Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1998-08-06
2000-10-03
Kight, John
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
544343, 544345, 544342, 51425302, 5142521, 514249, 514287, 514 70, 546 64, A61K 31495, A61K 3144, C07D24136, C07D47100
Patent
active
061273686
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/DE96/00632 filed Apr. 3, 1996.
The invention relates to anellated .beta.-carbolines, their production and use in pharmaceutical agents.
It is known from numerous publications that .beta.-carbolines have an affinity to the benzodiazepine receptors, although they differ structurally from benzodiazepines, and that they are used as psychopharmaceutical agents because of the affinity to the BDZ receptors. .beta.-Carbolines can have an antagonistic, agonistic or inversely agonistic effect on the properties that are known of BDZ receptors.
It has now been found that the compounds according to the invention have a very good affinity to the benzodiazepine receptors and have a specific inverse agonistic effect on the properties that are known regarding benzodiazepines. The compounds have anxiolytic, anti-amnestic and nootropic activities and improve learning and attentiveness. Because of their action profile, the compounds according to the invention are suitable for the production of pharmaceutical agents for treating geriatric symptoms, as well as to mitigate cognitive deficits and increase vigilance, without serious side effects occurring.
The invention relates to the compounds of formula I, their isomers, tautomers and salts ##STR2## in which
R.sup.3 means hydrogen, C.sub.1-6 alkyl, --CO--R.sup.1, --C.ident.N, phenyl, which optionally is substituted one to three times with C.sub.1-4 alkyl, C.sub.1-4 alkoxy, halogen or --CF.sub.3, ##STR3##
R.sup.4 means hydrogen, C.sub.1-6 alkyl, C.sub.1-4 alkoxy-C.sub.1-2 alkyl,
A represents a 5- to 6-membered unsaturated ring, in which 1-2 C atoms can be replaced by N, O and/or S and can be substituted with R.sup.5 and R.sup.6, and
R.sup.5 and R.sup.6 are the same or different and mean hydrogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, hydroxy, which can be functionally modified, NR.sup.7 R.sup.8, COR, C.sub.1-6 alkyl, which is substituted with optionally functionally modified hydroxy, C.sub.1-4 alkoxy or halogens, a C.sub.6-12 aryl or a 5- to 6-membered hetaryl radical, which contains one to three N, O and/or S atoms, and the aryl and hetaryl radical can be substituted with C.sub.1-4 alkyl, C.sub.1-4 alkoxy, halogen or CF.sub.3, or
R.sup.5 and R.sup.6 together mean a --(CH.sub.2).sub.n group and
R.sup.1 and R mean hydroxy, C.sub.1-6 alkoxy or NR.sup.10 R.sup.11,
R.sup.2 means hydrogen, C.sub.1-4 alkyl or C.sub.1-4 alkoxy-C.sub.1-2 alkyl,
R.sup.9 means hydrogen or C.sub.1-6 alkyl,
n means 3 or 4,
R.sup.7 and R.sup.8 each mean hydrogen, C.sub.1-6 alkyl, acyl or phenyl, which can be substituted with C.sub.1-4 alkyl, C.sub.1-4 alkoxy, halogen or CF.sub.3,
R.sup.10 and R.sup.11 each mean hydrogen, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl or a C.sub.6-12 aryl radical or a 5- to 6-membered hetaryl radical, which contains one to three N, O and/or S atoms, and the aryl and hetaryl radical can be substituted with C.sub.1-4 alkyl, C.sub.1-4 alkoxy, halogen or CF.sub.3.
Alkyl contains respectively 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.
As aryl radicals R.sup.5, R.sup.6, R.sup.10 or R.sup.11, there can be mentioned, for example, phenyl, biphenyl and .alpha.- or .beta.-naphthyl, which optionally are substituted in 1 to 3 places.
If R.sup.5, R.sup.6, R.sup.10 or R.sup.11 means a hetaryl radical, six-membered ring heteroaromatic compounds with up to 3 nitrogen atoms and five-membered ring heteroaromatic compounds with one to two oxygen, sulfur and/or nitrogen atoms are meant, such as, for example, triazine, pyridine, pyrimidine, pyrazine, pyridazine, furan, thiophene, pyrrole, imidazole, thiazole, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, which can be substituted in each case in 1 to 3 places.
Halogen is defined respectively as fluorine, chlorine, bromine and iodine. Cycloalkyl respectively stands for cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl.
Alkyl radical R.sup.5, R.sup.6 can be substituted in 1 to 3 places or else be p
REFERENCES:
Agarwal, et. al., Indian J. Chem., Sect. B, Antiparasitic agents. Part X. Synthesis of 2,7-disubstituted-1,6-dihydropyrido[3,4-b]imidazo[4,5-e]indoles as anthelmintic agents, pp. 843-847, 1990.
Cole Belinda
Hillmann Margrit
Huth Andreas
Olesen Preben
Ottow Eckhard
Kight John
Robinson Binta
Schering Aktiengesellschaft
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