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US 6,271,231 B1Granted
Pharmaceutically active compounds
AssigneeAstra Aktiebolag
InventorsHåkan Bergstrand, Kostas Karabelas, Peter Sjö
Life of this patent
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Abstract
The present invention provides optionally substituted and/or annulated compounds of formula (I) wherein X, Y, Z and A is each independently carbon or nitrogen, and at least two of X, Y, Z and A are carbon; and pharmaceutically acceptable salts thereof with the proviso that: 3-(1H-Indol-3-yl)-1H-quinoxalin-2-one, 3-(2-Methyl-1H-indol-3-yl)-1H-quinoxalin-2-one, and 3-(1,2-Diphenyl-1H-indol-3-yl)-1H-quinoxalin-2-one are excluded from compounds of formula (I). The invention includes the use of compounds of formula (I) in medical therapy, particularly in the therapy of conditions requiring inhibition of protein kinase C.
Claims11
A compound of formula (IA):
- wherein X, Y, Z, and A is each independently carbon;
- R1, R2, R3, and R4 is each independently H, amino, nitro, halo, C1-6 alkyl, phenylC1-6 alkyl, C1-6 alkoxy, haloC1-6 alkyl, C1-6 alkoxycarbonyl, or absent when the atom to which it would be attached is nitrogen;
- R5 and R6 is each independently H, C1-6 alkyl, hydroxyC1-6 alkyl, aminoC1-6 alkyl, phenylC1-6 alkyl, carboxyC1-6 alkyl, C2-6 alkenyl, (phenylC1-3 alkoxy)C1-3 alkyl, (C1-6 acyloxy)C1-6 alkyl, (C1-6 alkoxycarbonyl)C1-6 alkyl, (mono- or di-C1-6 alkyl)aminoC1-6 alkyl, (C1-6 alkyl)aminocarbonylC1-6 alkyl, (C1-6 acylamino)C1-6 alkyl, (aminoC1-3 alkylphenyl)C1-3 alkyl, or aminodeoxyhexopyranosyl;
- R7 and R8 is each independently H, amino, nitro, hydroxy, halogen, C1-6 alkoxy, phenylC1-6 alkoxy or C1-6 alkoxycarbonyl;
- R9 is H, C1-6 alkyl, phenyl, halophenyl or phenylC1-6 alkyl;
- or a pharmaceutically acceptable salt thereof,
- with the proviso that:
- 3-(1H-indol-3-yl)-1H-quinoxalin-2-one,
- 3-(2-methyl-1H-indol-3-yl)-1H-quinoxalin-2-one, and
- 3-(1,2-diphenyl-1H-indol-3-yl)-1H-quinoxalin-2-one
- are excluded.
8 more elements
A compound selected from the group consisting of:
- 3-[3-(4-Methyl-3-oxo-3,4-dihydro-quinoxalin-2-yl)-indol-1-yl]-propyl-ammonium acetate,
- 3-[3-(6,7-Dichloro-3-oxo-3,4-dihydro-quinoxalin-2-yl)-indol-1-yl]-propyl-ammonium acetate,
- 3-[3-(6,7-Dichloro-3-oxo-3,4-dihydro-quinoxalin-2-yl)-5-methoxycarbonyl-indol-1-yl]-propyl-ammonium acetate,
- 3-[3-(6,7-Dichloro-4-methyl-3-oxo-3,4-dihydro-quinoxalin-2-yl)-5-methoxycarbonyl-indol-1-yl]-propyl-ammonium acetate,
- 3-[5-Methoxycarbonyl-3-(7-methoxy-3-oxo-3,4-dihydro-quinoxalin-2-yl)-indol-1-yl]-propyl-ammonium acetate,
- 3-[3-(4-tert-Butoxycarbonylmethyl-7-methoxy-3-oxo-3,4-dihydro-quinoxalin-2-yl)-5-methoxycarbonyl-indol-1-yl]-propyl-ammonium acetate,
- 3-[3-(4-(3-Ammoniumpropyl)-3-oxo-3,4-dihydro-quinoxalin-2-yl)-indol-1-yl]-propyl-ammonium bis trifluoroacetate,
- Dimethyl-{3-[3-(1-methyl-1H-indol-3-yl)-2-oxo-2H-quinoxalin-1-yl]-propyl}-ammonium trifluoroacetate,
- 3-[6-Benzyloxy-3-(7-methoxy-4-methyl-3-oxo-3,4-dihydro-quinoxalin-2-yl)-indol-1-yl]-propyl-ammonium acetate,
- 3-[5-Benzyloxy-3-(4-tert-butoxycarbonylmethyl-7-methoxy-3-oxo-3,4-dihydro-quinoxalin-2-yl)-indol-1-yl]-propyl-ammonium acetate,
- 3-[2-(4-Chloro-phenyl)-3-(7-methoxy-3-oxo-3,4-dihydro-quinoxalin-2-yl)-indol-1-yl]-propyl-ammonium acetate,
- 3-[2-(4-Chloro-phenyl)-3-(7-methoxy-4-methyl-3-oxo-3,4-dihydro-quinoxalin-2-yl)-indol-1-yl]-propyl-ammonium acetate,
- 3-[3-(6,7-Dichloro-4-methyl-3-oxo-3,4-dihydro-quinoxalin-2-yl)-2-ethyl-indol-1-yl]-propyl-ammonium acetate,
- 3-[3-(5-Methyl-3-oxo-3,4-dihydro-quinoxalin-2-yl)-6-nitro-indol-1-yl]-propyl-ammonium acetate,
- 3-[6-Nitro-3-(6-nitro-3-oxo-3,4-dihydro-quinoxalin-2-yl)-indol-1-yl]-propyl-ammonium acetate,
- 4-[3-(3-Oxo-3,4-dihydro-quinoxalin-2-yl)-indol-1-ylmethyl]-benzyl-ammonium acetate,
- 3-[3-(4-Methyl-3-oxo-3,4-dihydro-quinoxalin-2-yl)-indol-1-ylmethyl]-benzyl-ammonium trifluoroacetate, and
- 3-[3-(4-Benzyl-3-oxo-3,4-dihydro-quinoxalin-2-yl)-indol-1-yl]-propyl-ammonium trifluoroacetate;
- or a free amine.
16 more elements
A compound of formula (II):
- wherein X, Y, Z, and A is each independently carbon;
- R1, R2, R3, and R4 is each independently H, hydroxy, amino, nitro, halo, C1-6 alkyl, phenylC1-6 alkyl, C1-6 alkoxy, haloC1-6 alkyl, C1-6 alkoxycarbonyl, or absent when the atom to which it would be attached is nitrogen;
- R5 and R6 is each independently H, C1-6 alkyl, hydroxyC1-6 alkyl, aminoC1-6 alkyl, phenylC1-6 alkyl, carboxyC1-6 alkyl, C2-6 alkenyl, (phenylC1-3 alkoxy)C1-3 alkyl, (C1-6 acyloxy)C1-6 alkyl, (C1-6 alkoxycarbonyl)C1-6 alkyl, (mono- or di-C1-6 alkyl)aminoC1-6 alkyl, (C1-6 alkyl)aminocarbonylC1-6 alkyl, (C1-6 acylamino)C1-6 alkyl, (aminoC1-3 alkylphenyl)C1-3 alkyl, or aminodeoxyhexopyranosyl;
- R7 and R8 is each independently H, amino, nitro, hydroxy, halogen, C1-6 alkoxy, phenylC1-6 alkoxy or C1-6 alkoxycarbonyl;
- R9 is H, C1-6 alkyl, phenyl, halophenyl or phenylC1-6 alkyl;
- and at least one of R5 and R6 carries a protected amino, carboxy or hydroxy group, or a compound of formula (III)
- wherein R5, R7, R8, and R9 are as defined above, but when R5 carries an amino, carboxy or hydroxy groups, such group is in a protected form;
- and LG is a leaving group.
5 more elements
Dependencies are inferred from the claim text.