Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1996-03-08
1998-05-12
Grumbling, Matthew V.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514212, 5142282, 5142348, 540599, 544 62, 544116, 544119, 544232, 544238, 544243, 544295, 544337, 544354, A61K 31495, C07D41300, C07D41700, C07D24136
Patent
active
057505250
DESCRIPTION:
BRIEF SUMMARY
This application was filed under 35 U.S.C. .sctn.371 from PCT/DE94/00493, filed Apr. 28, 1994.
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, NR.sup.9 R.sup.10, 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 OR.sup.14 and
R.sup.2 means hydrogen or --(CH.sub.2).sub.q, --R.sup.3,
R.sup.3 means hydrogen, hydroxy, C.sub.1-6 alkoxy or NR.sup.15 R.sup.16,
n, m and q each mean 0, 1, 2 or 3,
Z means POXY, OPOXY, OR.sup.17, NR.sup.18 R.sup.19, NH--COR.sup.20, NH--SO.sub.2 R.sup.21, SO.sub.2 R.sup.22, CO.sub.2 R.sup.23, halogen, 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, R.sup.17 and R.sup.23 mean hydrogen or C.sub.1-4 alkyl,
R.sup.14 means H or C.sub.1-6 alkyl optionally substituted one to three times with halogen,
R.sup.20 and R.sup.21 mean C.sub.1-6 alkyl, phenyl or hetaryl optionally substituted with halogen,
R.sup.22 means hydroxy, C.sub.1-6 alkoxy or NR.sup.24 R.sup.25,
X and Y are the same or different and mean hydroxy, C.sub.1-6 alkoxy, C.sub.1-4 alkyl or NR.sup.18 R.sup.19,
R.sup.9 and R.sup.10 are the same or different and mean hydrogen, CO--C.sub.1-6 alkyl, phenyl or C.sub.1-6 alkyl that can optionally be substituted with C.sub.1-4 alkoxy or an amino group optionally mono- or disubstituted with C.sub.1-4 alkyl, or together with the nitrogen atom form a 5- to 7-membered saturated heterocycle that can contain another N, S or O 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.15 and R.sup.16, R.sup.18 and R.sup.19 are the same or different and mean hydrogen, C.sub.1-4 alkyl, phenyl or together with the nitrogen atom form a 5- to 7-membered saturated 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.24 and R.sup.25 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,
and, if R.sup.2 is hydrogen and Z is POXY or CO.sub.2 R.sup.23,
R.sup.5 -R.sup.8 do not mean hydrogen and
if R.sup.2 means hydrogen, Z means POXY or CO.sub.2 R.sup.23 and R.sup.5, R.sup.6, R.sup.7 or R.sup.8 mean CF.sub.3, NO.sub.2, halogen, NH.sub.2 or methyl, disubstituted compounds of formula I are present
and
if R.sup.1 is methanephosphonic acid and R.sup.6 is cyano or substituted imidazole, R.sup.5, R.sup.7 and R.sup.8 cannot be hydrogen at the same time, and
if R.sup.1 is methanephosphonic acid and R.sup.6 is CF.sub.3, NO.sub.2 and R.sup.7 is imidazole, R.sup.5 and R.sup.8 cannot be hydrogen at the same time and
if R.sup.1 means --CH.sub.2 --COOH and R.sup.5 and R.sup.8 mean hydrogen, R.sup.6 and R.sup.7 do not mean halogen or methyl at the same time.
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 to be understood to mean respectively a straight-chain or branched alkyl radical, such as, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, pentyl, isopentyl, hexyl, and C.sub.1-4 alkyl radicals are preferred.
Halogen is to be understood to mean respectively fluorine, chlorine, bromine a
REFERENCES:
patent: 5026704 (1991-06-01), Honore et al.
patent: 5075304 (1991-12-01), Hansen et al.
patent: 5166155 (1992-11-01), Jorgensen et al.
patent: 5283244 (1994-02-01), Sakamoto et al.
patent: 5514680 (1996-05-01), Weber et al.
Lumma et al., Piperazinylquinoxalines with Central Serotoninmimetic Activity, Journal of Medicinal Chemistry, vol. 24, No. 1, pp. 93-101, 1981 .
Huth Andreas
Turski Lechoslaw
Coleman Brenda
Grumbling Matthew V.
Schering Aktiengesellschaft
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