| Sonstiges: |
- Nachgewiesen in: USPTO Patent Applications
- Sprachen: English
- Document Number: 20080039450
- Publication Date: February 14, 2008
- Appl. No: 11/821565
- Application Filed: June 21, 2007
- Claim: 1. A compound of the formula I: [chemical expression included] or a pharmaceutically acceptable salt or N-oxide thereof, wherein X is N or CH; Y and Z are each, independently, selected from N and CH; A is a bond, —NH— or, —N(C1-6 alkyl)-; R1 is H or NH2; Ar is benzofuranyl, indolyl, hydroxyphenyl, thienyl, benzothiophenyl, pyrrolyl, aminocarbonylphenyl, or azaindolyl, each of which is unsubstituted or substituted with from 1-2 substituents independently selected from hydroxy, halogen, —CN, —NO2, C1-6 alkyl, C1-6 alkoxy, acyl, C1-6 alkylsulphonyl, —C(O)NH2, —NH—C(O)—R7, and arylsulphonyl; R2 and R3, are each, independently, located at a position ortho or meta with respect to A; and are each, independently, H, halogen, hydroxy, C1-6 alkyl, hydroxy-C1-6 alkyl, carboxy-C1-6 alkyl, C1-6 alkoxy, C1-6 alkoxy-C1-6 alkoxy, di-C1-6 alkylamino-C1-6 alkoxy, or di-C1-6 alkylaminocarbonyl-C1-6 alkoxy; R4 is located at a position para or meta with respect to A and is —C(O)NR5R6 or —S(O)2NR5R6; R5 is H, C1-6 alkyl, or aryl-C1-6 alkyl; and R6 is H, C1-6 alkyl, halo-C1-6 alkyl, di-C1-6 alkylamino-C1-6 alkyl, mono-C1-6 alkylamino-C1-6 alkyl, amino-C1-6 alkyl, hydroxy-C1-6 alkylamino-C1-6 alkyl, di(hydroxy-C1-6 alkyl)amino-C1-6 alkyl, hydroxy-C1-6 alkyl, dihydroxy-C3-6 alkyl, cycloalkyl, heterocyclyl, heterocyclyl-C1-6 alkyl, or heteroaryl-C1-6 alkyl, wherein the heterocyclyl or heteroaryl is unsubstituted or substituted with from 1-2 substituents independently selected from C1-6 alkyl, C1-6 alkyl-OC(O)—, and aryl-C1-6 alkyl, said C1-6 alkyl-OC(O)— being attached to a ring N atom; or R5 and R6 together with the nitrogen to which they are attached form a 4 to 7 membered heterocyclyl, wherein the 4 to 7 membered heterocyclyl optionally includes a second heteroatom ring member selected from N, S, and O and wherein the 4 to 7 membered heterocyclyl is optionally substituted with from 1-2 substituents independently selected from C1-6 alkyl, C1-2-alkoxy-C2-4-alkyl, heterocyclyl-C1-4 alkyl, hydroxy-C1-6 alkyl, oxo, di-C1-6 alkylamino, mono-C1-6 alkylamino, amino, di-C1-6 alkylamino-C1-6 alkyl, mono-C1-6 alkylamino-C1-6 alkyl, amino-C1-6 alkyl, C3-7 cycloalkyl, heteroaryl-carbonyl, and C1-6 alkyl-OC(O)NH—; or R5 and R6 together with the nitrogen to which they are attached form a 4 to 7 membered heterocyclyl, wherein the 4 to 7 membered heterocyclyl optionally includes a second heteroatom ring member selected from N, S and O, wherein one of the ring atoms of the 4-7 membered heterocyclyl is substituted with two geminal substituents, wherein the two geminal substituents, together with the ring atom to which they are attached, forms an optionally substituted, 5-6 membered heterocyclic spiro ring; and wherein the 4-7 membered heterocyclyl and the 5-6 membered heterocyclic spiro ring are each, independently, further optionally substituted with from 1-2 substituents independently selected from C1-6 alkyl, C1-2-alkoxy-C2-4-alkyl, heterocyclyl-C1-4 alkyl, hydroxy-C1-6 alkyl, oxo, di-C1-6 alkylamino, mono-C1-6 alkylamino, amino, di-C1-6 alkylamino-C1-6 alkyl, mono-C1-6 alkylamino-C1-6 alkyl, amino-C1-6 alkyl, C3-7 cycloalkyl, heteroaryl-carbonyl, and C1-6 alkyl-OC(O)NH—; and R7 is H or C1-6 alkyl; with the provisos that: when R1 is NH2, then A is a bond; and when A is —NH— or —N—C1-6-alkyl, then R1 is H.
- Claim: 2. A compound according to claim 1, of the formula II [chemical expression included] or a pharmaceutically acceptable salt or N-oxide thereof, wherein: X is N or CH; A is a bond or —NH—; R1 is H or NH2; Ar is benzofuranyl, indolyl, hydroxyphenyl, thienyl, benzothiophenyl, or pyrrolyl, each of which is unsubstituted or substituted with from 1-2 substituents independently selected from hydroxy, halogen, C1-6 alkyl, C1-6 alkoxy, acyl, C1-6 alkylsulphonyl, and arylsulphonyl; R2 and R3 are each, independently, located at a position that is ortho or meta with respect to A; and are each, independently, H, halogen, C1-6 alkyl, hydroxy-C1-6 alkyl, carboxy-C1-6 alkyl, or C1-6 alkoxy; R4 is located at a position that is para or meta with respect to A and is —C(O)NR5R6 or —S(O)2NR5R6; R5 is H, C1-6 alkyl, or aryl-C1-6 alkyl; R6 is H, C1-6 alkyl, halo-C1-6 alkyl, di-C1-6 alkylamino-C1-6 alkyl, mono-C1-6 alkylamino-C1-6 alkyl, amino-C1-6 alkyl, hydroxy-C1-6 alkylamino-C1-6 alkyl, di(hydroxy-C1-6 alkyl)amino-C1-6 alkyl, hydroxy-C1-6 alkyl, dihydroxy-C3-6 alkyl, cycloalkyl, heterocyclyl, heterocyclyl-C1-6 alkyl, or heteroaryl-C1-6 alkyl, wherein the heterocyclyl or heteroaryl is unsubstituted or substituted with from 1-2 substituents independently selected from C1-6 alkyl, C1-6 alkyl-OC(O)—, and aryl-C1-6 alkyl, said C1-6 alkyl-OC(O)— being attached to a ring N atom; or R5 and R6 together with the nitrogen to which they are attached form a 4 to 7 membered heterocyclyl, wherein the 4 to 7 membered heterocyclyl optionally includes a second heteroatom ring member selected from N, S and O, and wherein the 4 to 7 membered heterocyclyl is optionally substituted with from 1-2 substituents independently selected from C1-6 alkyl, hydroxy-C1-6 alkyl, di-C1-6 alkylamino, mono-C1-6 alkylamino, amino, di-C1-6 alkylamino-C1-6 alkyl, mono-C1-6 alkylamino-C1-6 alkyl, amino-C1-6 alkyl, C3-7 cycloalkyl, C1-6 alkyl-OC(O)NH— and heteroaryl-carbonyl; with the provisos that: when R1 is NH2, then A is a bond; and when A is —NH— then R1 is H.
- Claim: 3. A compound according to claim 1 having the formula III [chemical expression included] or a pharmaceutically acceptable salt or N-oxide thereof, wherein: Y, Z, A, Ar, R1, R2, R3, R4, R5 and R6 are as defined in claim 1 with the provisos that: when R1 is NH2, then A is a bond; and when A is —NH— or —N—C1-6-alkyl, then R1 is H.
- Claim: 4. A compound according to claim 1 having the formula IV [chemical expression included] or a pharmaceutically acceptable salt or N-oxides thereof, wherein: Y, Z, A, Ar, R1, R2, R3, R4, R5 and R6 are as defined in claim 1 with the provisos that: when R1 is NH2, then A is a bond; and when A is —NH— or —N—C1-6-alkyl, then R1 is H.
- Claim: 5. A compound according to claim 1 wherein Y is N and Z is CH.
- Claim: 6. A compound according to claim 1 wherein Z is N and Y is CH.
- Claim: 7. A compound according to claim 1 wherein both Y and Z is CH.
- Claim: 8. The compound according to claim 1, wherein R2 and R3 are each, independently, located in a position that is ortho or meta with respect to A; and are each, independently, H, halogen, hydroxy, C1-3 alkyl, C1-3 alkoxy, C1-3 alkoxy-C1-3 alkoxy, di-C1-6 alkylamino-C1-6 alkoxy, or di-C1-6 alkylaminocarbonyl-C1-6 alkoxy; R5 is H, C1-3 alkyl, or aryl-C1-3 alkyl; R6 is H, C1-3 alkyl, halo-C1-3 alkyl, di-C1-4 alkylamino-C1-6 alkyl, mono-C1-4 alkylamino-C1-6 alkyl, amino-C1-6 alkyl, hydroxy-C1-3 alkylamino-C1-5 alkyl, di(hydroxy-C1-3 alkyl)amino-C1-5 alkyl, hydroxy-C1-5 alkyl, dihydroxy propyl, cycloalkyl, heterocyclyl, heterocyclyl-C1-4 alkyl, or heteroaryl-C1-3 alkyl, wherein the heterocyclyl or heteroaryl is unsubstituted or substituted with from 1-2 substituents independently selected from C1-3 alkyl, C1-5 alkyl-OC(O)—, or aryl-C1-3 alkyl, said C1-5 alkyl-OC(O)— being attached to a ring N atom, or R5 and R6 together with the nitrogen to which they are attached form a 4 to 7 membered heterocyclyl, wherein the 4 to 7 membered heterocyclyl optionally includes a second heteroatom ring member selected from N and O; and wherein the 4 to 7 membered heterocyclyl is unsubstituted or substituted with from 1-2 substituents independently selected from C1-3 alkyl, hydroxy-C1-3 alkyl, di-C1-3 alkylamino, mono-C1-3 alkylamino, amino, di-C1-3 alkylamino-C1-4 alkyl, mono-C1-3 alkylamino-C1-4 alkyl, amino-C1-4 alkyl, C5-6 cycloalkyl, C1-6 alkyl-OC(O)NH—, C1-2-alkoxy-C2-4-alkyl, heterocyclylmethyl, or heteroarylcarbonyl, or R5 and R6 together with the nitrogen to which they are attached form a 4 to 7 membered heterocyclyl, wherein the 4 to 7 membered heterocyclyl optionally includes a second heteroatom ring member selected from N, S and O, wherein one of the ring atoms of the 4-7 membered heterocyclyl is substituted with two geminal substituents, wherein the two geminal substituents, together with the ring atom to which they are attached, forms an optionally substituted, 5-6 membered heterocyclic spiro ring; and wherein the 4-7 membered heterocyclyl and the 5-6 membered heterocyclic spiro ring are each, independently, further optionally substituted with from 1-2 substituents independently selected from C1-3 alkyl, C1-2-alkoxy-C2-4-alkyl, heterocyclylmethyl, hydroxy-C1-3 alkyl, oxo, di-C1-3 alkylamino, mono-C1-3 alkylamino, amino, di-C1-3 alkylamino-C1-4 alkyl, mono-C1-3 alkylamino-C1-4 alkyl, amino-C1-4 alkyl, C5-7 cycloalkyl, heteroaryl-carbonyl, and C1-6 alkyl-OC(O)NH—; and with the provisos that: when R1 is NH2, then A is a bond; when A is —NH— or —N—C1-6-alkyl, then R1 is H; and when both R2 and R3 are other than H, then both R2 and R3 cannot be located at a position that is ortho with respect to A.
- Claim: 9. The compound of claim 8 wherein R6 is di-C1-3 alkylamino-C1-4 alkyl, mono-C1-3 alkylamino-C1-4 alkyl, amino-C1-4 alkyl, heterocyclyl, or heterocyclyl-C1-3 alkyl, wherein the heterocyclyl is preferably 4, 5, or 6 membered containing 1 or 2 heteroatoms selected from O and N, wherein the heterocyclyl may be unsubstituted or substituted in one or two positions independently with C1-3 alkyl, C1-5 alkyl-OC(O)—, or aryl-C1-3 alkyl, said C1-5 alkyl-OC(O)— being attached to a ring N atom.
- Claim: 10. The compound according to claim 1 wherein R2 is located at a position that is ortho with respect to A, R3 is located at a position that is meta with respect to A, and R4 is located at a position that is para with respect to A.
- Claim: 11. The compound according to claim 1, wherein Ar is hydroxyphenyl, benzofuranyl, aminocarbonylphenyl, or indolyl.
- Claim: 12. The compound of claim 11, wherein A is —NH—, and Ar is 2-benzofuranyl or 2-indolyl.
- Claim: 13. The compound according to claim 1, wherein Ar is azaindolyl.
- Claim: 14. The compound according to claim 13, wherein Ar is 5- or 6-azaindol-2-yl.
- Claim: 15. The compound of claim 1, selected from the group consisting of: 4-{[6-(1H-indol-2-yl)pyrazin-2-yl]amino}-3-methoxy-N-methyl-N-(1-methylpyrrolidin-3-yl)benzamide; 4-[5-amino-6-(1-benzofuran-2-yl)pyrazin-2-yl]-N-[(2S)-2,3-dihydroxypropyl]benzamide; 5-{2-fluoro-4-[(4-methylpiperazin-1-yl)carbonyl]phenyl}-3-(1H-indol-2-yl)pyrazin-2-amine; N-[2-(diethylamino)ethyl]-4-[5-(1H-indol-2-yl)pyridin-3-yl]benzamide; 3-(1-benzofuran-2-yl)-5-{2-fluoro-4-[(4-methylpiperazin-1-yl)carbonyl]phenyl}pyrazin-2-amine; 2-(5-{4-[(4-methylpiperazin-1-yl)carbonyl]phenyl}pyridin-3-yl)-1H-indole; 5-fluoro-2-{6-[4-(morpholin-4-ylcarbonyl)phenyl]pyrazin-2-yl}-1H-indole; 2-{5-[4-(morpholin-4-ylcarbonyl)phenyl]pyridin-3-yl}-1H-indole; N-ethyl-N-(2-hydroxyethyl)-4-[6-(1H-indol-2-yl)pyrazin-2-yl]benzamide; 4-{[6-(1H-indol-2-yl)pyrazin-2-yl]amino}-3-methoxy-N-methyl-N-(1-methylpyrrolidin-3-yl)benzamide; N-[2-(diethylamino) ethyl]-4-{[6-(5-fluoro-1H-indol-2-yl)pyrazin-2-yl]amino}-3-methoxybenzamide; 3-fluoro-4-[6-(6-fluoro-1H-indol-2-yl)pyrazin-2-yl]-N-methyl-N-(1-methylpyrrolidin-3-yl)benzamide; 4-{[6-(5-fluoro-1H-indol-2-yl)pyrazin-2-yl]amino}-3-methoxy-N-methyl-N-(1-methylpyrrolidin-3-yl)benzamide; 6-methyl-2-{6-[4-(morpholin-4-ylcarbonyl)phenyl]pyrazin-2-yl}-1H-indole; 2-{6-[4-(morpholin-4-ylcarbonyl)phenyl]pyrazin-2-yl}-1H-indole; 4-[5-amino-6-(1-benzofuran-2-yl)pyrazin-2-yl]-N-(2,3-dihydroxypropyl)benzamide; 6-(5-fluoro-1H-indol-2-yl)-N-{2-methoxy-4-[(4-methylpiperazin-1-yl)carbonyl]phenyl}pyrazin-2-amine; 3-(1H-indol-2-yl)-5-[4-(morpholin-4-ylcarbonyl)phenyl]pyrazin-2-amine; N-[3-(dimethylamino)propyl]-4-{[6-(1H-indol-2-yl)pyrazin-2-yl]amino}-3-methoxybenzamide; 2-(6-{2-fluoro-4-[(4-methylpiperazin-1-yl)carbonyl]phenyl}pyrazin-2-yl)-1H-indole; tert-butyl 3-[({4-[6-(1H-indol-2-yl)pyrazin-2-yl]benzoyl}amino)methyl]piperidine-1-carboxylate; 2-{6-[2-fluoro-4-(morpholin-4-ylcarbonyl)phenyl]pyrazin-2-yl}-1H-indole; 3-{[6-(1-benzofuran-2-yl)pyrazin-2-yl]amino}-4-methoxy-N-methyl-N-(1-methylpyrrolidin-3-yl)benzamide; 5-[2-fluoro-4-(morpholin-4-ylcarbonyl)phenyl]-3-(1H-indol-2-yl)pyrazin-2-amine; N-[2-(diethylamino)ethyl]-4-{[6-(1H-indol-2-yl)pyrazin-2-yl]amino}-3-methoxybenzamide; tert-butyl (1-{4-[6-(1H-indol-2-yl)pyrazin-2-yl]benzoyl}pyrrolidin-3-yl)carbamate; 6-(1H-indol-2-yl)-N-[2-methoxy-4-(morpholin-4-ylcarbonyl)phenyl]pyrazin-2-amine; 5-fluoro-2-(6-{4-[(4-methylpiperazin-1-yl)carbonyl]phenyl}pyrazin-2-yl)-1H-indole; 4-[5-amino-6-(1-benzofuran-2-yl)pyrazin-2-yl]-N-[1-(hydroxymethyl)-2-methylpropyl]benzamide; 6-(1H-indol-2-yl)-N-[2-methoxy-4-(morpholin-4-ylcarbonyl)phenyl]pyrazin-2-amine; tert-butyl (1-{4-[5-amino-6-(1-benzofuran-2-yl)pyrazin-2-yl]benzoyl}pyrrolidin-3-yl)carbamate; 3-(1-benzofuran-2-yl)-5-[4-(morpholin-4-ylcarbonyl)phenyl]pyrazin-2-amine; 3-(4-{4-[6-(1H-indol-2-yl)pyrazin-2-yl]benzoyl}piperazin-1-yl)-N,N-dimethylpropan-1-amine; 4-{[6-(1-benzofuran-2-yl)pyrazin-2-yl]amino}-3-methoxy-N-methyl-N-(1-methylpyrrolidin-3-yl)benzamide; N-[(2S)-2,3-dihydroxypropyl]-4-[6-(1H-indol-2-yl)pyrazin-2-yl]benzamide; N-[3-(dimethylamino)propyl]-4-[6-(1H-indol-2-yl)pyrazin-2-yl]-N-methylbenzamide; N-(4-{[3-(dimethylamino)pyrrolidin-1-yl]carbonyl}-2-methoxyphenyl)-6-(1H-indol-2-yl)pyrazin-2-amine; 3-(1-benzofuran-2-yl)-5-{4-[(4-methylpiperazin-1-yl)carbonyl]phenyl}pyrazin-2-amine; 3-fluoro-5-[6-(6-fluoro-1H-indol-2-yl)pyrazin-2-yl]-N-methyl-N-(1-methylpyrrolidin-3-yl)benzamide; 6-(1H-indol-2-yl)-N-{2-methoxy-4-[(4-methylpiperazin-1-yl)carbonyl]phenyl}pyrazin-2-amine; 4-[5-amino-6-(1-benzofuran-2-yl)pyrazin-2-yl]-N-{3-[bis(2-hydroxyethyl)amino]propyl}benzamide; N-(2,3-dihydroxypropyl)-4-[6-(1H-indol-2-yl)pyrazin-2-yl]benzamide; 2-(4-{3-fluoro-5-[6-(6-fluoro-1H-indol-2-yl)pyrazin-2-yl]benzoyl}piperazin-1-yl)-N,N-dimethylethanamine; 4-[5-amino-6-(1-benzofuran-2-yl)pyrazin-2-yl]-N-ethyl-N-(2-hydroxyethyl)benzamide; 3-chloro-N-[2-(diethylamino)ethyl]-4-{[6-(5-fluoro-1H-indol-2-yl)pyrazin-2-yl]amino}benzamide, N-[2-chloro-4-(piperazin-1-ylcarbonyl)phenyl]-6-(5-fluoro-1H-indol-2-yl)pyrazin-2-amine, N-[2-chloro-5-methoxy-4-(piperazin-1-ylcarbonyl)phenyl]-6-(5-fluoro-1H-indol-2-yl)pyrazin-2-amine 4-{[6-(5-chloro-1H-indol-2-yl)pyrazin-2-yl]amino}-3-methoxy-N-methyl-N-(1-methylpyrrolidin-3-yl)benzamide N-[2-chloro-4-({4-[3-(dimethylamino)propyl]piperazin-1-yl}carbonyl)phenyl]-6-(1H-indol-2-yl)pyrazin-2-amine N-[2-chloro-4-(piperazin-1-ylcarbonyl)phenyl]-6-(1H-indol-2-yl)pyrazin-2-amine, N-[4-({4-[3-(dimethylamino)propyl]piperazin-1-yl}carbonyl)-2-methylphenyl]-6-(5-fluoro-1H-indol-2-yl)pyrazin-2-amine, N-[3-chloro-4-(piperazin-1-ylcarbonyl)phenyl]-6-(1H-indol-2-yl)pyrazin-2-amine 4-{[6-(6-fluoro-1H-indol-2-yl)pyrazin-2-yl]amino}-3-methoxy-N-methyl-N-(1-methylpyrrolidin-3-yl)benzamide 3-methoxy-4-{[6-(5-methoxy-1H-indol-2-yl)pyrazin-2-yl]amino}-N-methyl-N-(1-methylpyrrolidin-3-yl)benzamide 4-{[6-(7-fluoro-1H-indol-2-yl)pyrazin-2-yl]amino}-3-methoxy-N-methyl-N-(1-methylpyrrolidin-3-yl)benzamide, 4-{[6-(4-fluoro-1H-indol-2-yl)pyrazin-2-yl]amino}-3-methoxy-N-methyl-N-(1-methylpyrrolidin-3-yl)benzamide, 2-[6-({4-[(4-methylpiperazin-1-yl)carbonyl]phenyl}amino)pyrazin-2-yl]-1H-indol-4-ol, 4-[[6-(5-fluoro-1H-indol-2-yl)pyrazin-2-yl](methyl)amino]-N-methyl-N-(1-methylpyrrolidin-3-yl)benzamide, 3-methoxy-4-{[6-(4-methoxy-1H-indol-2-yl)pyrazin-2-yl]amino}-N-methyl-N-(1-methylpyrrolidin-3-yl)benzamide 4-{[6-(6-chloro-1H-indol-2-yl)pyrazin-2-yl]amino}-3-methoxy-N-methyl-N-(1-methylpyrrolidin-3-yl)benzamide, 4-{[6-(5-cyano-1H-indol-2-yl)pyrazin-2-yl]amino}-3-methoxy-N-methyl-N-(1-methylpyrrolidin-3-yl)benzamide 3-methoxy-N-methyl-4-{[6-(5-methyl-1H-indol-2-yl)pyrazin-2-yl]amino}-N-(1-methylpyrrolidin-3-yl)benzamide 3-methoxy-N-methyl-4-{[6-(6-methyl-1H-indol-2-yl)pyrazin-2-yl]amino}-N-(1-methylpyrrolidin-3-yl)benzamide N-[2-(diethylamino)ethyl]-2-fluoro-4-{[6-(1H-indol-2-yl)pyrazin-2-yl]amino}benzamide N-(4-{[(3R)-3-(dimethylamino)pyrrolidin-1-yl]carbonyl}phenyl)-6-(1H-indol-2-yl)pyrazin-2-amine, N-(4-{[(3S)-3-(dimethylamino)pyrrolidin-1-yl]carbonyl}phenyl)-6-(1H-indol-2-yl)pyrazin-2-amine, N-[4-({4-[3-(dimethylamino)propyl]piperazin-1-yl}carbonyl)-3-methoxyphenyl]-6-(1H-indol-2-yl)pyrazin-2-amine 6-(6-methoxy-1H-indol-2-yl)-N-[2-methoxy-4-(piperazin-1-ylcarbonyl)phenyl]pyrazin-2-amine, 6-(4-fluoro-1H-indol-2-yl)-N-[2-methoxy-4-(piperazin-1-ylcarbonyl)phenyl]pyrazin-2-amine N-(4-{[3-(dimethylamino)pyrrolidin-1-yl]carbonyl}-2-methoxyphenyl)-6-(1H-indol-2-yl)pyrazin-2-amine, tert-butyl [1-(4-{[6-(5-fluoro-1H-indol-2-yl)pyrazin-2-yl]amino}-3-methoxybenzoyl)azetidin-3-yl]carbamate, N-[2-(dimethylamino)ethyl]-4-{[6-(1H-indol-2-yl)pyrazin-2-yl]amino}-3-methoxy-N-methylbenzamide, N-azetidin-3-yl-4-{[6-(5-fluoro-1H-indol-2-yl)pyrazin-2-yl]amino}-3-methoxybenzamide N-{4-[(3-aminoazetidin-1-yl)carbonyl]-2-methoxyphenyl}-6-(5-fluoro-1H-indol-2-yl)pyrazin-2-amine, tert-butyl 3-[(4-{[6-(5-fluoro-1H-indol-2-yl)pyrazin-2-yl]amino}-3-methoxybenzoyl)amino]azetidine-1-carboxylate, N-(1,2-diethylpyrazolidin-4-yl)-4-{[6-(1H-indol-2-yl)pyrazin-2-yl]amino}-3-methoxybenzamide, 6-(5-fluoro-1H-indol-2-yl)-N-(2-methoxy-4-{[(3S)-3-methylpiperazin-1-yl]carbonyl}phenyl)pyrazin-2-amine, 6-(5-fluoro-1H-indol-2-yl)-N-(2-methoxy-4-{[(3R)-3-methylpiperazin-1-yl]carbonyl}phenyl)pyrazin-2-amine, N-(4-{[(3R,5S)-3,5-dimethylpiperazin-1-yl]carbonyl}-2-methoxyphenyl)-6-(1H-indol-2-yl)pyrazin-2-amine, N-{4-[(4-ethylpiperazin-1-yl)carbonyl]-2-methoxyphenyl}-6-(1H-indol-2-yl)pyrazin-2-amine, N-(4-{[(3S)-3-(dimethylamino)pyrrolidin-1-yl]carbonyl}-2-methoxyphenyl)-6-(5-nitro-1H-indol-2-yl)pyrazin-2-amine, 6-(1H-indol-2-yl)-N-{4-[(4-isopropylpiperazin-1-yl)carbonyl]-2-methoxyphenyl}pyrazin-2-amine, N-(4-{[(3R)-3-(dimethylamino)pyrrolidin-1-yl]carbonyl}-2-methoxyphenyl)-6-(6-methoxy-1H-indol-2-yl)pyrazin-2-amine, 6-(1H-indol-2-yl)-N-{2-methoxy-4-[(4-methyl-1,4-diazepan-1-yl)carbonyl]phenyl}pyrazin-2-amine, N-[4-(2,7-diazaspiro[4.5]dec-2-ylcarbonyl)-2-methoxyphenyl]-6-(1H-indol-2-yl)pyrazin-2-amine 6-(1H-indol-2-yl)-N-(2-methoxy-4-{[(2S)-2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl]carbonyl}phenyl)pyrazin-2-amine, N-(2-hydroxyethyl)-4-{[6-(1H-indol-2-yl)pyrazin-2-yl]amino}-3-methoxybenzamide, 6-(1H-indol-2-yl)-N-(2-methoxy-4-{[4-(2-methoxyethyl)piperazin-1-yl]carbonyl}phenyl)pyrazin-2-amine, 2-[4-(4-{[6-(1H-indol-2-yl)pyrazin-2-yl]amino}-3-methoxybenzoyl)piperazin-1-yl]ethanol, 4-{[6-(1H-indol-2-yl)pyrazin-2-yl]amino}-3-methoxy-N-piperidin-3-ylbenzamide, N-(4-{[(3R)-3-aminopyrrolidin-1-yl]carbonyl}-2-methoxyphenyl)-6-(1H-indol-2-yl)pyrazin-2-amine, 4-{[6-(1H-indol-2-yl)pyrazin-2-yl]amino}benzamide, 6-(1H-indol-2-yl)-N-[4-(morpholin-4-ylcarbonyl)phenyl]pyrazin-2-amine N-(4-{[(3S)-3-aminopyrrolidin-1-yl]carbonyl}-2-methoxyphenyl)-6-(1H-indol-2-yl)pyrazin-2-amine 4-{[6-(1H-indol-2-yl)pyrazin-2-yl]amino}-3-methoxy-N-[(3S)-pyrrolidin-3-yl]benzamide 4-{[6-(1H-indol-2-yl)pyrazin-2-yl]amino}-3-methoxy-N-[(3R)-pyrrolidin-3-yl]benzamide, N-(4-{[(3R)-3-aminopyrrolidin-1-yl]carbonyl}-2-methoxyphenyl)-6-(5-fluoro-1H-indol-2-yl)pyrazin-2-amine, 2-{[6-(5-fluoro-1H-indol-2-yl)pyrazin-2-yl]amino}-5-(piperazin-1-ylcarbonyl)phenol, 2-[6-({4-[(4-methylpiperazin-1-yl)carbonyl]phenyl}amino)pyrazin-2-yl]-1H-indole-5-carboxamide, N-{2-[2-(dimethylamino)ethoxy]-4-[(4-methylpiperazin-1-yl)carbonyl]phenyl}-6-(5-fluoro-1H-indol-2-yl)pyrazin-2-amine, 2-{2-{[6-(5-fluoro-1H-indol-2-yl)pyrazin-2-yl]amino}-5-[(4-methylpiperazin-1-yl)carbonyl]phenoxy}-N,N-dimethylacetamide, N-{2-(2-ethoxyethoxy)-4-[(4-methylpiperazin-1-yl)carbonyl]phenyl}-6-(5-fluoro-1H-indol-2-yl)pyrazin-2-amine, N-{4-[(4-methylpiperazin-1-yl)carbonyl]phenyl}-6-(1H-pyrrolo[2,3-c]pyridin-2-yl)pyrazin-2-amine, N-(4-{[(3R)-3-(dimethylamino)pyrrolidin-1-yl]carbonyl}-2-methoxyphenyl)-6-(1H-pyrrolo[3,2-c]pyridin-2-yl)pyrazin-2-amine, N-{5-[(4-ethylpiperazin-1-yl)carbonyl]pyridin-2-yl}-6-(1H-indol-2-yl)pyrazin-2-amine, 6-(1H-indol-2-yl)-N-{5-[(4-methyl-1,4-diazepan-1-yl)carbonyl]pyridin-2-yl}pyrazin-2-amine, 6-(1H-indol-2-yl)-N-[5-(morpholin-4-ylcarbonyl)pyridin-2-yl]pyrazin-2-amine, 6-(5-fluoro-1H-indol-2-yl)-N-[6-(piperazin-1-ylcarbonyl)pyridin-3-yl]pyrazin-2-amine, N-{5-[(4-methyl-1,4-diazepan-1-yl)carbonyl]pyridin-2-yl}-6-(1H-pyrrolo[3,2-c]pyridin-2-yl)pyrazin-2-amine, N-[5-(5-fluoro-1H-indol-2-yl)pyridin-3-yl]-5-(piperazin-1-ylcarbonyl)pyridin-2-amine, 5-(1H-indol-2-yl)-N-{4-[(4-methylpiperazin-1-yl) carbonyl]phenyl}pyridin-3-amine, 5-(5-fluoro-1H-indol-2-yl)-N-[4-(piperazin-1-ylcarbonyl)phenyl]pyridin-3-amine, 5-(5-fluoro-1H-indol-2-yl)-N-{4-[(4-methyl-1,4-diazepan-1-yl)carbonyl]phenyl}pyridin-3-amine 5-(5-fluoro-1H-indol-2-yl)-N-[6-(piperazin-1-ylcarbonyl)pyridin-3-yl]pyridin-3-amine, and 4-[6-({4-[(4-methylpiperazin-1-yl)carbonyl]phenyl}amino)pyrazin-2-yl]benzamide, or a pharmaceutically acceptable salt or N-oxide thereof.
- Claim: 16. A pharmaceutical formulation comprising as an active ingredient a compound according to claim 1.
- Claim: 17. The pharmaceutical formulation of claim 16, further comprising a pharmaceutically acceptable diluent or carrier.
- Claim: 18. A method for the treatment or prophylaxis of a disorder related to undesired activity of MNK1 and/or MNK2 kinases, which comprises administering to a mammal in need of such treatment an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt or N-oxide thereof.
- Claim: 19. A method for the treatment or prophylaxis of a disorder selected from obesity, eating disorder, cachexia, diabetes mellitus, hypertension, coronary heart disease, hypercholesterolemia, dyslipidemia, hyperlipidemia, hyperglycemia, osteoarthritis, gallstones, sleep apnea, neurodegenerative disorders, cancer, inflammatory conditions, and type 2 diabetes, which comprises administering to a mammal in need of such treatment an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt or N-oxide thereof.
- Claim: 20. A method for the treatment or prophylaxis of type 2 diabetes, which comprises administering to a subject an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt or N-oxide thereof.
- Claim: 21. A method for the treatment or prophylaxis of an inflammatory condition, which comprises administering to a subject an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt or N-oxide thereof.
- Claim: 22. A method for the treatment or prophylaxis of cancer, which comprises administering to a subject an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt or N-oxide thereof.
- Claim: 23. A method for the treatment or prophylaxis of obesity, which comprises administering to a subject an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt or N-oxide thereof.
- Claim: 24. A method for reducing body-weight, comprising administering to a subject in need thereof an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt or N-oxide thereof.
- Current U.S. Class: 514227/800
- Current International Class: 61; 61; 61; 61; 61; 61; 07; 07; 07; 07; 07; 07; 07; 07; 07; 07; 61; 61; 61; 61
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