Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1991-10-23
1993-10-19
Ivy, C. Warren
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
546 14, 546 85, 546 86, C07D47104, A61K 31435
Patent
active
052545636
DESCRIPTION:
BRIEF SUMMARY
The invention relates to new beta-carbolines, their production and use in pharmaceutical agents.
From numerous publications, such as, for example, from EP-A-54507, it is known that beta-carbolines influence the central nervous system and are suitable as psychopharmacological agents. Surprisingly, it was shown that the beta-carbolines, substituted in 3-position according to the invention, are bio-available over a longer period and at the same time exhibit a good affinity for the benzodiazepine receptors.
The compounds according to the invention have general formula I ##STR2## in which R.sup.A means halogen, --CHR.sup.1 -R.sup.2, phenyl or OR.sup.5 and can be single or double and optionally substituted phenyl, benzyl or phenoxy radical, and C.sub.3-7 cycloalkyl or an optionally substituted phenyl, benzyl or hetaryl radical and and monocyclic or bicyclic aryl or hetaryl radical or a C.sub.3-10 cycloalkyl or bicycloalkyl radical as well as their isomers and acid addition salts.
Substituent R.sup.A can be in the A-ring in 5- to 8-position, preferably in 5-, 6- or 7-position.
Alkyl in each case contains both straight-chain and branched-chain radicals, such as, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and tert-butyl.
By halogen is understood, respectively, fluorine, chlorine, bromine and iodine.
Cycloalkyl in each case can stand for cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl and 2-methyl-cyclopropyl, and 3-5 carbon atoms are preferred for substituent R.sup.5.
If R.sup.5 means a hetaryl radical, the latter is 5- or 6-membered and contains 1-2 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, furan, thiophene, pyrrole, thiazole, imidazole.
Heterocycles containing nitrogen and substituted with halogen can optionally be considered as preferred hetaryl radicals R.sup.5.
The substituent of phenyl, benzyl and hetaryl radical R.sup.5 can be single to triple in any position. Suitable substituents are halogens, nitro, cyano, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, amino and C.sub.1-4 alkoxycarbonyl, and in particular fluorine, chlorine and bromine are preferred.
As substituents of phenyl, benzyl and phenoxy radical R.sup.2, the substituents of the aromatic compounds, mentioned for R.sup.5, are suitable, in particular halogens such as chlorine and bromine.
The aryl and hetaryl radical in R.sup.3 can be present as a monocyclic or bicyclic compound and can contain 5-12 ring atoms, preferably 5-9 ring atoms, such as, for example, phenyl, biphenylyl, naphthyl, indenyl as aryl radical, and thienyl, furyl, pyranyl, pyrrolyl, pyrazolyl, pyridyl, pyrimidinyl, pyridazinyl, oxazolyl, isooxazolyl, thiazolyl, isothiazolyl, quinolyl, isoquinolyl, benzo[1]thienyl, benzofuryl as hetaryl radical with 1-2 heteroatoms, such as sulfur, oxygen and/or nitrogen.
The substituent of aryl and hetaryl radical R can be single to double and can be halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, cyano, amino or nitro, and C.sub.1-4 alkyl, C.sub.1-4 alkoxy and amino are preferred.
By a bicycloalkyl radical R is understood, for example, bicycloheptyl and bicyclooctyl.
If a chiral center is present, the compounds of formula I can be present in the form of diastereomers and their mixtures.
The physiologically compatible acid addition salts are derived from the known inorganic and organic acids, such as, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, benzoic acid, maleic acid, fumaric acid, succinic acid, tartaric acid, citric acid, oxalic acid, glyoxylic acid as well as from alkanesulfonic acids and arylsulfonic acids, such as, for example, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, i.a.
As especially preferred embodiments for R, the cycloalkyls, mentioned at the beginning, with 3-5 carbon atoms as well as optionally substituted phenyl, biphenyl, naphthyl a
Andrews John S.
Huth Andreas
Kruger Martin
Rahtz Dieter
Schmiechen Ralph
Davis Zinna N.
Ivy C. Warren
Schering Aktiengesellschaft
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