Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...
Patent
1997-05-29
2000-11-07
Bernhardt, Emily
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Phosphorus containing other than solely as part of an...
514249, 544337, 544354, A61K 31498, A61K 31675, C07F 96509, C07D24144
Patent
active
061437336
DESCRIPTION:
BRIEF SUMMARY
The invention relates to quinoxalinedione derivatives, their production and use in pharmaceutical agents.
It is known that quinoxaline derivatives have an affinity to the quisqualate receptors and, because of the affinity, are suitable as pharmaceutical agents for the treatment of diseases of the central nervous system.
The compounds according to the invention have formula I ##STR2## in which
R.sup.1 means --(CH.sub.2).sub.n --CR.sup.2 H--(CH.sub.2).sub.m --Z and
R.sup.5, R.sup.6, R.sup.7 and R.sup.8 are the same or different and mean hydrogen, C.sub.1-6 alkyl, CF.sub.3, nitro, halogen, cyano, SO.sub.p R.sup.11, SO.sub.2 NR.sup.12 R.sup.13, SO.sub.3 H, SO.sub.3 C.sub.1-6 alkyl, OR.sup.14, optionally substituted aryl or hetaryl, whereby
R.sup.2 means hydrogen or --(CH.sub.2).sub.q --R.sup.3, means hydrogen, hydroxy, C.sub.16 alkoxy or NR.sup.15 R.sup.16,
n, m and q each mean 0, 1, 2 or 3,
Z means POXY, OPOXY, SO.sub.2 R.sup.17, CO.sub.2 R.sup.18, cyano or tetrazole,
R.sup.11 means H, C.sub.1-6 alkyl, phenyl,
p means 0, 1 or 2,
R.sup.12, R.sup.13 and R.sup.18 mean hydrogen or C.sub.1-4 alkyl,
R.sup.14 means H, or C.sub.1-6 alkyl optionally substituted in 1-3 places with halogen,
R.sup.17 means hydroxy, C.sub.1-6 alkoxy or NR.sup.19 R.sup.20,
X and Y are the same or different and mean hydroxy, C.sub.1-6 alkoxy, C.sub.1-4 alkyl or NR.sup.21 R.sup.22,
R.sup.15 and R.sup.16, R.sup.21 and R.sup.22 are the same or different and mean hydrogen, C.sub.1-4 alkyl, aryl, or together with the nitrogen atom form a saturated 5- to 7-membered heterocycle that can contain another oxygen, sulfur or nitrogen atom and can be substituted or form an unsaturated 5-membered heterocycle that can contain 1-3 N atoms and can be substituted,
R.sup.19 and R.sup.20 are the same or different and mean hydrogen, C.sub.1-4 alkyl, or together with the nitrogen atom form a saturated 5- to 7-membered heterocycle that can contain another oxygen, sulfur or nitrogen atom, as well as their isomers or salts, whereby at least one of substituents R.sup.5, R.sup.6, R.sup.7 or R.sup.8 means aryl or hetaryl.
The compounds of general formula I also contain the possible tautomeric forms and comprise the E or Z isomers or, if a chiral center is present, the racemates or enantiomers.
The substituents are preferably in 6- and/or 7-position.
Alkyl is defined respectively as a straight-chain or branched alkyl radical, such as, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, pentyl, isopentyl, hexyl, whereby C.sub.1-4 alkyl radicals are preferred.
Halogen is defined respectively as fluorine, chlorine, bromine and iodine.
Aryl radical R.sup.5, R.sup.6, R.sup.7 or R.sup.8 has 6-12 carbon atoms, such as naphthyl, biphenyl or especially phenyl and can be substituted in one or more places. Hetaryls are defined as optionally substituted 5- or 6-membered heteroatoms with 1-3 nitrogen, oxygen and/or sulfur atoms, which can contain a fused benzene ring, such as, for example, thiophene, furan, oxazole, thiazole or pyridine, pyrimidine, pyrazine, pyridazine, triazine, quinoline, isoquinoline.
As substituents, in each case halogen, C.sub.1-4 alkoxy, nitro, trifluoromethyl, C.sub.1-4 alkyl, NR.sup.23 R.sup.24 or SR.sup.25 can occur in 1 or more places, whereby the meaning of NR.sup.23 R.sup.24 corresponds to radical NR.sup.15 R.sup.16 and the meaning of R.sup.25 corresponds to radical R.sup.14. The heteroaromatic compound can be linked to the quinoxaline in any position, but not on an N atom.
If R.sup.15 and R.sup.16, R.sup.21 and R.sup.22 R.sup.19 and R.sup.20 together with the nitrogen atom form a saturated heterocycle, then, for example, piperidine, pyrrolidine, morpholine, thiomorpholine, hexahydroazepine or piperazine is meant.
If R.sup.15 and R.sup.16, R.sup.21 and R.sup.22 together with the nitrogen atom form an unsaturated heterocycle, then, for example, imidazole, pyrazole, pyrrole and triazole can be mentioned.
If an acid function is contained, the physiologically compatible salts of organic and inorganic bases are suitable as salts, such
REFERENCES:
patent: 5166155 (1992-11-01), Jorgensen et al.
patent: 5714489 (1998-02-01), Lubisch et al.
Shishikura et al, Chemical Abstracts, vol. 125, No. 114689, (1996).
Epperson et al, Bioorganic & Medicinal Chemistry Letters, 3, p. 2801-2804, (1993).
Huth Andreas
Jones Graham H
Kruger Martin
Ottow Eckhard
Schneider Herbert
Bernhardt Emily
Schering Aktiengesellschaft
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