,
The compounds of the general formula (I) acc
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de Vry Jean-Marie-Viktor
Glaser Thomas
Heine Hans-Georg
Junge Bodo
Schohe-Loop Rudolf
Bayer Aktiengesellschaft
Berch Mark L.
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