Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1993-03-01
1994-09-27
Tsang, Cecilia
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514241, 514249, 514269, 514274, 514292, 544219, 544238, 544298, 544310, 544315, 544318, 544329, 544353, 544354, 544361, 544229, 546 14, 546 85, 546 86, A61K 3153, A61K 31495, A61K 3150, A61K 3144, C07D40100, C07D47102
Patent
active
053507509
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The invention relates to new .beta.-carboline-3-hydroxyalkylcarboxylic acid ester derivatives, their production and use in pharmaceutical agents.
From numerous publications, such as, for example, from EP-A-54 507, it is known that .beta.-carbolines have an affect on the central nervous system and are used as psychopharmaceutical agents.
The compounds substituted according to the invention have a good affinity for the benzodiazepine receptors. For use as pharmaceutical agents it is possibly advantageous if the substances are eliminated more quickly and thus have a shorter duration of action in comparison with other .beta.-carbolines. Such cases exist, for example, in the use as soporific or in patients with a slow metabolism (older patients). Because of the hydroxyl group already present and important for the conjugation and elimination, a shorter duration of action of the compounds according to the invention exists.
SUMMARY OF THE INVENTION
The compounds according to the invention have general formula I ##STR2## in which R.sup.A means halogen, --CHR.sup.1 -R.sup.2 or OR.sup.5 and n is 1 or 2 and optionally substituted phenyl, benzyl or phenoxy radical and optionally substituted phenyl, benzyl or hetaryl radical -alkyl and substituted once to four times with OR.sup.6 and well as their isomers and acid addition salts.
Substituent R.sup.A can be in the A ring in position 5-8, preferably in 5, 6 or 7 position.
The alkyl groups may be both straight chain and branched chain radicals such as, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec. butyl, tert. butyl, pentyl, isopentyl and hexyl.
By halogen is meant fluorine, chlorine, bromine and iodine respectively.
Cycloalkyl respectively stands for cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl.
If R.sup.5 means a hetaryl radical, then it is 5- or 6-membered and contains 1-3 heteroatoms such as nitrogen, oxygen and/or sulfur. For example, the following 5- and 6-ring heteroaromatic compounds can be mentioned: pyridine, pyrimidine, pyrazine, pyridazine, triazine, furan, thiophene, pyrrole, thiazole, imidazole. The hetaryl radical can have a condensed benzene radical such as quinoline, isoquinoline, quinoxaline.
The phenyl, benzyl and hetaryl radical R.sup.5 can be substituted once to three times in any position. Suitable substituents are halogen, nitro, cyano, C.sub.1-4 -alkyl, C.sub.1-4 -alkoxy, trifluoromethyl, SO.sub.2 -C.sub.1-4 -alkyl, amino and C.sub.1-4 -alkoxycarbonyl, and halogens such as fluorine, chlorine and bromine are preferred.
Nitrogen-containing heterocyles optionally substituted with halogen or C.sub.1-4 -alkyl can be considered as preferred hetaryl radicals R.sup.5.
As the substituents of phenyl, benzyl and phenoxy radical R.sup.2, the substituents of the aromatic compounds mentioned for R.sup.5 are suitable, especially halogen such as chlorine and bromine.
If R.sup.6 means a hydroxy protective group, then all protective groups usually used that are not attacked under the reaction conditions are suitable. Examples of such protective groups are cyclic ethers such as tetrahydropyranyl, tetrahydrofuranyl, benzyl, substituted benzyl such as p-methoxybenzyl, 4-methylbenzyl, trityl, allyl, trialkylsilyl such as trimethylsilyl, t-butyldimethylsilyl, that are obtained by reaction of the hydroxy group, for example, with dihydropyran, 2-chlorotetrahydrofuran, benzylhalide, allylhalide or trimethylsilylhalide. If substituent R.sup.6 contains several hydroxy groups, then cyclic acetals or ketals can be present, such as 1,3-dioxane or 1,3-dioxolane radicals such as 2-phenyl-1,3-dioxane, 2,2-dimethyl-1,3-dioxolane, that are produced for example by reaction with acetone, an enolether, 1,1-alkyl dihalide or acetone dimethyl ketal.
If the chiral centers are present, compounds of formula I can be present in the form of stereoisomers and their mixtures.
The physiologically compatible acid addition salts are derived from the known inorganic and organic acids such as, for example, hydrochloric acid, hydro
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Huth Andreas
Krause Werner
Kruger Martin
Schmiechen Ralph
Schneider Herbert
Schering Aktiengesellschaft
Tsang Cecilia
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