Claims for Patent: 8,895,601

Summary for Patent: 8,895,601

Title:	Pyrazolyl quinoxaline kinase inhibitors
Abstract:	The invention relates to new quinoxaline derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer. ##STR00001##
Inventor(s):	Saxty; Gordon (Cambridge, GB), Murray; Christopher William (Cambridge, GB), Berdini; Valerio (Cambridge, GB), Besong; Gilbert Ebai (Bad Duerkheim, DE), Hamlett; Christopher Charles Frederick (Cambridge, GB), Johnson; Christopher Norbert (Cambridge, GB), Woodhead; Steven John (San Diego, CA), Rees; David Charles (Cambridge, GB), Mevellec; Laurence Anne (Louviers, FR), Angibaud; Patrick Rene (Fontaine-Bellenger, FR), Freyne; Eddy Jean Edgard (Rumst, BE), Perera; Timothy Pietro Suren (Geel, BE), Gilissen; Ronaldus Arnodus Hendrika Joseph (Kasterlee, BE), Wroblowski; Berthold (Vosselaar, BE), Lacrampe; Jean Fernand Armand (Le Mesnil-Esnard, FR), Papanikos; Alexandra (Antwerp, BE), Querolle; Oliver Alexis Georges (Evreux, FR), Pasquier; Elisabeth Therese Jeanne (Le Neubourg, FR), Pilatte; Isabelle Noelle Constance (Louviers, FR), Bonnet; Pascal Ghislain Andre (Berchem, BE), Embrechts; Werner Constant Johan (Beerse, BE), Akkari; Rhalid (Vacquieres, FR), Meerpoel; Lieven (Beerse, BE)
Assignee:	Astex Therapeutics Ltd (Cambridge, GB)
Application Number:	13/643,741
Patent Claims:	1. A compound selected from the group consisting of a compound of formula (I) ##STR00663## a tautomeric form, stereochemically isomeric form and isotopic form thereof, wherein n is an integer represents an integer equal to 0, 1, 2, 3 or 4; R.sup.1 is hydrogen, C.sub.1-6alkyl, C.sub.2-4alkenyl, hydroxyC.sub.1-6alkyl, haloC.sub.1-6alkyl, hydroxyhaloC.sub.1-6alkyl, cyanoC.sub.1-4alkyl, C.sub.1-6alkoxyC.sub.1-6alkyl wherein each C.sub.1-6alkyl is optionally substituted with one or two hydroxyl groups, C.sub.1-6alkyl substituted with --NR.sup.4R.sup.5, C.sub.1-6alkyl substituted with --C(.dbd.O)--NR.sup.4R.sup.5, --S(.dbd.O).sub.2--C.sub.1-6alkyl, --S(.dbd.O).sub.2-haloC.sub.1-6alkyl, --S(.dbd.O).sub.2--NR.sup.14R.sup.15, C.sub.1-6alkyl substituted with --S(.dbd.O).sub.2--C.sub.1-6alkyl, C.sub.1-6alkyl substituted with --S(.dbd.O).sub.2-haloC.sub.1-6alkyl, C.sub.1-6alkyl substituted with --S(.dbd.O).sub.2--NR.sup.14R.sup.15, C.sub.1-6alkyl substituted with --NH--S(.dbd.O).sub.2--C.sub.1-6alkyl, C.sub.1-6alkyl substituted with --NH--S(.dbd.O).sub.2-haloC.sub.1-6alkyl, C.sub.1-6alkyl substituted with --NR.sup.12--S(.dbd.O).sub.2--NR.sup.14R.sup.15, R.sup.6, C.sub.1-6alkyl substituted with R.sup.6, C.sub.1-6alkyl substituted with --C(.dbd.O)--R.sup.6, hydroxyC.sub.1-6alkyl substituted with R.sup.6, C.sub.1-6alkyl substituted with --Si(CH.sub.3).sub.3, C.sub.1-6alkyl substituted with --P(.dbd.O)(OH).sub.2 or C.sub.1-6alkyl substituted with --P(.dbd.O)(OC.sub.1-6alkyl).sub.2; each R.sup.1a is independently selected from hydrogen, C.sub.1-4alkyl, hydroxyC.sub.1-4alkyl, C.sub.1-4alkyl substituted with amino or mono- or di(C.sub.1-4alkyl)amino or --NH(C.sub.3-8cycloalkyl), cyanoC.sub.1-4alkyl, C.sub.1-4alkoxyC.sub.1-4alkyl, and C.sub.1-4alkyl substituted with one or more fluoro atoms; each R.sup.2 is independently selected from hydroxyl, halogen, cyano, C.sub.1-4alkyl, C.sub.2-4alkenyl, C.sub.2-4alkynyl, C.sub.1-4alkoxy, hydroxyC.sub.1-4alkyl, hydroxyC.sub.1-4alkoxy, haloC.sub.1-4alkyl, haloC.sub.1-4alkoxy, hydroxyhaloC.sub.1-4alkyl, hydroxyhaloC.sub.1-4alkoxy, C.sub.1-4alkoxyC.sub.1-4alkyl, haloC.sub.1-4alkoxyC.sub.1-4alkyl, C.sub.1-4alkoxyC.sub.1-4alkyl wherein each C.sub.1-4alkyl is optionally substituted with one or two hydroxyl groups, hydroxyhaloC.sub.1-4alkoxyC.sub.1-4alkyl, R.sup.13, C.sub.1-4alkyl substituted with R.sup.13, C.sub.1-4alkyl substituted with --C(.dbd.O)--R.sup.13, C.sub.1-4alkoxy substituted with R.sup.13, C.sub.1-4alkoxy substituted with --C(.dbd.O)--R.sup.13, --C(.dbd.O)--R.sup.13, C.sub.1-4alkyl substituted with --NR.sup.7R.sup.8, C.sub.1-4alkyl substituted with --C(.dbd.O)--NR.sup.7R.sup.8, C.sub.1-4alkoxy substituted with --NR.sup.7R.sup.8, C.sub.1-4alkoxy substituted with --C(.dbd.O)--NR.sup.7R.sup.8, --NR.sup.7R.sup.8 and --C(.dbd.O)--NR.sup.7R.sup.8; or when two R.sup.2 groups are attached to adjacent carbon atoms they are optionally taken together to form a radical of formula: --O--(C(R.sup.17).sub.2).sub.p--O--; --X--CH.dbd.CH--; or --X--CH.dbd.N--; wherein R.sup.17 is hydrogen or fluorine, p is 1 or 2 and X is O or S; R.sup.3 is hydroxyl, C.sub.1-6alkoxy, hydroxyC.sub.1-6alkoxy, C.sub.1-6alkoxy substituted with --NR.sup.10R.sup.11, C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, haloC.sub.1-6alkyl optionally substituted with --O--C(.dbd.O)--C.sub.1-6alkyl, hydroxyC.sub.1-6alkyl optionally substituted with --O--C(.dbd.O)--C.sub.1-6alkyl, hydroxyC.sub.2-6alkenyl, hydroxyC.sub.2-6alkynyl, hydroxyhaloC.sub.1-6alkyl, cyanoC.sub.1-6alkyl, C.sub.1-6alkyl substituted with carboxyl, C.sub.1-6alkyl substituted with --C(.dbd.O)--C.sub.1-6alkyl, C.sub.1-6alkyl substituted with --C(.dbd.O)--O--C.sub.1-6alkyl, C.sub.1-6alkyl substituted with C.sub.1-6alkoxyC.sub.1-6alkyl-O--C(.dbd.O)--, C.sub.1-6alkyl substituted with C.sub.1-6alkoxyC.sub.1-6alkyl-C(.dbd.O)--, C.sub.1-6alkyl substituted with --O--C(.dbd.O)--C.sub.1-6alkyl, C.sub.1-6alkoxyC.sub.1-6alkyl wherein each C.sub.1-6alkyl is optionally substituted with one or two hydroxyl groups or with --O--C(.dbd.O)--C.sub.1-6alkyl, C.sub.2-6alkenyl substituted with C.sub.1-6alkoxy, C.sub.2-6alkynyl substituted with C.sub.1-6alkoxy, C.sub.1-6alkyl substituted with R.sup.9 and optionally substituted with --O--C(.dbd.O)--C.sub.1-6alkyl, C.sub.1-6alkyl substituted with --C(.dbd.O)--R.sup.9, C.sub.1-6alkyl substituted with hydroxyl and R.sup.9, C.sub.2-6alkenyl substituted with R.sup.9, C.sub.2-6alkynyl substituted with R.sup.9, C.sub.1-6alkyl substituted with --NR.sup.10R.sup.11, C.sub.2-6alkenyl substituted with --NR.sup.10R.sup.11, C.sub.2-6alkynyl substituted with --NR.sup.10R.sup.11, C.sub.1-6alkyl substituted with hydroxyl and --NR.sup.10R.sup.11, C.sub.1-6alkyl substituted with one or two halogens and --NR.sup.10R.sup.11, --C.sub.1-6alkyl-C(R.sup.12).dbd.N--O--R.sup.12, C.sub.1-6alkyl substituted with --C(.dbd.O)--NR.sup.10R.sup.11, C.sub.1-6alkyl substituted with --O--C(.dbd.O)--NR.sup.10R.sup.11, --S(.dbd.O).sub.2--C.sub.1-6alkyl, --S(.dbd.O).sub.2-haloC.sub.1-6alkyl, --S(.dbd.O).sub.2--NR.sup.14R.sup.15, C.sub.1-6alkyl substituted with --S(.dbd.O).sub.2--C.sub.1-6alkyl, C.sub.1-6alkyl substituted with --S(.dbd.O).sub.2-haloC.sub.1-6alkyl, C.sub.1-6alkyl substituted with --S(.dbd.O).sub.2--NR.sup.14R.sup.15, C.sub.1-6alkyl substituted with --NR.sup.12--S(.dbd.O).sub.2--C.sub.1-6alkyl, C.sub.1-6alkyl substituted with --NH--S(.dbd.O).sub.2-haloC.sub.1-6alkyl, C.sub.1-6alkyl substituted with --NR.sup.12--S(.dbd.O).sub.2--NR.sup.14R.sup.15, R.sup.13, C.sub.1-6alkyl substituted with --P(.dbd.O)(OH).sub.2 or C.sub.1-6alkyl substituted with --P(.dbd.O)(OC.sub.1-6alkyl).sub.2; R.sup.4 and R.sup.5 each independently hydrogen, C.sub.1-6alkyl, hydroxyC.sub.1-6alkyl, haloC.sub.1-6alkyl, hydroxyhaloC.sub.1-6alkyl, C.sub.1-6alkoxyC.sub.1-6alkyl wherein each C.sub.1-6alkyl is optionally substituted with one or two hydroxyl groups, --S(.dbd.O).sub.2--C.sub.1-6alkyl, --S(.dbd.O).sub.2-haloC.sub.1-6alkyl, --S(.dbd.O).sub.2--NR.sup.14R.sup.15, C.sub.1-6alkyl substituted with --S(.dbd.O).sub.2--C.sub.1-6alkyl, C.sub.1-6alkyl substituted with --S(.dbd.O).sub.2-haloC.sub.1-6alkyl, C.sub.1-6alkyl substituted with --S(.dbd.O).sub.2--NR.sup.14R.sup.15, C.sub.1-6alkyl substituted with --NH--S(.dbd.O).sub.2--C.sub.1-6alkyl, C.sub.1-6alkyl substituted with --NH--S(.dbd.O).sub.2-haloC.sub.1-6alkyl, C.sub.1-6alkyl substituted with --NH--S(.dbd.O).sub.2--NR.sup.14R.sup.15, R.sup.13 or C.sub.1-6alkyl substituted with R.sup.13; R.sup.6 is C.sub.3-8cycloalkyl, C.sub.3-8cycloalkenyl, phenyl, 4 to 7-membered monocyclic heterocyclyl containing at least one heteroatom selected from N, O and S; said C.sub.3-8cycloalkyl, C.sub.3-8cycloalkenyl, phenyl, 4 to 7-membered monocyclic heterocyclyl, each optionally and each independently being substituted by 1, 2, 3, 4 or 5 substituents, each substituent independently selected from cyano, C.sub.1-6alkyl, cyanoC.sub.1-6alkyl, hydroxyl, carboxyl, hydroxyC.sub.1-6alkyl, halogen, haloC.sub.1-6alkyl, hydroxyhaloC.sub.1-6alkyl, C.sub.1-6alkoxy, C.sub.1-6alkoxyC.sub.1-6alkyl, C.sub.1-6alkyl-O--C(.dbd.O)--, --NR.sup.14R.sup.15, --C(.dbd.O)--NR.sup.14R.sup.15, C.sub.1-6alkyl substituted with --NR.sup.14R.sup.15, C.sub.1-6alkyl substituted with --C(.dbd.O)--NR.sup.14R.sup.15, --S(.dbd.O).sub.2--C.sub.1-6alkyl, --S(.dbd.O).sub.2-haloC.sub.1-6alkyl, --S(.dbd.O).sub.2--NR.sup.14R.sup.15, C.sub.1-6alkyl substituted with --S(.dbd.O).sub.2--C.sub.1-6alkyl, C.sub.1-6alkyl substituted with --S(.dbd.O).sub.2-haloC.sub.1-6alkyl, C.sub.1-6alkyl substituted with --S(.dbd.O).sub.2--NR.sup.14R.sup.15, C.sub.1-6alkyl substituted with --NH--S(.dbd.O).sub.2--C.sub.1-6alkyl, C.sub.1-6alkyl substituted with --NH--S(.dbd.O).sub.2-haloC.sub.1-6alkyl and C.sub.1-6alkyl substituted with --NH--S(.dbd.O).sub.2--NR.sup.14R.sup.15; R.sup.7 and R.sup.8 each independently hydrogen, C.sub.1-6alkyl, hydroxyC.sub.1-6alkyl, haloC.sub.1-6alkyl, hydroxyhaloC.sub.1-6alkyl or C.sub.1-6alkoxyC.sub.1-6alkyl; R.sup.9 is C.sub.3-8cycloalkyl, C.sub.3-8cycloalkenyl, phenyl, naphthyl, or 3 to 12 membered monocyclic or bicyclic heterocyclyl containing at least one heteroatom selected from N, O and S, said C.sub.3-8cycloalkyl, C.sub.3-8cycloalkenyl, phenyl, naphthyl, or 3 to 12 membered monocyclic or bicyclic heterocyclyl each optionally and each independently substituted with 1, 2, 3, 4 or 5 substituents, each substituent independently selected from .dbd.O, C.sub.1-4alkyl, hydroxyl, carboxyl, hydroxyC.sub.1-4alkyl, cyano, cyanoC.sub.1-4alkyl, C.sub.1-4alkyl-O--C(.dbd.O)--, C.sub.1-4alkyl substituted with C.sub.1-4alkyl-O--C(.dbd.O)--, C.sub.1-4alkyl-C(.dbd.O)--, C.sub.1-4alkoxyC.sub.1-4alkyl wherein each C.sub.1-4alkyl is optionally substituted with one or two hydroxyl groups, halogen, haloC.sub.1-4alkyl, hydroxyhaloC.sub.1-4alkyl, --NR.sup.14R.sup.15, --C(.dbd.O)--NR.sup.14R.sup.15, C.sub.1-4alkyl substituted with --NR.sup.14R.sup.15, C.sub.1-4alkyl substituted with --C(.dbd.O)--NR.sup.14R.sup.15, C.sub.1-4alkoxy, --S(.dbd.O).sub.2--C.sub.1-4alkyl, --S(.dbd.O).sub.2-haloC.sub.1-4alkyl, --S(.dbd.O).sub.2--NR.sup.14R.sup.15, C.sub.1-4alkyl substituted with --S(.dbd.O).sub.2--NR.sup.14R.sup.15, C.sub.1-4alkyl substituted with --NH--S(.dbd.O).sub.2--C.sub.1-4alkyl, C.sub.1-4alkyl substituted with --NH--S(.dbd.O).sub.2-haloC.sub.1-4alkyl, C.sub.1-4alkyl substituted with --NH--S(.dbd.O).sub.2--NR.sup.14R.sup.15, R.sup.13, --C(.dbd.O)--R.sup.13, C.sub.1-4alkyl substituted with R.sup.13, phenyl optionally substituted with R.sup.16, phenylC.sub.1-6alkyl wherein the phenyl is optionally substituted with R.sup.16, and a 5 or 6-membered aromatic monocyclic heterocyclyl containing at least one heteroatom selected from N, O and S wherein said heterocyclyl is optionally substituted with R.sup.16; or when two of the substituents of R.sup.9 are attached to the same atom, they are optionally taken together to form a 4 to 7-membered saturated monocyclic heterocyclyl containing at least one heteroatom selected from N, O and S; R.sup.10 and R.sup.11 are each independently hydrogen, carboxyl, C.sub.1-6alkyl, cyanoC.sub.1-6alkyl, C.sub.1-6alkyl substituted with --NR.sup.14R.sup.15, C.sub.1-6alkyl substituted with --C(.dbd.O)--NR.sup.14R.sup.15, haloC.sub.1-6alkyl, hydroxyC.sub.1-6alkyl, hydroxyhaloC.sub.1-6alkyl, C.sub.1-6alkoxy, C.sub.1-6alkoxyC.sub.1-6alkyl wherein each C.sub.1-6alkyl is optionally substituted with one or two hydroxyl groups, R.sup.6, C.sub.1-6alkyl substituted with R.sup.6, --C(.dbd.O)--R.sup.6, --C(.dbd.O)--C.sub.1-6alkyl, --C(.dbd.O)-hydroxyC.sub.1-6alkyl, --C(.dbd.O)-haloC.sub.1-6alkyl, --C(.dbd.O)-hydroxyhaloC.sub.1-6alkyl, C.sub.1-6alkyl substituted with --Si(CH.sub.3).sub.3, --S(.dbd.O).sub.2--C.sub.1-6alkyl, --S(.dbd.O).sub.2-haloC.sub.1-6alkyl, --S(.dbd.O).sub.2--NR.sup.14R.sup.15, C.sub.1-6alkyl substituted with --S(.dbd.O).sub.2--C.sub.1-6alkyl, C.sub.1-6alkyl substituted with --S(.dbd.O).sub.2-haloC.sub.1-6alkyl, C.sub.1-6alkyl substituted with --S(.dbd.O).sub.2--NR.sup.14R.sup.15, C.sub.1-6alkyl substituted with --NH--S(.dbd.O).sub.2--C.sub.1-6alkyl, C.sub.1-6alkyl substituted with --NH--S(.dbd.O).sub.2-haloC.sub.1-6alkyl or C.sub.1-6alkyl substituted with --NH--S(.dbd.O).sub.2--NR.sup.14R.sup.15; R.sup.12 is hydrogen or C.sub.1-4alkyl optionally substituted with C.sub.1-4alkoxy; R.sup.13 is C.sub.3-8cycloalkyl or a saturated 4 to 6-membered monocyclic heterocyclyl containing at least one heteroatom selected from N, O and S, wherein said C.sub.3-8cycloalkyl or monocyclic heterocyclyl is optionally substituted with 1, 2 or 3 substituents each independently selected from halogen, hydroxyl, C.sub.1-6alkyl, --C(.dbd.O)--C.sub.1-6alkyl, C.sub.1-6alkoxy, and --NR.sup.14R.sup.15; R.sup.14 and R.sup.15 are each independently hydrogen, or haloC.sub.1-4alkyl,or C.sub.1-4alkyl optionally substituted with a substituent selected from hydroxyl, C.sub.1-4alkoxy, amino and mono- or di(C.sub.1-4alkyl)amino; and R.sup.16 is hydroxyl, halogen, cyano, C.sub.1-4alkyl, C.sub.1-4alkoxy, --NR.sup.14R.sup.15 or --C(.dbd.O)NR.sup.14R.sup.15; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 2. A compound according to claim 1 wherein R.sup.1 is hydrogen, C.sub.1-6alkyl, hydroxyC.sub.1-6alkyl, haloC.sub.1-6alkyl, C.sub.1-6alkoxyC.sub.1-6alkyl wherein each C.sub.1-6alkyl is optionally substituted with one or two hydroxyl groups, C.sub.1-6alkyl substituted with --NR.sup.4R.sup.5, C.sub.1-6alkyl substituted with --C(.dbd.O)--NR.sup.4R.sup.5, --S(.dbd.O).sub.2--C.sub.1-6alkyl, --S(.dbd.O).sub.2--NR.sup.14R.sup.15, C.sub.1-6alkyl substituted with --S(.dbd.O).sub.2--C.sub.1-6alkyl, C.sub.1-6alkyl substituted with --NH--S(.dbd.O).sub.2--C.sub.1-6alkyl, R.sup.6, C.sub.1-6alkyl substituted with R.sup.6, C.sub.1-6alkyl substituted with --C(.dbd.O)--R.sup.6, hydroxyC.sub.1-6alkyl substituted with R.sup.6, or C.sub.1-6alkyl substituted with --Si(CH.sub.3).sub.3; each R.sup.1a is hydrogen; R.sup.10 and R.sup.11 are each independently hydrogen, C.sub.1-6alkyl, cyanoC.sub.1-6alkyl, C.sub.1-6alkyl substituted with --NR.sup.14R.sup.15, C.sub.1-6alkyl substituted with --C(.dbd.O)--NR.sup.14R.sup.15, haloC.sub.1-6alkyl, hydroxyC.sub.1-6alkyl, hydroxyhaloC.sub.1-6alkyl, C.sub.1-6alkoxy, C.sub.1-6alkoxyC.sub.1-6alkyl wherein each C.sub.1-6alkyl is optionally substituted with one or two hydroxyl groups, R.sup.6, C.sub.1-6alkyl substituted with R.sup.6, --C(.dbd.O)--R.sup.6, --C(.dbd.O)--C.sub.1-6alkyl, --C(.dbd.O)-hydroxyC.sub.1-6alkyl, --C(.dbd.O)-haloC.sub.1-6alkyl, --C(.dbd.O)-hydroxyhaloC.sub.1-6alkyl, C.sub.1-6alkyl substituted with --Si(CH.sub.3).sub.3, --S(.dbd.O).sub.2--C.sub.1-6alkyl, --S(.dbd.O).sub.2-haloC.sub.1-6alkyl, --S(.dbd.O).sub.2--NR.sup.14R.sup.15, C.sub.1-6alkyl substituted with --S(.dbd.O).sub.2--C.sub.1-6alkyl, C.sub.1-6alkyl substituted with --S(.dbd.O).sub.2-haloC.sub.1-6alkyl, C.sub.1-6alkyl substituted with --S(.dbd.O).sub.2--NR.sup.14R.sup.15, C.sub.1-6alkyl substituted with --NH--S(.dbd.O).sub.2--C.sub.1-6alkyl, C.sub.1-6alkyl substituted with --NH--S(.dbd.O).sub.2-haloC.sub.1-6alkyl or C.sub.1-6alkyl substituted with --NH--S(.dbd.O).sub.2--NR.sup.14R.sup.15; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 3. A compound according to claim 1 wherein each R.sup.1a is hydrogen; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 4. A compound according to claim 1 wherein R.sup.1 is C.sub.1-6alkyl; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 5. A compound according to claim 1 wherein R.sup.1 is CH.sub.3-- or CD.sub.3-; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 6. A compound according to claim 1 wherein R.sup.2 is independently selected from halogen, cyano, C.sub.1-4alkyl, C.sub.2-4alkenyl, C.sub.1-4alkoxy, hydroxyC.sub.1-4alkyl, hydroxyC.sub.1-4alkoxy, haloC.sub.1-4alkoxy, C.sub.1-4alkoxyC.sub.1-4alkyl, R.sup.13, C.sub.1-4alkoxy substituted with R.sup.13, --C(.dbd.O)--R.sup.13, C.sub.1-4alkyl substituted with NR.sup.7R.sup.8, C.sub.1-4alkoxy substituted with NR.sup.7R.sup.8, --NR.sup.7R.sup.8 and --C(.dbd.O)--NR.sup.7R.sup.8; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 7. A compound according to claim 6 wherein R.sup.2 is C.sub.1-4alkyloxy; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 8. A compound according to claim 6 wherein R.sup.2 is CH.sub.3O-- or CD.sub.3O--; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 9. A compound according to claim 1 wherein R.sup.3 is C.sub.1-6alkyl, hydroxyC.sub.1-6alkyl, hydroxyhaloC.sub.1-6alkyl, haloC.sub.1-6alkyl, C.sub.1-6alkyl substituted with --C(.dbd.O)--C.sub.1-6alkyl, C.sub.1-6alkoxyC.sub.1-6alkyl wherein each C.sub.1-6alkyl is optionally substituted with one or two hydroxyl groups, C.sub.1-6alkyl substituted with R.sup.9, C.sub.1-6alkyl substituted with --NR.sup.10R.sup.11, C.sub.1-6alkyl substituted with hydroxyl and --NR.sup.10R.sup.11, C.sub.1-6alkyl substituted with one or two halogens and --NR.sup.10R.sup.11, C.sub.1-6alkyl substituted with --C(.dbd.O)--O--C.sub.1-6alkyl, C.sub.1-6alkyl substituted with --O--C(.dbd.O)--NR.sup.10R.sup.11, C.sub.1-6alkyl substituted with carboxyl, C.sub.1-6alkyl substituted with --NR.sup.12--S(.dbd.O).sub.2--C.sub.1-6alkyl, C.sub.1-6alkyl substituted with --NR.sup.12--S(.dbd.O).sub.2--NR.sup.14R.sup.15, C.sub.1-6alkyl substituted with hydroxyl and R.sup.9, --C.sub.1-6alkyl-C(R.sup.12).dbd.N--O--R.sup.12, C.sub.1-6alkyl substituted with --C(.dbd.O)--NR.sup.10R.sup.11, C.sub.1-6alkyl substituted with --C(.dbd.O)--R.sup.9, C.sub.2-6alkynyl substituted with R.sup.9, hydroxyC.sub.1-6alkoxy, C.sub.2-6alkenyl, C.sub.2-6alkynyl or R.sup.13; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 10. A compound according to claim 1 wherein R.sup.1 is C.sub.1-6alkyl, each R.sup.1a is hydrogen, n is an integer equal to 2, each R.sup.2 is C.sub.1-4alkoxy, and R.sup.3 is C.sub.1-6alkyl substituted with --NR.sup.10R.sup.11; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 11. A compound according to claim 10 wherein R.sup.10 is hydrogen or C.sub.1-6alkyl, and R.sup.11 is hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, --C(.dbd.O)--C.sub.1-6alkyl, --S(.dbd.O).sub.2--C.sub.1-6alkyl, --S(.dbd.O).sub.2--NR.sup.14R.sup.15, hydroxyC.sub.1-6alkyl, --C(.dbd.O)-hydroxyhaloC.sub.1-6alkyl, --C(.dbd.O)--R.sup.6, cyanoC.sub.1-6alkyl, R.sup.6, C.sub.1-6alkyl substituted with R.sup.6, --C(.dbd.O)-haloC.sub.1-6alkyl, or C.sub.1-6alkyl substituted with --Si(CH.sub.3).sub.3; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 12. A compound according to claim 10 wherein R.sup.10 is hydrogen, --CH.sub.3, --CH.sub.2CH.sub.3 or --CH(CH.sub.3).sub.2 and R.sup.11 is hydrogen, --CH.sub.3, --CH.sub.2CH.sub.3, --CH(CH.sub.3).sub.2, --CH.sub.2CF.sub.3, --CH.sub.2CHF.sub.2, --CH.sub.2CH.sub.2F, --C(.dbd.O)--CH.sub.3, --S(.dbd.O).sub.2--CH.sub.3, --S(.dbd.O).sub.2--CH.sub.2CH.sub.3, --S(.dbd.O).sub.2--CH(CH.sub.3).sub.2, --S(.dbd.O).sub.2--N(CH.sub.3).sub.2, --CH.sub.2CH.sub.2OH, --C(.dbd.O)--C(OH)(CH.sub.3)CF.sub.3, --C(.dbd.O)-cyclopropyl, --CH.sub.2CH.sub.2CN, cyclopropane, cyclopentane, 2,2,6,6-tetramethyl-piperidine, --CH.sub.2C.sub.3H.sub.5, --CH.sub.2-tetrahydrofuran, --C(.dbd.O)-(1-methyl-piperidin-3-yl), --C(.dbd.O)--CF.sub.3, --CH.sub.2Si(CH.sub.3).sub.3, or --CH.sub.2--C.sub.6H.sub.5; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 13. A compound according to claim 10 wherein R.sup.1 is --CH.sub.3, each R.sup.1a is hydrogen, n is an integer equal to 2, each R.sup.2 is CH.sub.3O--, and R.sup.3 is --CH.sub.2CH.sub.2NHCH(CH.sub.3).sub.2; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 14. A compound according to claim 10 wherein R.sup.1 is --CH.sub.3, each R.sup.1a is hydrogen, n is an integer equal to 2, each R.sup.2 is CH.sub.3O--, R.sup.3 is --CH.sub.2CH.sub.2--CH.sub.2--NHCH.sub.2CF.sub.3; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 15. A compound according to claim 10 wherein R.sup.1 is --CH.sub.3, each R.sup.1a is hydrogen, n is an integer equal to 2, each R.sup.2 is CH.sub.3O--, R.sup.3 is --CH.sub.2CH.sub.2NH.sub.2; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 16. A compound according to claim 1 wherein the compound is N-(3,5-dimethoxyphenyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]-N- '-(2,2,2-trifluoroethyl)propane-1,3-diamine; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 17. The compound N-(3,5-dimethoxyphenyl)-N'-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4-yl- )quinoxalin-6-yl]ethane-1,2-diamine; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 18. A compound according to claim 1 wherein the compound is N-(3,5-dimethoxyphenyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]et- hane-1,2-diamine; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 19. A combination comprising a compound according to claim 1; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof, and another anticancer agent. 20. A combination according to claim 19, wherein the compound is selected from: N-(3,5-dimethoxyphenyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6- -yl]-N'-(2,2,2-trifluoroethyl)propane-1,3-diamine; N-(3,5-dimethoxyphenyl)-N'-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4-yl- )quinoxalin-6-yl]ethane-1,2-diamine; and N-(3,5-dimethoxyphenyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]et- hane-1,2-diamine; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 21. A pharmaceutical composition comprising a compound according to claim 1; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof, and a pharmaceutically acceptable carrier. 22. A pharmaceutical composition comprising a compound according to claim 16, or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof, and a pharmaceutically acceptable carrier. 23. A pharmaceutical composition comprising a compound according to claim 17; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof, and a pharmaceutically acceptable carrier. 24. A pharmaceutical composition comprising a compound according to claim 18, or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof, and a pharmaceutically acceptable carrier. 25. A combination according to claim 19, wherein the anticancer agent is A kinase inhibitor. 26. A compound according to claim 16 wherein the compound is N-(3,5-dimethoxyphenyl)-N- [3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]-N'-(2,2,2-trifluoroethyl)pr- opane-1,3-diamine. 27. A compound according to claim 17 wherein the compound is N-(3,5-dimethoxyphenyl)-N'-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4-yl- )quinoxalin-6-yl]ethane-1,2-diamine. 28. A compound according to claim 18 wherein the compound is N-(3,5-dimethoxyphenyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]et- hane-1,2-diamine. 29. A combination according to claim 20, wherein the compound is selected from: N-(3,5-dimethoxyphenyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6- -yl]-N'-(2,2,2-trifluoroethyl)propane-1,3-diamine; N-(3,5-dimethoxyphenyl)-N'-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4- yl)quinoxalin-6-yl]ethane-1,2-diamine; and N-(3,5-dimethoxyphenyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]et- hane-1,2-diamine. 30. A combination according to claim 20, where the anticancer agent is a kinase inhibitor. 31. A combination according to claim 29, where the anticancer agent is a kinase inhibitor. 32. A pharmaceutical composition comprising a compound according to claim 26, and a pharmaceutically acceptable carrier. 33. A pharmaceutical composition comprising a compound according to claim 27, and a pharmaceutically accepatable carrier. 34. A pharmaceutical composition comprising a compound according to claim 28, and a pharmaceutically accepatable carrier. 35. A combination according to claim 20, wherein the compound is N-(3,5-dimethoxyphenyl)-N'-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4-yl- )quinoxalin-6-yl]ethane-1,2-diamine. 36. A combination according to claim 35, where the anticancer agent is a kinase inhibitor.