Claims for Patent: 9,464,071
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Summary for Patent: 9,464,071
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. |
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), Reader; Michael (Bishop's Stortford, GB), Rees; David Charles (Cambridge, GB), Mevellec; Laurence Anne (Louviers, FR), Angibaud; Patrick Rene (Fontaine-Bellenger, FR), Freyne; Eddy Jean Edgard (Rumst, BE), Govaerts; Tom Cornelis Hortense (Betekom, BE), Weerts; Johan Erwin Edmond (Beerse, 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; Olivier 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: | 14/505,020 |
Patent Claims: |
1. A method for treating a subject suffering from a disease state or condition mediated by a FGFR kinase, said method comprising administering to the subject a
compound selected from the group consisting of a compound of formula (I) ##STR00707## a tautomeric form, stereochemically isomeric form and isotopic form thereof, wherein n is 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 are 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 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 are 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 method according to claim 1, wherein the compound is selected from the group consisting of a compound of formula (I), a tautomeric form, stereochemically isomeric form and isotopic form thereof, 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 method according to claim 1, wherein the compound is selected from the group consisting of a compound of formula (I), a tautomeric form, stereochemically isomeric form and isotopic form thereof, wherein each R.sup.1a is hydrogen; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 4. A method according to claim 1, wherein the compound is selected from the group consisting of a compound of formula (I), a tautomeric form, stereochemically isomeric form and isotopic form thereof, 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 method according to claim 1, wherein the compound is selected from the group consisting of a compound of formula (I), a tautomeric form, stereochemically isomeric form and isotopic form thereof, 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 method according to claim 1, wherein the compound is selected from the group consisting of a compound of formula (I), a tautomeric form, stereochemically isomeric form and isotopic form thereof, 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 method according to claim 6, wherein the compound is selected from the group consisting of a compound of formula (I), a tautomeric form, stereochemically isomeric form and isotopic form thereof, wherein R.sup.2 is C.sub.1-4alkoxy; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 8. A method according to claim 6, wherein the compound is selected from the group consisting of a compound of formula (I), a tautomeric form, stereochemically isomeric form and isotopic form thereof, 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 method according to claim 1, wherein the compound is selected from the group consisting of a compound of formula (I), a tautomeric form, stereochemically isomeric form and isotopic form thereof, 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 method according to claim 1, wherein the compound is selected from the group consisting of a compound of formula (I), a tautomeric form, stereochemically isomeric form and isotopic form thereof, 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 method according to claim 10, wherein the compound is selected from the group consisting of a compound of formula (I), a tautomeric form, stereochemically isomeric form and isotopic form thereof, 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. 12. A method according to claim 10, wherein the compound is selected from the group consisting of a compound of formula (I), a tautomeric form, stereochemically isomeric form and isotopic form thereof, 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. 13. A method according to claim 10, wherein the compound is selected from the group consisting of a compound of formula (I), a tautomeric form, stereochemically isomeric form and isotopic form thereof, 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.2--CH.sub.2--NHCH.sub.2CF.sub.3 or --CH.sub.2--CH.sub.2NH.sub.2; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 14. A method according to claim 1, 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; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 15. A method according to claim 14, 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. 16. A method according to claim 1, 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; 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. 17. A method according to claim 16, 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; and N-(3,5-dimethoxyphenyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]et- hane-1,2-diamine. 18. A method for treating a subject suffering from cancer, said method comprising administering to the subject a compound selected from the group consisting of a compound of formula (I) ##STR00708## a tautomeric form, stereochemically isomeric form and isotopic form thereof, wherein n is 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.11R.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 are 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 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 are 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.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. 19. A method according to claim 18, wherein the cancer is selected from multiple myeloma, myeloproliferative disorders, endometrial cancer, prostate cancer, bladder cancer, lung cancer, ovarian cancer, breast cancer, gastric cancer, colorectal cancer, and oral squamous cell carcinoma. 20. A method according to claim 18, wherein the cancer is selected from lung cancer, squamous cell carcinoma, liver cancer, kidney cancer, breast cancer, colon cancer, colorectal cancer, and prostate cancer. 21. A method according to claim 19, wherein the cancer is multiple myeloma. 22. A method according to claim 21, wherein the cancer is t(4;14) translocation positive multiple myeloma. 23. A method according to claim 19, wherein the cancer is bladder cancer. 24. A method according to claim 23, wherein the cancer is bladder cancer with a FGFR3 chromosomal translocation. 25. A method according to claim 23, wherein the cancer is bladder cancer with a FGFR3 point mutation. 26. A method according to claim 18, wherein the cancer is a tumor with a mutant of FGFR1, FGFR2, FGFR3 or FGFR4. 27. A method according to claim 18, wherein the cancer is a tumor with a gain-of-function mutant of FGFR2 or FGFR3. 28. A method according to claim 18, wherein the cancer is a tumor with over-expression of FGFR1. 29. A method according to claim 18, wherein the cancer is urothelial carcinoma. 30. A method according to claim 18, 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; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 31. A method according to claim 30, 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. 32. A method according to claim 18, 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; 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. 33. A method for treating a subject suffering from a carcinoma, wherein the carcinoma is selected from a carcinoma of the bladder, breast, colon, kidney, epidermis, liver, lung, oesophagus, head and neck, gall bladder, ovary, pancreas, stomach, gastrointestinal (also known as gastric) cancer, cervix, endometrium, thyroid, prostate, or skin, a hematopoietic tumour of lymphoid lineage; a hematopoietic tumour of myeloid lineage; multiple myeloma; thyroid follicular cancer; a tumour of mesenchymal origin; a tumour of the central or peripheral nervous system; melanoma; seminoma; teratocarcinoma; osteosarcoma; xeroderma pigmentosum; keratoctanthoma; or Kaposi's sarcoma, said method comprising administering to the subject a compound selected from the group consisting of a compound of formula (I) ##STR00709## a tautomeric form, stereochemically isomeric form and isotopic form thereof, wherein n is 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.11R.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 are 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 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 are 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.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. 34. A method according to claim 33, wherein the carcinoma is glioblastoma multiforme. 35. A method according to claim 33, 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; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 36. A method according to claim 35, 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. 37. A method of inhibiting a FGFR kinase, which method comprises contacting the kinase with a kinase-inhibiting compound selected from the group consisting of a compound of formula (I) ##STR00710## a tautomeric form, stereochemically isomeric form and isotopic form thereof, wherein n is 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 are 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 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 are 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.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. 38. A method according to claim 37, 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; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 39. A method according to claim 38, 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. 40. A method according to claim 1, further comprising administering to the subject one or more other anticancer agents. 41. A method according to claim 40, wherein the one or more other anticancer agents comprises a kinase inhibitor. 42. A method according to claim 40, 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; or an N-oxide thereof, a pharmaceutically acceptable salt thereof or a solvate thereof. 43. A method according to claim 42, 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. 44. A method according to claim 20 wherein the lung cancer is NSCLC. 45. A method according to claim 33 wherein the carcinoma is adenocarcinoma of the lung, small cell lung cancer or non-small cell lung carcinoma. |
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