Title of Invention

"A COMPOUND,OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME"

Abstract

A compound, or pharmaceutically acceptable salt thereof, which is selected from the following: [4-(3-Amino-phenyI)-pyrimidin-2-yl]-[4-(2-methoxy-ethoxy)-phenyl]-amine [3]; [4-(3-Amino-phenyl)-pyrimidine-2-yl]-(3-nitro-phenyl)-amine [19]; [4-(3-Ethylamino-phenyl)-pyrimidine-2-yl]-(4-methoxy-phenyl)-amine [25]; (3-Nitro-phenyl)-[4-(3-[l,2,4]triazol-l-ylmethyl-phenyl)-pyrimidin-2-yl]-amine [30]; 3-[4-(3[ 1,2,4]Triazol-l-ylmethyl-phenyl)-pyrimidin-2-ylamino]-benzonitrile [36]; N-{3-[2-(3-Nitro-phenylamino)-pyrimidin-4-yl]-benzy}-methanesulfonamide [40]; (4-{3-[(Ethyl-isopropyl-amino)-methyl]-phenyl}-pyrimidine-2-yl)-(3-nitro-phenyl)-amine [46]; (4-{3-[(Ethyl-isopropyl-amino)-methyl]-phenyl}-pyrimidine-2-yl)-(6-methoxy-pyridin-3-yl)-amine [53]; {4[3-(4-Methyl-piperazin-1 -ylmethyl) -phenyl]-pyrimidin-2-yl}-(3-nitro-phenyl)-amine [54].

Full Text

The present invention relates to a compound, or pharmaceutically acceptable salt thereof and pharmaceutical composition comprising the same. The present invention relates to substituted pyrimidine derivatives. In particular, the invention relates to [4-(3-substituted-phenyl)-pyrimidin-2-yl]-phenyl-amines and [4-(3-substituted-phenyl)-pyrimidin-2-yl]-(pyridine-3-yl)-amines and their use in therapy. More specifically, but not exclusively, the invention relates to compounds that are capable of inhibiting one or more protein kinases. BACKGROUND TO THE INVENTION In eukaryotes, all biological functions, including DNA replication, cell cycle progression, energy metabolism, and cell growth and differentiation, are regulated through the reversible phosphorylation of proteins. The phosphorylation state of a protein determines not only its function, subcellular distribution, and stability, but also what other proteins or cellular components it associates with. The balance of specific phosphorylation in the proteome as a whole, as well as of individual members in a biochemical pathway, is thus used by organisms as a strategy to maintain homeostasis in response to an ever-changing environment. The enzymes that carry out these phosphorylation and dephosphorylation steps are protein kinases and phosphatases, respectively. The eukaryotic protein kinase family is one of the largest in the human genome, comprising some 500 genes [1,2]. The majority of kinases contain a 250-300 amino acid residue catalytic domain with a conserved core structure. This domain comprises a blading pocket for ATP (less frequently GTP), whose terminal phosphate group the kinase transfers covalently to its macromolecular substrates. The phosphate donor is always bound as a complex with a divalent ion (usually Mg2+or Mn2+). Another important function of the catalytic domain is the binding and orientation for phosphotransfer of the macromolecular substrate. The catalytic domains present in most kinases are more or less homologous. A wide variety of molecules capable of inhibiting protein kinase function through antagonising ATP binding are known in the art [3-7]. By way of example, the applicant has previously disclosed 2-anihno^-heteroaryl-pyrimidine compounds with kinase inhibitory properties, particularly against cyclin-dependent kinases (CDKs) [8-12]. CDKs are serine/threonine protein kinases that associate with various cyclin subunits. These complexes are important for the regulation of eukaryotic cell cycle progression, but also for the regulation of transcription [13,14]. The present invention seeks to provide [4-(3-substituted-phenyl)-pyrimidin-2-yl]-phenylamines and [4-(3-substituted-phenyl)-pyrmii6^-2-yl]-(pyridine-3-yl)-amines. More specifically, the invention relates to compounds that have broad therapeutic applications in the treatment of a number of different diseases and/or that are capable of inhibiting one or more protein kinases. STATEMENT OF INVENTION A first aspect of the invention relates to compounds of formula I, or pharmaceutically acceptable salts thereof, (Figure Removed) wherein: ZisCR10orN; , one of R1 and R2 is selected from (CH2)raR11, (CH2)mR12, (CH2)mNR12R13, (CH2)mOR12, (CH2)mNR13CO(CH2)nRn, (CH2)mNR13COR12, (CH2)mCONR13(CH2)nRn, (CH2)mCONR12R13, (CH2)mCO(CH2)nRn and (CH2)mCOR12; where m is 0,1, 2,3 or 4 and nisi, 2,3 or 4; the other of R1 and R2 is H or R1 *; R3 and R5 are both H; R4isHorRu; R6 is H or (CH-OpR11, where p is 0 or 1; R7, R9 and R10 are each independently H or R1 ]; R8 is selected from H, halogen, N02) CN, OR13, NR13R14, NHCOR13, CF3, COR13, R13, CONR13R15, SO2NR13R14, S02R13, NR!3SO2R14, OCH2CH2OH3 OCH2CH2OMe, morpholino, piperidinyl, and piperazinyl; each R11 is independently halogen, NO2, CN, (CH2)qOR13, (CH2)rNR13R14, NHCOR13, CF3, COR13, R13, CONR13R14, S02NR13R14, SO2R13, OR12, NR13SO2R14 S OCH2CH2OH, OCH2CH2OMe, NR^SOjR12, (CH2)SNR12R13, morpholino, piperidinyl or piperazinyl, where q, r and s are each independently 0,1,2,3 or 4; each R12 is independently a hydrocarbyl group optionally containing one or more heteroatoms and optionally substituted with one or more R11 groups; each R13 and each R14 is independently H or an alkyl group; and R15 is an alkyl group; providing that when - Z is CR10 and R9 is H, at least one of R7, R8 and R10is otherthan OMe; and - Z is CR10 and R7'9 are all H, R10 is other than OCF2CHF2. A second aspect of the invention relates to a pharmaceutical composition comprising a compound of formula I as defined above admixed with a pharmaceutically acceptable diluent, excipient or carrier. Further aspects of the invention relate to the use of compounds of formula I as defined above in the preparation of a medicament for treating one or more of the following: 4 a proliferative disorder; a viral disorder; a CNS disorder; a stroke; alopecia; and diabetes. Another aspect of the invention relates to the use of compounds of formula I as defined above in an assay for identifying further candidate compounds capable of inhibiting one or more of a cyclin dependent kinase, GSK, aurora kinase and a PLK enzyme. DETAILED DESCRIPTION As used herein, the term "hydrocarbyl" refers to a group comprising at least C and H. If the hydrocarbyl group comprises more than one C then those carbons need not necessarily be linked to each other. For example, at least two of the carbons may be linked via a suitable element or group. Thus, the hydrocarbyl group may contain heteroatoms. Suitable heteroatoms will be apparent to those skilled in the art and include, for instance, sulphur, nitrogen, oxygen, phosphorus and silicon. Where the hydrocarbyl group contains one or more heteroatoms, the group may be linked via a carbon atom or via a heteroatom to another group, i.e. the linker atom may be a carbon or a heteroatom. Preferably, the hydrocarbyl group is an aryl, heteroaryl, alkyl, cycloalkyl, aralkyl, alicyclic, heteroalicyclic or alkenyl group. More preferably, the hydrocarbyl group is an aryl, heteroaryl, alkyl, cycloalkyl, aralkyl or alkenyl group. The hydrocarbyl group may be optionally substituted by one or more R11 groups. As used herein, the term "alkyl" includes both saturated straight chain and branched alkyl groups which may be substituted (mono- or poly-) or unsubstituted. Preferably, the alkyl group is a €1-20 alkyl group, more preferably a CMS, more preferably still a CMZ alkyl group, more preferably still, a Ci-e alkyl group, more preferably a Ci-3 alkyl group. Particularly preferred alkyl groups include, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl and hexyl. Suitable substituents include, for example, one or more R11 groups. Preferably, the alkyl group is unsubstituted. As used herein, the term "cycloalkyl" refers to a cyclic alkyl group which may be substituted (mono- or poly-) or unsubstituted. Preferably, the cycloalkyl group is a €3-12 cycloalkyl group. Suitable substituents include, for example, one or more Rn groups. As used herein, the term "alkenyl" refers to a group containing one or more carbon-carbon double bonds, which may be branched or unbranched, substituted (mono- or poly-) or unsubstituted. Preferably the alkenyl group is a 02-20 alkenyl group, more preferably a C2. 15 alkenyl group, more preferably still a Cz-iz alkenyl group, or preferably a C2-6 alkenyl group, more preferably a €2-3 alkenyl group. Suitable substituents include, for example, one or more R11 groups as defined above. As used herein, the term "aryl" refers to a €5-12 aromatic group which may be substituted (mono- or poly-) or unsubstituted. Typical examples include phenyl and naphthyl etc. Suitable substituents include, for example, one or more Ru groups. As used herein, the term "heteroaryl" refers to a Ca-n aromatic, substituted (mono- or poly- ) or unsubstituted group, which comprises one or more heteroatoms. Preferably, the heteroaryl group is a €4.12 aromatic group comprising one or more heteroatoms selected from N, O and S. Suitable heteroaryl groups include pyrrole, pyrazole, pyrimidine, pyrazine, pyridine, quinoline, thiophene, 1,2,3-triazole, 1,2,4-triazole, thiazole, oxazole, iso-thiazole, iso-oxazole, imidazole, furan and the like. Again, suitable substituents include, for example, one or more R11 groups. As used herein, the term "alicyclic" refers to a cyclic aliphatic group which optionally contains one or more heteroatoms. Preferred alicyclic groups include piperidinyl, pyrrolidinyl, piperazinyl and morpholino. More preferably, the alicyclic group is selected from N-piperidinyl, N-pyrrolidinyl, N-piperazinyl and N-morpholino As used herein, the term "aralkyl" includes, but is not limited to, a group having both aryl and alkyl functionalities. By way of example, the term includes groups in which one of the hydrogen atoms of the alkyl group is replaced by an aryl group, e.g. a phenyl group optionally having one or more substituents such as halo, alkyl, alkoxy, hydroxy, and the like. Typical aralkyl groups include benzyl, phenethyl and the like. One preferred embodiment of the invention relates to compounds of formula la, or pharmaceutically acceptable salts thereof, ,2 la wherein: ZisCR10orN; Rl is selected from (CH2)mR11, (CHyjR.12, (CH2)mNR12R13, (CH2)mOR12, (CH2)mNR13CO(CH2)nR11 ) (CH2)mNRl3COR12, (CH2)mCONR13(CH2)nRn, (CH2)mCONR12R13, (CH2)raCO(CH2)nRu and (CH2)mCOR12; where m is 0,1,2, 3 or 4 and nis 1,2, 3 or 4; R3 and R5 are both H; R2 and R4 are each independently H or R1!; R6 is H or (CH2)pRn, where p is 0 or 1; R7, R9 and R10 are each independently H or R11; R8 is selected from H, halogen, NO2, CN, OR13, NR13R14, NHCOR13, CF3, COR13, R13, CONR13R15, S02NR13RM, SO2R13, NR13SO2R14, OCH2CH2OH, OCH2CH2OMe, morpholine, piperidine, and piperazine; each R11 is independently halogen, N02, CN, OR13, NR13R14, NHCOR13, CF3, COR13, R13, CONR13R14, S02NR13R14, SO2R13, OR13, NR13S02R14, OCH2CH2OH, OCH2CH2OMe, morpholine, piperidine or piperazine; each R12 is independently a hydrocarbyl group optionally containing one or more heteroatoms and optionally substituted with one or more R11 groups; each R13 and each R14 is independently H or an alkyl group; and R15 is an alkyl group; providing that when - Z is CR10 and R9 is H, at least one of R7, R8 and R9 is other than OMe; and - Z is CR10 and R7'9 are all H, R10 is other than OCF2CHF2. In one preferred embodiment of the invention, one of R1 and R2 is selected from (CH2)mRn, (CH2)mR12, (CH2)mNR12R13, (CH2)mNR13COR12, and (CH2)mOR12. In one preferred embodiment of the invention, R1 is selected from (CH2)mRn, (CH2)mR12, (CH2)mNR12R13, (CH2)mNR13COR12, and (CH2)mOR12. hi one preferred embodiment, one of R1 and R2 is selected from N02, CN, halogen, CH2Rn, CH2R12, OR12, NR12R13, NR13COR12, CH2NR12R13, CH2NHSO2R14, CF3, NR13R14, R13, CH2NR13COR12 and NR13SO2R12. In another preferred embodiment, R1 is selected from NO2, CN, halogen, CH2RU, CH2R12, OR12, NR12R13, NR13COR12, CH2NR12R13, CH2NHSO2R14, CF3, NRI3R14, R13, CH2NR13COR12 andNR13SO2R12. In one particularly preferred embodiment of the invention, R1 is selected from N02, CN, halogen, (CH,)^11, (CH2)mR12, (CH2)mNR12R13, (CH2)mNR13COR12, and (CH2)mOR12. hi another preferred embodiment, R1 is selected from NO2, CN, halogen, CH2R11, CH2R12, OR12, NR12R13, NR13COR12, CH2NR12R13 and CH2NHS02R14. In one preferred embodiment, R4 is H, OR13, halogen or R13. hi a more preferred embodiment, R4 is H, OMe, Me or F. In one particularly preferred embodiment, each R12 is independently selected from alkyl, alkenyl, alkynyl, aralkyl, a cyclic group, a saturated or unsaturated alicyclic group, and an aryl group, each of which may optionally contain one to four heteroatoms selected from 0, S, and N, and each of which may optionally be substituted with one, two or three R11 groups. In one particularly preferred embodiment, each R12 is independently selected from alkyl, alkenyl, alkynyl, aralkyl, a heteroaryl group, a saturated or unsaturated alicyclic group optionally contain one to four heteroatoms selected from O, S, and N, and an aryl group, each of which may optionally be substituted with one, two or three R11 groups. In one preferred embodiment, R12 is selected from aryl, aralkyl heteroaryl and a saturated alicyclic group optionally contain one to four heteroatoms selected from O, S, and N, each of which may optionally be substituted with one, two or three R11 groups. In a more preferred embodiment, R12 is selected from phenyl, benzyl, 1,2,4-triazolyl, Npiperidinyl, N-morpholino, N-pyrrolidinyl and N-piperidinyl, each of which may optionally be substituted with one, two or three Ru groups. In an even more preferred embodiment, R12 is selected from phenyl, benzyl, 1,2,4-triazolyl, N-piperidinyl, N-morpholino, N-pyrrolidinyl and N-piperidinyl, each of which may optionally be substituted with one, two or three substituents selected from NO2, CONR13R14, (CH2)qOR13 andR13. In a further preferred embodiment, R12 is selected from phenyl, benzyl, 1,2,4-triazolyl, Npiperidinyl, N-morpholino, N-pyrrolidinyl and N-piperidinyl, each of which may optionally be substituted with one, two or three substituents selected from NC2, CONH2, CH2CH2OH, CH2OH and Me groups. Preferably, R15 is a Ci.s alkyl group. Preferably, each R13 and each R14 is independently H or a C alkyl group. Even more preferably, each R13 and R14 is independently H or an unsubstituted C alkyl group. In one especially preferred embodiment of the invention, each R12 is independently selected from alkyl, alkenyl, alkynyl, aralkyl, a cyclic group, a saturated or unsaturated alicyclic group, and an aryl group, each of which may optionally contain one to four heteroatoms selected from O, S, and N, and each of which may optionally be substituted with one, two or three R1l groups; each R13 and each R14 is independently H or a C\.s alkyl group; and R15 is a CM alkyl group. Preferably, R15 is an unsubstituted CM alkyl group. In one preferred embodiment, each R11 is independently halogen, NO2, CN, (CH2)qOR13, (CH2)rNR13R14, NHCOR13, CF3, COR13, R13, CONRBR14, SO2NR13RU, SO2R13, NR13S02RW, OCH2CH2OH, OCH2CH2OMe, NR13SO2R12, (CH2)SNR12R13, morpholino, piperidinyl or piperazinyl, where q, r and s are each independently 0,1,2,3 or 4. In another preferred embodiment, each Rn is selected from halogen, NO2, CN, OH, NH2} NHCOMe, CF3, COMe, Me, Et, 'Pr, NHMe, NMea, CONH2, CONHMe, CONMe2, S02NH2, SO2NHMe, SCfeNMe^ SO2Me, OMe, OEt, OCH2CH2OH, OCH2CH2OMe, morpholino, piperidinyl and piperazinyl. 11 ' In another especially preferred embodiment, R is selected from halogen, NO2, CN, OH, NH2, NHCOMe, CF3, COMe, Me, Et, jPr, NHMe, NMe2, CONH2, CONHMe, CONMe2, * SO2NH2, SO2NHMe, SO2NMe2, SO2Me, OMe, OEt, OCH2CH2OH, OCH2CH2OMe, morpholino, piperidinyl and piperazinyl. In a preferred embodiment, one of R1 and R2 is selected from NO2, NH2, N(Et)COMe, NHCOMe, N(Me)COMe, NCPr)COMe, NHMe, Cl, F, CN, CH2NHSO2Me, OMe, CH2NCPr)(Et), NHEt, CH2NHCH2Ph, NHEt, Me, CH2NMe2, OH, CF3, NMeSO2Me, GH2NCPr)COMe, CH2OH, CH2NEt2 (Figure Removed) In a more preferred embodiment, R1 is selected from NO2, NH2, N(Et)COMe, NHCOMe, N(Me)COMe, NCPr)COMe, NHMe, Cl, F, CN, CH2NHS02Me, OMe, CH^PrXEt), NHEt, CH2NHCH2Ph, NHEt, Me, CH2NMe2, OH, CF3, NMeSO2Me, CH2NCPr)COMe, CH2OH, CH2NEt2 (Figure Removed) In one preferred embodiment, R2is H, halogen, OR13 or (CH2)mR12. Even more preferably, R2 is selected from H, Cl, OMe, OEt (Figure Removed) In one particularly preferred embodiment, R1 is selected from N02, NH2, N(Et)COMe, NHCOMe, N(Me)COMe, N(!Pr)COMe, NHMe, Cl, F, CN, CH2NHSO2Me, OMe, , NHEt, CH2NHCH2Ph, (Figure Removed) In one preferred embodiment, R7, R8, R9, and R10 are each independently selected from H, halogen, N02, CN, OH, NH2, NHCOMe, CF3, COMe, Me, Et, ;Pr, NHMe, NMe2, CONHMe, CONMe2, SO2NH2, SO2NHMe, SO2NMe2, SO2Me, OMe, OEt, OCH2CH2OH, OCH2CH2OMe, CH2OH, morphoUno, piperidinyl, and pipera2myl. In one preferred embodiment, R6 and R9 are both H. In one preferred embodiment, R7 is selected from H, NO2, NR13R14, OR13, CN, CF3, CH2OR13, S02R13 and halogen. In a more preferred embodiment, R7 is selected from H, NO2, NH2, OH, OMe, CN, CH2OH, F, CF3 and S02Me. In one preferred embodiment, R8 is selected from H, OR13, NO2, OCH2CH2OMe, halogen, NR13R14, N-morpholino and OR13. In a more preferred embodiment, R8 is selected from H, OH, N02, OCH2CH2OMe, Cl, F, NMe2, N-morpholino, Me and OMe. In another particularly preferred embodiment, R7, R8, R9, and R10 are each independently selected from H, halogen, N02, CN, OH, NH2, NHCOMe, CF3, COMe, Me, Et, !Pr, NHMe, NMe2, CONHMe, CONMe2, SO2NH2, SO2NHMe, SO2NMe2, SCbMe, OMe, OEt, OCH2CH2OH, OCH2CH2OMe, morpholino, piperidinyl, and piperazinyl. Preferably, R7, R8 and R9 are each independently selected from H, halogen, NO2, CN, OR13, NR13R14, NHCOR13, CF3, COR13, R13, CONR13R14, SO2NR13R14, S02R13, OR13, NR13SO2R14, OCH2CH2OH, OCH2CH2OMe, morpholino, piperidinyl and piperazinyl. Preferably, R2 is H or halogen; R4 is H or OR13; R6 and R9 are both H; R7 is selected from H, NO2, NR13R14, OR13 and CN; R8 is selected from H, OR13, NO2, OCH2CH2OMe, halogen, NR13R14, N-morphohno and OMe. Preferably, where Z is CR10 and R9 is H, at least two of R7, R8 and R10 are other than OMe. In yet another particularly preferred embodiment, R2isHbrCl; R4 is H or OMe; R7 is selected from H, NO2, NH2, OH, OMe and CN; and R8 is selected from H, OH, N02, OCH2CH2OMe, Cl, F, NMe2, N-morpholino. In one preferred embodiment, Z is CR10. Preferably, R10 is selected from H, halogen, NO2) CN, OR13, NR13R14, NHCOR13, CF3, COR13, R13, CONR13R14, S02NR13R14, SO2R13, NR13S02R14, OCH2CH2OH, OCH2CH2OMe, morpholino, piperidinyl and piperazinyl. More preferably, R10 is selected from N02, NH2, H, OH, OMe, CN, F, CH2OH, CF2 and S02Me. More preferably still, R10 is H. In another preferred embodiment, Z is N. Another aspect of the invention relates to a compound selected from the following: 4-[4-(3-Nitro-phenyl)-pyriraidin-2-ylamino]-phenol [1]; (4-Nitro-phenyl)-[4-(3-nitro-phenyl)-pyrmiidin-2-yl]-amine[2]; [4-(3-Ainino-phenyl)-pyrirnidin-2-yl]-[4-(2-methoxy-ethoxy)-phenyl]-amine[3]; [4-(3-Amino-phenyl)-pyrmiidm-2-yl]-(4-nirro-phenyl)-anime [4]; (3-Nitro-phenyl)-[4-(3-nitro-phenyl)-pyrirnidm-2-yl]-amine [5]; (4-Fluoro-phenyl)-[4-(3-nitro-phenyl)-pyrimidin-2-yl]-amine[6]; [4-(3-Arnino-phenyl)-pyriinidni-2-yl]-(4-fluoro-phenyl)-amine[7]; N-[4-(3-Ammo-phenyl)-pyrimidin-2-yl]-benzene-l,3-diamine[8]; N,N-Dimethyl-N1-[4-(3-nitro-phenyl)-pyrimidui-2-yl]-benzene-l,4-diamine[9J; N-Emyl-N-{3-[2-(4-hydroxy-phenylammo)-pyrirrudm^yl]-phenyl}-acetamide[10]; N-{3-[2 N- {3-[2-{4-Hydroxy-phenylamino)-pyrimidin-4-yl]-phenyl} -N-methyl-acetamide [12]; N-{3-[2-(4-Hydroxy-phenylanimo)-pyriniidin-4-yl]-phenyl}-N-isobutyl-acetamide[13]; 4-[4-(3-Methylammo-phenyl)-pyrimioMn-2-ylamino]-phenol [14]; 4-[4-(3-Armno-phenyi)-pyrirnidin-2-ylarnino]-phenol[15]; (4-CMoro-phenyl)-[4-(3-cUoro-phenyl)-pyrirnidin-2-yl] -amine [16]; 4-[4-(3-Chloro-phenyl)-pyrimidin-2-ylamino]-phenol [17]; 3-[4-(3-CMoro-phenyl)-pyrimidin-2-ylamino]-phenol [18] 14 [4-(3-Amino-phenyl)-pyrimidin-2-yl]-(3-nitro-phenyl)-amine[19]; N-[4-(3,4-Dichloro-phenyl)-pyrimidin-2-yl]-N',N'-dimethyl-benzene-1,4-diamine [20]; 4-[4-(3,4-Dichloro-phenyl)-pyrimidin-2-ylamino]-phenol[21]; 3-[4-(3)4-Dichloro-phenyl)-pyrimidin-2-ylamino]-phenol[22]; N-Ethyl-N-{3-[2-(4-methoxy-phenylamino)-pyrtmidin-4-yl]-phenyl}-acetamide[23]; N-Ethyl-N- {3-[2-(4-nitro-phenylamino)-pyrimidin-4-yl]-phenyl} -acetamide [24]; [4-(3-Ethylamino-phenyl)-pyrimidin-2-yl]-(4-methoxy-phenyl)-amine [25]; [4-(3-Ethylamino-phenyl)-pyrimidin-2-yl]-(4-nitro-phenyl)-amine [26]; {4-[3-(Benzylamino-methyl)-phenyl]-pyrimidin-2-yl}-(3-nitro-phenyl)-amine[27]; 3-{4-[3-(Benzylaniino-me1hyl)-phenyl]-pyrimidin-2-ylamino}-phenol[28]; [4-(3-Imidazol-l-ylmethyl-phenyl)-pyrinudin-2-yl]-(3-nitro-phenyl)-amine[29]; (3-Nitro-phenyl)-[4 [4-(3,4-Dichloro-phenyl)-pyrimidin-2-yl]-(3-nitro-phenyl)-aniine[31]; (4-MorphoUn-4-yl-phenyl)-[4-(3-[l,2,4]triazol-l-ylmethyl-phenyl)-pyrimidin-2-yl]-amiiie [32]; 4-[4-(3-[l,2,4]Triazol-l-ylmetiiyl-phenyl)-pyrimidin-2-ylamino]-phenol[33]; 3-[4-(3-[l32,4]Triazol-l-ylmethyl-phenyl)-pyriiiiidin-2-ylamino]-phenol[34]; (3-Metiioxy-phenyl)-[4-(3-[l,2)4]triazol-l-ylmethyl-phenyl)-pyrimidin-2-yl]-amine[35]; 3-[4-(3-[ 1,2,4]Triazol-1 -ylmethyl-phenyl)-pyrimidin-2-ylainino]-benzonitrile [3 6] Phenyl-(4-phenyl-pyrimidin-2-yl)-amine[37]; [4-(5-Fluoro-2-methoxy-phenyl)-pyrimidin-2-yl]-phenyl-amine[38]; [4-(3-Morpholin-4-ylmethyl-phenyl)-pyrimidin-2-yl]-(3-m1ro-phenyl)-arnine[39]; N- {3-[2-(3-Nitro-phenylamino)-pyrimidin-4-yl] -benzyl} -methanesulfonamide [40]; (4-Nitro-phenyl)-[4-(3-[ 1,2,4]triazol-1 -ylmethyl-phenyl)-pyriinidm-2-yl]-amine [41 ]; (4-Methoxy-phenyl)-[4-(3-[ 1,2,4]triazol-l -ylmethyl-phenyl)-pyrimidin-2-yl] -amine [42]; N,N-Dimethyl-N'-[4-(3-[ 1,2,4]triazol-l -ylmethyl-phenyl)-pyrinlidin-2-yl]-benzene-1,4- diamine [43]; [4-(2,5-Dimethoxy-phenyl)-pyrimidin-2-yl] -(3-nitro-phenyl)-amine [44]; 4-[4-(2,5-Dimethoxy-phenyl)-pyrimidin-2-ylamino]-phenol[45]; (4-{3-[(Etiiyl-isopropyl-amino)-methyl]-phenyl}-pyrimidin-2-yl)-(3-nitro-phenyl)-ainine [46]; [4-(4-ailoro-3-[l,2,4]triazol4-ylmethyl-phenyl)-pyriniidin-2-yl]-(3-nitro-phenyl)-amine [47]; {4-[3-(Ben2ylamino-methyl)-phenyl]-pyriinidin-2-yl}-(6-chloro-pyridin-3-yl)-ainine [48]; [4-(3,4-Dichloro-phenyl)-pyrimidin-2-yl]-(6-methoxy-pyridin-3-yl)-amine[49]; (6-Methoxy-pyridin-3-yl)-[4-(3-[l,2,4]triazol-l-ylmethyl-phenyl)-pyriniidib-2-y^ [50]; . 3-[2-(6-Methoxy-pyridin-3-ylamino)-pyrimidin-4-yl]-benzonitrile [51]; [4-(2,5-Dimethoxy-phenyl)-pyrimidin-2-yl]-(6-methoxy-pyridin-3-yl)-amine[52]; (4-{3-[(EthyI-isopropyl-amino)-methyl]-phenyl}-pyrimidin-2-yl)-(6-methoxy-pyridin-3- yl)-amine [53]; {4-[3-(4-Methyl-piperazin-l-yImethyl)-phenyl]-pyrimidin-2-yl}-(3-nitro-phenyl)-amine [54]; 3-[2-(3-Nitro-phenylamino)-pyriniidin-4-yl]-phenol[55]; [3-[2-(3-Hydroxy-phenylamino)-pyrimidin-4-yl]-phenol [56]; 3-[2-(3-Fluoro-phenylamino)-pyrimidin-4-yl]-plienol [57]; (6-Methoxy-pyridin-3-yl)- (4-[3-(4-methyl-piperazin-1 -ylmethyl)-phenyl]-pyrimidin-2- yl}-amine [58]; [4-(3-Irmdazol-l-y]methyl-phenyl)-pyrimidm^^ N-{3-[2-(3-Hydroxymethyl-phenylamino)-pyrimidin-4-yl]-phenyl}-acetamide[60]; [4-(2,5-Dimethyl-phenyl)-pyrimidin-2-yl]-(3-nitro-phenyl)-ajnine[61]; 3-[4-(2,5-Dimethyl-phenyl)-pyrimidin-2-ylamino]-phenol[62]; [4-(2,5-Dimethyl-phenyl)-pyrimidin-2-yl]-(3-fluoro-phenyl)-amine[63]; 3-[4-(3-Nitro-phenyl)-pyrimidin-2-ylamino]-phenol [64]; (3-Fluoro-phenyl)-[4-(3-nitro-phenyl)-pyrimidin-2-yl]-amine[65]; N-[3-(2-Phenylamino-pyrimidin-4-yl)-phenyl]-acetamide[66]; N- {3-[2-(3-Hydroxy-phenylamino)-pyrimidin-4-yl]-phenyl} -acetamide [67]; N- {3-[2-(3,5-Dimethoxy-phenylamino)-pyrimidin-4-yl]-phenyl} -acetamide [68]; N- {3-[2-(3-Nitro-phenylamino)-pyrimidin-4-yl]-phenyl} -acetamide [69]; 16 N- {3-[2-(Pyridin-3-ylamino)-pyrimidin-4-yl]-phenyl}-acetamide [70]; [4-(3-Dimethylaininomethyl-phenyl)-pyrimidin-2-yl]-(3-iiitro-phenyl)-ainine[71]; 3 -[2-(3-Hydroxymethyl-phenylamino)-pyrimidin-4-yl]-phenol [72]; 3 -[2-(Pyridin-3-ylamino)-pyrimidin-4-yl]-phenol [73]; 3-[2-(6-Methoxy-pyridin-3-ylamino)-pyrimidin-4-yl]-phenol [74]; 3-[2-(3,5 -Bis-trifluoromethyl-phenylamino)-pyrimidin-4-yl]-phenol [75]; 3-[4-(4-Methoxy-phenyl)-pyriinidin-2-ylairiino]-phenol[76]; [4-(3-Methoxy-phenyl)-pyrimidin-2-yl] N-Isopropyl-N-{3-[2-(3-mtro-phenylanuno)-pyrimidin-4-yl]-ben2yl}-acetamide[78]; (l-{3-[2-(3-Nitro-phenylamino)-pyrimidin-4-yl]-benzyl}-piperidin-2-yl)-inethanol [79]; 3-[4-(3-Dimethylaminomethyl-phenyl)-pyriinidin-2-ylamino]-phenol [80]; 4-[4-(3-Dimethylaminome1hyl-phenyl)-pyTiinidin-2-ylamino]-phenol[81]; [4-(34}imethylaminomethyl-phenyl)-pyr^ [82]; [4-(3-Dimethylaminomethyl-phenyl)-pyrimidin-2-yl]-(6-melhoxy-pyridin-3-yl)-amin [83]; [4-(3-Diethylaminomethyl-phenyl)-pyrimidin-2-yl]-(3-intro-phenyl)-aniine[84]; N-Methyl-3-nitro-N- {3-[2-(3-nitro-phenylaraino)-pyrimidin-4-yl]-benzyl} - benzenesulfonamide [85]; (3-Nitro-phenyl)-{4-[3 2-yl}-amine [86]; [4-(3-Methoxy-phenyl)-pyrimidin-2-yl]-(3-nitro-phenyl)-amine[87]; 3-[4-(3-Methoxy-phenyl)-pyrimidin-2-ylamino]-phenol[88]; 4-[4-(3,4-Dimethoxy-phenyl)-pyrimidin-2-ylamino]-phenol [89]; [4-(3,4-Dimethoxy-phenyl)-pyrimidin-2-yl]-(3-nitro-phenyl)-amine[90]; {3-[2 3-[2-(3-Hydroxy-phenylamino)-pyrimidin-4-yl]-benzonitrile[92]; 3-[2-(4-Hydroxy-phenylamino)-pyrimidin-4-yl]-benzonitrile[93]; [4-(4-Methoxy-phenyl)-pyrimidin-2-yl]-(3-nitro-phenyl)-amine[94]; 3-[4-(3-Trifluoromethyl-phenyl)-pyrimidin-2-ylamino]-phenol[95]; 4-[4-(3-Trifluoromethyl-plienyl)-pytimidin-2-ylamino]-phenol[96]; (3-Nitro-phenyl)-[4-(3-trifluoromethyl-phenyl)-pyrimidin-2-ylJ-amine[97]; 4-[4-(3-Methoxy-phenyl)-pyrimidin-2-ylamino]-phenol[98]; 1- {3-[2-(3-Nitro-phenylamino)-pyrimidin-4-yl]-benzyl} -piperidine-3-carboxylic acid amide [99]; 2-(l-{3-[2-(3-Nitro-phenylamino)-pyrimidin-4-yl]-benzyl}-piperidin-3-yl)-ethariol[100]; (1 - {3-[2-(4-Moipholin-4-yl-phenylamino)-pyrimidin-4-yl]-benzyl} -piperidin-2-yl)- methanol[101]; (l-{3-[2-(6-Methoxy-pyridin-3-ylamino)-pyriniidin-4-yl]-benzyl}-piperidm-2-yl)- methanol[102]; 3- {4-[3-(2-Hydroxymethyl-piperidin-1 -ylmethyl)-phenyl]-pyriinidin-2-ylamiiio} -phenol [103]; (3-Methanesulfonyl-phenyl)-[4-(3-[l,2,4]triazol-l-ylmethyl-phenyl)-pyrimidin-2-yl]- amine [104]; (l-{3-[2-(3-Nitro-phenylamino)-pyriinidin-4-yl]-benzyl}-piperidin-3-yl)-methanol[105 4-{4-[3-(2-Hydroxymethyl-piperidin-l-ylmethyl)-phenyl]-pyrimidin-2-ylaraino}-phenol [106]; (l-{3-[2-(3,5-Bis-hydroxymethyl-phenylamino)-pyrimidin-4-yl]-benzyl}-piperidiQ-2-yl)- methanol [107]; (l-{3-[2-(4-Methyl-3-iiitro-phenylaniino)-pyrimidin-4-yl]-benzyl}-piperidin-2-yl)- methanol [108]; 3.[4-(4-Ethoxy-phenyl)-pyrimidin-2-ylamino]-phenol [ 109]; 4-[4-(4-Methoxy-phenyl)-pyrimidin-2-ylamino]-phenol [110]; [4-(4-Methoxy-phenyl)-pyrimidin-2-yl]-(4-morpholin-4-yl-phenyl)-amine [111]; [4-(3-Chloro-phenyl)-pyrimidin-2-yl]-(3-nitro-phenyl)-amine [112]; 4-[4-(3-Fluoro-phenyl)-pyrimidin-2-ylamino]-phenol [113]; 3-[4-(2,5-Difluoro-phenyl)-pyriinidin-2-ylamino]-phenol [114]; 3-[4-(3-Hydroxymethyl-phenyl)-pyrimidin-2-ylamino]-phenol [115]; {3-[2-(3-Fluoro-phenylamino)-pyrimidin-4-yl]-phenyl}-methanol [116]; {3-[2-(3,5-Dinitro-phenylammo)-pyrimidin-4-yl]-phenyl}-methanol [117]; (3-Fluoro-phenyl)-[4-(3-methoxy-phenyl)-pyrimidm-2-yl]-amine [118]; (3-Fluoro-phenyl)-[4-(4-methoxy-phenyl)-pyrimidin-2-yl]-amine [119]; 3-[2-(3,4,5-Trmie1hoxy-phenylamino)-pyrimidin-4-yl]-phenol[120]; 3-[2-(3,5-Dimethoxy-phenylamino)-pyriniidin-4-yl]-phenol[121]; 3-[2-(4-Hydroxy-phenylamino)-pyrimidin-4-yl] -phenol [ 122]; [4-(2,5-Difluoro-phenyl)-pyrimidm-2-yl]-(3-m'tro-phenyl)-amine [ 123]; [4-(4-Methoxy-phenyl)-pyrmudm-2-yl]-(6-memoxy-pyridin-3-yl)-amine[l24]; {3-[2-(6-Methoxy-pyridin-3-ylamino)-pyrinudin-4-yl]-phenyl}-methanol [125]; (3-Nitro-phenyl)- {4-[4-(2-[l ,2,4]triazol-1 -yl-ethyl)-phenyl] -pyrimidin-2-yl} -amine [ 126]; (l-{4-[2-(3-Nitro-phenylamino)-pyriniidin-4-yl]-berizyl}-piperidm-2-yl)-rnethanol[127]; [4-(4-Memoxy-phenyl)-pyrimidin-2-yl]-(3A5-trimemoxy-phenyl)-amine [128]; N-Methyl-N- {3-[2-(3-nitro-phenylamino)-pyrimidin-4-yl] -phenyl} -methanesulfonamide [129]; N- {3-[2-(3-Hydroxy-phenylamino)-pyrimidin-4-yl]-phenyl} -N-methylmethanesulfonamide [130]; N-{3-[2-(4-Hydroxy-phenylarnino)-p>rirriidm-4-yl]-phenyl}-N-methylmethanesulfonamide [131]; and N-{3-[2-(6-Methoxy-pyridm-3-ylarrmio)-pyrirrddin-4-yl]-phenyl}-N-methylmethanesulfonamide [132]. In one embodiment, the present invention relates to a compound selected from the following: 4-[4-(3-Nitro-phenyl)-pyrimidin-2-ylamino]-phenol[l]; (4-Nitro-pheaiyl)-[4-(3-mtro-phenyl)-pyrimidin-2-yl]-amine[2]; [4-(3-Ammo-phenyl)-pyrimidui-2-yl]-[4-(2-memoxy-ethoxy)-phenyl]-amine[3]; [4-(3-Amino-phenyl)-pyrimidin-2-yl]-(4-nitro-phenyl)-arnine[4]; (3-Nitro-phenyl)-[4-(3-mtro-phenyl)-pyrimidin-2-yl]-amine[5]; (4-Fluoro-phenyl)-[4-(3 -nitro-phenyl)-pyrimidin-2-yl]-arnine [6]; [4-(3-Amino-phenyl)-pyrirnidin-2-yl]-(4-fluoro-phenyl)-amine[7]; N-[4-(3-Amino-phenyl)-pyrimidin-2-yl]-benzene-1,3-diamine [8]; N,N-Dimethyl-N'-[4-(3-nitro-plienyl)-pyrimidm-2-yl]-benzene-l,4-diamine[9]; N-Ethyl-N-{3-[2-(4-hydroxy-phenylamino)-pyrimidin-4-yl]-phenyl}-acetamide [10]; N-{3-[2-(4-Hydroxy-phenylamino)-pyrimidin-4-yl]-phenyl}-acetamide [11]; N-{3-[2-(4-Hydroxy-phenylamino)-pyrimidin-4-yl]-phenyl}-N-methyl-acetamide[12]; N-{3-[2-(4-Hydroxy-phenylamino)-pyrimidin-4-yl]-phenyl}-N-isobutyl-acetamide[13]; 4-[4-(3-Methylamino-phenyl)-pyrimidin-2-ylamino]-phenol[14]; 4-[4-(3-Amino-phenyl)-pyrimidin-2-ylamino]-phenol[15]; (4-CWoro-phenyl)-[4-(3-cWoro-phenyl)-pyrimidin-2-yl]-amine[16]; 4-[4-(3-Chloro-phenyl)-pyrimidin-2-ylamino]-phenol [17]; 3-[4-(3-Chloro-phenyl)-pyrimidin-2-ylamino]-phenol [18]; [4-(3-Amino-phenyl)-pyrimidin-2-yl]-(3-nitro-phenyl)-amine [19]; N-[4-(3,4-Dichloro-phenyl)-pyriimdin-2-^^^ 4-[4-(3,4-Dichloro-phenyl)-pyrimidin-2-ylamino]-phenol [21]; 3-[4-(3,4-Dichloro-phenyl)-pyrimidin-2-ylamino]-phenol[22]; N-Ethyl-N-{3-[2-(4-methoxy-phenylamino)-pyrimidin-4-yl]-phenyl}-acetamide[23]; N-Ethyl-N-{3-[2-(4-nitro-phenylamino)-pyrimidin-4-yl]-phenyl}-acetamide[24]; [4-(3-Ethylammo-phenyl)-pyrimidin-2-yl]-(4-methoxy-phenyl)-amine[25]; [4-(3-Ethylamino-phenyl)-pyriinidin-2-yl]-(4-nitro-phenyl)-amine [26]; {4-[3-(Benzylamino-methyl)-phenyl]-pyrimidin-2-yl}-(3-nitro-phenyl)-amine[27]; 3- {4-[3-(Benzylamino-methyl)-phenyl]-pyrimidin-2-ylainino}-phenol [28]; [4-(3-Imidazol-l-ylmethyl-phenyl)-pyrimidin-2-yl]-(3-nitro-phenyl)-amine[29]; (3-Nitro-phenyl)-[4-(3-[l,2,4]triazol-l-ylmethyl-phenyl)-pyrimidin-2-yl]-amine[30]; [4-(3,4-Dichloro-phenyl)-pyrimidin-2-yl]-(3-nitro-phenyl)-amine [31]; (4-Morpholin-4-yl-phenyl)-[4-(3-[ 1,2,4]triazol-1 -ylmethyl-phenyl)-pyrimidin-2-yl]-amine [32]; 4-[4-(3-[l ,2,4]Triazol-1 -ylmethyl-phenyl)-pyrimidin-2-ylainino]-phenol [33]; 3-[4-(3-[l,2,4]Triazol-l-ylmethyl-phenyl)-pyrimidin-2-ylamino]-phenol[34]; (3-Methoxy-phenyl)-[4-(3-[l,2,4]MazoI-l-ylmethyl-phenyl)-pyrimidin-2-yl]-amine[35]; 3-[4-(3-[lA4]Triazol-l-ylmethyl-phenyl)-pyrimidiri-2-ylaniino]-benzonitrile[36]; Phenyl-(4-phenyl-pyrimidin-2-yl)-amine[37]; [4-(5-Fluoro-2-methoxy-phenyl)-pyriniidin-2-yl]-phenyl-amine [38]; [4-(3-Morpholin-4-ylmemyl-phenyl)-pyrimidm-2-yl]-(3-nitro-phenyl)-amine[39]; N-{3-[2-(3-Nitro-phenylammo)-pyrimidin-4-yl]-benzyl}-methanesulfonamide[40]; (4-Nitro-phenyl)-[4-(3-[l,2,4]1riazol-l-ymiethyl-phenyl)-pyrimidm-2-yl]-amme[4l]; (4-Methoxy-phenyl)-[4-(3-[ 1,2,4]triazol- l-yhnethyl-phenyl)-pyrimidin-2-yl]-amine [42]; N,N-Dimethyl-N'-[4-(3-[l,2J4]triazol-l-yhiiethyl-phenyl)-pyriniidin-2-yl]-benzene-l,4- diamine [43]; [4-(2,5-Dimethoxy-phenyl)-pyrimidin-2-yl]-(3-nitro-phenyl)-amine[44]; 4-[4-(2,5-Dimemoxy-phenyl)-pyrimidin-2-ylamino]-phenol [45]; (4-{3-[(Emyl-isopropyl-animo)-memyl]-phenyl}-pyrhTaidin-2-yl)-(3-mtro-phenyl)-arn [46]; [4-(4-CMoro-3-[ 1,2,4]triazol-1-ylmernyl-phenyl)-^ [47]; (4-[3-(Benzylaniino-memyl)-phenyl]-pyrimidm-2-yl}-(6-cUoro-pyridm-3-yl)-amine [48]; [4-(3,4-DicUoro-phenyl)-pyrimidin-2-yl]-(6-methoxy-pyridin-3-yl)-arnine [49]; (6-Memoxy-pyridin-3-yl)-[4-(3-[l,2,4]triazol-l-yrniemyl^ [50]; 3-[2-(6-Methoxy-pyridin-3-ylamino)-pyrirnidin-4-yl]-benzonirrile [51]; [4-(2,5-Dimethoxy-phenyl)-pyrimidm-2-yl]-(6-methoxy-pyridm-3-yl)-arnine [52]; and (4-{3-[(Emyl-isopropyl-ammo)-memyl]-phenyl}-pyrirrddm-2-yl)-(6-methoxy-pyridin yl)-amine [53]. In another particularly preferred embodiment of the invention, the compound is selected . from [3], [10], [11], [26], [29], [30], [34], [39], [40], [44], [46], [53], [54], [58], [78], [79L [80], [81], [82], [83], [99], [100] and [103]. 5 • In another particularly preferred embodiment of the invention, the compound is selected from [3], [26], [29], [40], [44], [46], [53], [54], [78], [79], [80], [81], [83], [99] and [100]. In another particularly preferred embodiment of the invention, the compound is selected from [26], [44], [46], [54], [79], [83] and [100]. In another particularly preferred embodiment of the invention, the compound is selected from [46], [79] and [100]. In one preferred embodiment, the compound of the invention is capable of inhibiting one or more protein kinases selected from CDKl/cyclin B, CDK2/cyclin A, CDK2/cyclin E, CDK4/cyclin Dl, CDK7/cyclin H, CDK9/cyclin Tl, GSK30, aurora kinase and PLK1, as measured by the appropriate assay. In one particularly preferred embodiment, the compound of the invention exhibits an ICso value for kinase inhibition of less than 10 uM, more preferably less than 1 jjM, more preferably still less than 0.1 fjM. Compounds falling within each of these preferred embodiments can be identified from Table 1, which shows the ICso values for compounds [1]-[134]. Details of the various kinase assays are disclosed in the accompanying Examples section. In one preferred embodiment, the invention relates to compounds that are capable of exhibiting an antiproliferative effect against one or more transformed human cell lines in vitro as measured by a 72-h MTT cytotoxicity assay. In a particularly preferred embodiment, the compound of the invention exhibits an ICso value (average) of less than 10 ^M against one or more transformed human cell lines in vitro as measured by a 72-h MTT cytotoxicity assay. More preferably, the compound exhibits an ICso value (average) of less than 5 pM, more preferably still, less than 1 uM. Compounds falling within each of these preferred embodiments can be identified from Table 2, which shows the ICso values for selected compounds of the invention. Details of the various cytotoxicity assays are disclosed in the accompanying ^Examples section. In a preferred embodiment, the invention relates to compounds that are capable of exhibiting an antiproliferative effect against one or more transformed human cell lines in vitro, wherein said compound is selected from the following: [4-(3-Ammo-phenyl)-pyrimidin-2-yl]-[4-(2-methoxy-ethoxy)-phenyl]-amine[3]; N-Ethyl-N- {3-[2-(4-hydroxy-phenylamino)-pyriniidin-4-yl]-phenyl} -acetamide [10]; N-{3-[2-(4-Hydroxy-phenylainino)-pyrimidin-4-yl]-phenyl}-acetamide [11]; 3-{4-[3-(Benzylamino-methyl)-phenyl]-pyrimidin-2-ylainino}-phenol [28]; [4-(3 -Lnidazol-1 -ylmethyl-phenyl)-pyrimidin-2-yl] -(3-nitro-phenyl)-amine [29]; (3-Nitro-phenyl)-[4-(3-[ 1,2,4]triazol-1 -ylmethyl-phenyl)-pyrimidin-2-yl] -amine [30]; (4-Moipholin-4-yl-phenyl)-[4-(3-[l,2,4]triazol-l-ylmetiiyl-phenyl)-pyrimidin-2-yl]-amine [32]; 4-[4-(3-[l,2,4]Triazol-l-ylmetliyl-phenyl)-pyrimidin-2-ylamino]-phenol [33]; 3-[4-(3-[l,2,4]Triazol-l-ylmethyl-phenyl)-pyrimidin-2-ylamino]-phenol[34]; (3-Metiioxy-phenyl)-[4-(3-[l,2,4]triazol-l-ylmethyl-phenyl)-pyrimidin-2-yl]-arnme [35]; and (6-Methoxy-pyridm-3-yl)-[4-(3-[l,2,4]triazol-l-^ [50]. Even more preferably, the compound of the invention is capable of exhibiting an ICso value (average) of less than 10 |iM against one or more transformed human cell lines in vitro as measured by a 72-h MTT cytotoxicity assay. Preferably, the compound is selected from the following: [4-(3-Amino-phenyl)-pyriniidin-2-yl]-[4-(2-methoxy-ethoxy)-phenyl]-arnine[3]; N-Emyl-N-{3-[2-(4-hydroxy-phenylammo)-pyrirnidin-4-yl]-phenyl}-acetamide[10]; N- {3-[2-(4-Hydroxy-phenylarnmo)-pyrirnidin-4-yl]-phenyl}-acetamide [11]; [4-(3-Imidazol-l -ymietiiyl-phenyl)-pyrimidin-2-yl]-(3-nitro-phenyl)-amine [29]; (3-Nitro-phenyl)-[4-(3-[l,2,4]triazol-l-yknethyl-phenyl)-pyrimidin-2-yl]-amine[30]; and 3-[4-(3-[l,2,4]Triazol-l-ymiethyl-phenyl)-pyrimioUn-2-ylamino]-phenol[34]. Even more preferably still, the compound of the invention is capable of exhibiting an IC5o value (average) of less than 5 jjM against one or more transformed human cell lines in vitro as measured by a 72-h MTT cytotoxicity assay. Preferably, the compound is selected from: [4-(3-Amino-phenyl)-pyrirnidin-2-yl]-[4-(2-rnethoxy-ethoxy)-phenyl]-amine [3]; and [4-(3-Mda2ol-l-ylmethyl-phenyl)-pyriniidin-2-yl]-(3-nitro-phenyl)-ainine[29]. In another preferred embodiment, the compound of the invention is capable of inhibiting one or more protein kinases selected from CDKl/cyclin B, CDK2/cyclin A, CDK2/cyclin E, CDK4/cyclin Dl, CDK7/cyclin H, CDK9/cyclin Tl, GSK30, aurora kinase and PLK1, as measured by the appropriate assay. Preferablt, the compound is selected from the following: 4-[4-(3-Nitro-phenyl)-pyrimidin-2-ylamino]-phenol[l]; [4-(3-Amino-phenyl)-pyrimidin-2-yl]-[4-(2-methoxy-ethoxy)-phenyl]-amine[3]; N-Ethyl-N-{3-[2-(4-hydroxy-phenylamino)-pyriniidin-4-yl]-phenyl}-acetamide[10]; N-{3-[2-(4-Hydroxy-phenylaniino)-pyrirnidin-4-yl]-phenyl}-acetarnide [11]; N- {3-[2-(4-Hydroxy-phenylamino)-pyrirnidin-4-yl]-phenyl} -N-methyl-acetamide [12]; N- {3- [2-(4-Hydroxy-phenylammo)-pyrimidin-4-yl]-phenyl} -N-isobutyl-acetamide [13]; 4-[4-(3-Methylanmo-phenyl)-pyrirnidui-2-ylamino]-phenol[14]; 4-[4-(3-Ammo-phenyl)-pyrimidm-2-ylamino]-phenol [15]; 4-[4^3-C^loro-phenyl)-pyrimidin-2-ylamino]-phenol [17]; 3-[4-(3-Chloro-phenyl)-pyrimidin-2-ylamino]-phenol [18]; 4-[4-(3,4-Dichloro-phenyl)-pyrimidin-2-ylamino]-phenol[21]; {4-[3-(Benzylamino-methyl)-phenyl]-pyrimidin-2-yl} -(3 -nitro-phenyl)-amine [27]; 3- {4-[3-(Berizylarnmo-memyl)-phenyl]-pyrimidin-2-ylamino}-phenol [28]; [4-(3-JMdazol-l-ylmemyl-phenyl)-pyrimidin-2-yl]-(3-nirro-phenyl)-amine[29]; (3-Nitro-phenyl)-[4-(3-[l,2,4]triazol-l-ylmemyl-phenyl)-pyrmiidm-2-yl]-amine[30]; (4-MorphoHn-4-yl-phenyl)-[4-(3-[l,2,4]triazol-l-yhriethyl-phenyl)-pyrimidin-2-yl]-anTine [32]; 4-[4-(3-[l,2,4]Triazol-l-ymiemyl-phenyl)-pyriim'dm-2-ylamino]-phenol[33]; 3-[4-(3-[l,2,4]Triazol4-ytaiemyl-phenyl)-pyrJrnidin-2-ylarnmo]-phenol[34]; (3-Methoxy-phenyl)-[4-(3-[lJ2,4]triazol-l-ylmethyl-phenyl)-pyrirmdm-2-yl]-amine[3 3-[4-(3-[l,2,4]Triazol-l-ylmethyi-phenyl)-pyrimidin-2-ylamino]-benzonitrile[36]; {4-[3-(Benzylammo-methyl)-phenyl]-pyrirmdm-2-yl}-(6-chloro-pyridm-3-yl)-am^ [48]; and (6-Methoxy-pyridin-3-yl)-[4-(3-[l,2,4]triazol-l-ylmethyl-phenyl)-pyrimidin-2-yl]-aniine [50]. More preferably, the compound exhibits an ICso value (for kinase inhibition) of less than 10 pM. Preferably, the compound is selected from the following: [4-(3-Arru^o-phenyl)-pyrimidin-2-yl]-[4-(2-methoxy-ethoxy)-phenyl]-amine[3]; N-Emyl-N-{3-[2-(4-hydroxy-phenylammo)-pyrimidin-4-yl]-phenyl}-acetamide[10]; N-{3-[2-(4-Hydroxy-phenylamino)-pvrirnidin-4-yl]-phenyl}-acetamide [11]; N- {3-[2-(4-Hydroxy-phenylamino)-pyrimidin-4-yl]-phenyl}-N-methyl-acetamide [12]; 4-[4-(3-Methylammo-phenyl)-pvrimidin-2-ylamino]-phenol [14]; 3-{4-[3-(Benzylammo-methyl)-phenyl]-pyrirnidm-2-ylarnino}-phenol[28]; [4-(3-Imidazol-l-ymiethyl-phenyl)-pyrinMdin-2-yl]-(3-nitro-phenyl)-anune[29]; (3-Nitro-phenyl)-[4-(3-[l,2,4]triazol-l-ylmethyl-phenyl)-pyrimidm-2-yl]-amine [30]; 4-[4-(3-[ 1,2,4]Triazol-1 -yhnemyl-phenyl)-pyrimidin-2-ylarnino]-phenol [33]; 3-[4-(3-[l,2,4]Triazol-l-yhnemyl-phenyl)-pvriniidin-2-ylamino]-phenol[34]; (3-Methoxy-phenyl)-[4-(3-[l,2,4]triazol-l-ymiemyl-phenyl)-pyrimid^-2-yl]-amine[35]; 3-[4-(3-[l,2,4]Triazol-l-ylmethyl-phenyl)-pyrimidm-2-ylammo]-benzonitrile[36];and (6-Memoxy-pyridm-3-yl)-[4-(3-[l,2,4]triazol-l-ymiemyl-phenyl)-pyriniidm-2-yl]- [50]. More preferably still, the compound of said second aspect exhibits an ICso value (for kinase inhibition) of less than 0.1 jjM. Preferably, the compound is selected from the following: [4-(3-Amino-phenyl)-pyrimidin-2-yl]-[4-(2-methoxy-ethoxy)-phenyl]-amine[3]; 4-[4-(3-Methylamino-phenyl)-pyrimidin-2-ylamino]-phenol[14]; (3-Nitro-phenyl)-[4-(3-[l,2,4]triazol-l-ymiemyl-phenyl)-pyriniidin-2-yl]-amine[30];and 3-[4-(3-[l,2,4]Triazol-l-yhnemyl-phenyl)-pvrirnidin-2-ylamino]-benzonitrile [36]. 25 THERAPEUTIC USE The compounds of the present invention have been found to possess anti-proliferative activity and are therefore believed to be of use in the treatment of proliferative disorders such as cancers, leukaemias and other disorders associated with uncontrolled cellular proliferation such as psoriasis and restenosis. As defined herein, an anti-proliferative effect within the scope of the present invention may be demonstrated by the ability to inhibit cell proliferation in an in vitro whole cell assay, for example using any of the cell lines A549, HT29 or Saos-2 Using such assays it may be determined whether a compound is antiproliferative in the context of the present invention. One preferred embodiment of the present invention therefore relates to the use of one or more compounds of the invention in the preparation of a medicament for treating a proliferative disorder. As used herein the phrase "preparation of a medicament" includes the use of a compound of the invention directly as the medicament in addition to its use in a screening programme for further therapeutic agents or in any stage of the manufacture of such a medicament. Preferably, the proliferative disorder is a cancer or leukaemia. The term proliferative disorder is used herein in a broad sense to include any disorder that requires control of the cell cycle, for example cardiovascular disorders such as restenosis, cardiomyopathy and myocardial infarction, auto-immune disorders such as glomerulonephritis and rheumatoid arthritis, dermatological disorders such as psoriasis, anti-inflammatory, anti-fungal, antiparasitic disorders such as malaria, emphysema, alopecia, and chronic obstructive pulmonary disorder. In these disorders, the compounds of the present invention may induce apoptosis or maintain stasis within the desired cells as required. The compounds of the invention may inhibit any of the steps or stages in the cell cycle, for example, formation of the nuclear envelope, exit from the quiescent phase of the cell cycle (GO), Gl progression, chromosome decondensation, nuclear envelope breakdown, START, initiation of DNA replication, progression of DNA replication, termination of DNA replication, centrosome duplication, G2 progression, activation of mitotic or meiotic functions, chromosome condensation, centrosome separation, microtubule nucleation, spindle formation and function, interactions with microtubule motor proteins, chromatid separation and segregation, inactivation of mitotic functions, formation of contractile ring, and cytokinesis functions. In particular, the compounds of the invention may influence certain gene functions such as chrornatin binding, formation of replication complexes, replication licensing, phosphorylation or other secondary modification activity, proteolytic degradation, microtubule binding, actin binding, septin binding, microtubule organising centre nucleation activity and binding to components of cell cycle signalling pathways. In one embodiment of the invention, the compound of the invention is administered in an amount sufficient to inhibit at least one CDK enzyme. Preferably, the compound of the invention is administered in an amount sufficient to inhibit at least one of CDK2 and/or CDK4. Another aspect of the invention relates to the use of a compound of the invention in the preparation of a medicament for treating a viral disorder, such as human cytomegalovirus (HCMV), herpes simplex virus type 1 (HSV-1), human immunodeficiency virus type 1 (HTV-1), and varicella zoster virus (VZV). In a more preferred embodiment of the invention, the compound of the invention is administered in an amount sufficient to inhibit one or more of the host cell CDKs involved in viral replication, i.e. CDK2, CDK7, CDKS, and CDK9 [23]. As defined herein, an anti-viral effect within the scope of the present invention may be demonstrated by the ability to inhibit CDK2, CDK7, CDKS or CDK9. In a particularly preferred embodiment, the invention relates to the use of one or more compounds of the invention in the treatment of a viral disorder which is CDK dependent or sensitive. CDK dependent disorders are associated with an above normal level of activity of one or more CDK enzymes. Such disorders preferably associated with an abnormal level of activity of CDK2, CDK7, CDK8 and/or CDK9. A CDK sensitive disorder is a disorder in which an aberration in the CDK level is not the primary cause, but is downstream of the primary metabolic aberration. In such scenarios, CDK2, CDK7, CDK8 and/or CDK9 can be said to be part of the sensitive metabolic pathway and CDK inhibitors may therefore be active in treating such disorders. A further aspect of the invention relates to a method of treating a CDK-dependent disorder, said method comprising administering to a subject in need thereof, a compound according to the invention, or a pharmaceutically acceptable salt thereof, as defined above in an amount sufficient to inhibit a cyclin dependent kinase. Preferably, the CDK-dependent disorder is a viral disorder or a proliferative disorder, more preferably cancer. Another aspect of the invention relates to the use of compounds of the invention, or pharmaceutically accetable salts thereof, in the preparation of a medicament for treating diabetes. In a particularly preferred embodiment, the diabetes is type n diabetes. GSK3 is one of several protein kinases that phosphorylate glycogen synthase (GS). The stimulation of glycogen synthesis by insulin in skeletal muscle results from the dephosphorylation and activation of GS. GSKS's action on GS thus results in the latter's deactivation and thus suppression of the conversion of glucose into glycogen in muscles. Type n diabetes (non-insulin dependent diabetes mellitus) is a multi-factorial disease. Hyperglycaemia is due to insulin resistance in the liver, muscles, and other tissues, coupled with impaired secretion of insulin. Skeletal muscle is the main site for insulin-stimulated glucose uptake, there it is either removed from circulation or converted to glycogen. Muscle glycogen deposition is the main determinant in glucose homeostasis and type n diabetics have defective muscle glycogen storage. There is evidence that an increase in GSK3 activity is important in type II diabetes [24]. Furthermore, it has been demonstrated that GSK3 is over-expressed in muscle cells of type n diabetics and that an inverse correlation exists between skeletal muscle GSK3 activity and insulin action [25]. GSK3 inhibition is therefore of therapeutic significance in the treatment of diabetes, particularly type II, and diabetic neuropathy. It is notable that GSK3 is known to phosphorylate many substrates other than GS, and is thus involved in the regulation of multiple biochemical pathways. For example, GSK is highly expressed in the central and peripheral nervous systems. Preferably, the compound is administered in an amount sufficient to inhibit GSK, more preferably GSK3, more preferably still GSK30. Another aspect of the invention therefore relates to the use of compounds of the invention, or pharmaceutically acceptable salts thereof, in the preparation of a medicament for treating a CNS disorders, for example neurodegenerative disorders. Preferably, the CNS disorder is Alzheimer's disease. Tau is a GSK-3 substrate which has been implicated in the etiology of Alzheimer's disease. In healthy nerve cells, Tau co-assembles with tubulin into microtubules. However, in Alzheimer's disease, tau forms large tangles of filaments, which disrupt the microtubule structures in the nerve cell, thereby impairing the transport of nutrients as well as the transmission of neuronal messages. Without wishing to be bound by theory, it is believed that GSK3 inhibitors may be able to prevent and/or reverse the abnormal hyperphosphorylation of the microtubule-associated protein tau that is an invariant feature of Alzheimer's disease and a number of other neurodegenerative diseases, such as progressive supranuclear palsy, corticobasal degeneration and Pick's disease. Mutations in the tau gene cause inherited forms of frontotemporal dementia, further underscoring the relevance of tau protein dysfunction for the neurodegenerative process [26]. Another aspect of the invention relates to the use of compounds of the invention, or pharmaceutically acceptable salts thereof, in the preparation of a medicament for treating bipolar disorder. Yet another aspect of the invention relates to the use of compounds of the invention, or pharmaceutically acceptable salts thereof, in the preparation of a medicament for treating a stroke. Reducing neuronal apoptosis is an important therapeutic goal in the context of head trauma, stroke, epilepsy, and motor neuron disease [27]. Therefore, GSK3 as a proapoptotic factor in neuronal cells makes this protein kinase an attractive therapeutic target for the design of inhibitory drugs to treat these diseases. Yet another aspect of the invention relates to the use of compounds of the invention, or pharmaceutically acceptable salts thereof, in the preparation of a medicament for treating alopecia. '" Hair growth is controlled by the Wnt signalling pathway, in particular Wnt-3. In tissueculture model systems of the skin, the expression of non-degradable mutants of p-catenin leads to a dramatic increase in the population of putative stem cells, which have greater proliferative potential [28]. This population of stem cells expresses a higher level of noncadherin- associated p-catenin [29], which may contribute to their high proliferative potential. Moreover, transgenic mice overexpressing a truncated p-catenin in the skin undergo de novo hair-follicle morphogenesis, which normally is only established during embryogenesis. The ectopic application of GSK3 inhibitors may therefore be therapeutically useful in the treatment of baldness and in restoring hair growth following chemotherapy-induced, alopecia. A further aspect of the invention relates to a method of treating a GSK3-dependent disorder, said method comprising administering to a subject in need thereof, a compound according to the invention, or a pharmaceutically acceptable salt thereof, as defined above in an amount sufficient to inhibit GSK3. Preferably, the GSK3-dependent disorder is diabetes. Preferably, the compound of the invention, or pharmaceutically acceptable salt thereof, is administered in an amount sufficient to inhibit GSK3j3. In one embodiment of the invention, the compound of the invention is administered in an amount sufficient to inhibit at least one PLK enzyme. The polo-Eke khiases (PLKs) constitute a family of serine/threorune protein kinases. Mitotic Drosophila melanogaster mutants at the polo locus display spindle abnormalities [30] and polo was found to encode a mitotic kinase [31]. In humans, there exist three closely related PLKs [32]. They contain a highly homologous amino-terrninal catalytic kinase domain and their carboxyl termini contain two or three conserved regions, the polo boxes. The function of the polo boxes remains incompletely understood but they are implicated in the targeting of PLKs to subcellular compartments [33,34], mediation of interactions with other proteins [35], or may constitute part of an autoregulatory domain [36]. Furthermore, the polo box-dependent PLK1 activity is required for proper metaphase/anaphase transition and cytokinesis [37,38]. Studies have shown that human PLKs regulate some fundamental aspects of mitosis [39,40]. In particular, PLK1 activity is believed to be necessary for the functional maturation of centrosomes in late G2/early prophase and subsequent establishment of a bipolar spindle. Depletion of cellular PLK1 through the small interfering RNA (siRNA) technique has also confirmed that this protein is required for multiple mitotic processes and completion of cytokinesis [41]. In a more preferred embodiment of the invention, the compound of the invention is administered in an amount sufficient to inhibit PLK1. Of the three human PLKs, PLK1 is the best characterized; it regulates a number of cell division cycle effects, including the onset of mitosis [42,43], DNA-damage checkpoint activation [44,45], regulation of the anaphase promoting complex [46-48], phosphorylation of the proteasome [49], and centrosome duplication and maturation [50]. Specifically, initiation of mitosis requires activation of M-phase promoting factor (MPF), the complex between the cyclin dependent kinase CDK1 and B-type cyclins [51]. The latter accumulate during the S and G2 phases of the cell cycle and promote the inhibitory phosphorylation of the MPF complex by WEE1, MIK1, and MYT1 kinases. At the end of the G2 phase, corresponding dephosphorylation by the dual-specificity phosphatase CDC25C triggers the activation of MPF [52]. In interphase, cyclin B localizes to the cytoplasm [53], it then becomes phosphorylated during prophase and this event causes nuclear translocation [54,55]. The nuclear accumulation of active MPF during prophase is thought to be important for initiating M-phase events [56]. However, nuclear MPF is kept inactive by WEE1 unless counteracted by CDC25C. The phosphatase CDC25C itself, localized to the cytoplasm during interphase, accumulates in the nucleus in prophase [57- 59]. The nuclear entry of both cyclin B [60] and CDC25C [61] are promoted through phosphorylation by PLK1 [43]. This kinase is an important regulator of M-phase initiation. In one particularly preferred embodiment, the compounds of the invention are ATPantagonistic inhibitors of PLK1. In the present context ATP antagonism refers to the ability of an inhibitor compound to diminish or prevent PLK catalytic activity, i.e. phosphotransfer from ATP to a macromolecular PLK substrate, by virtue of reversibly or irreversibly binding at the enzyme's active site in such a manner as to impair or abolish ATP binding. In another preferred embodiment, the compound of the invention is administered in an amount sufficient to inhibit PLK2 and/or PLK3. Mammalian PLK2 (also known as SNK) and PLK3 (also known as PRK and FNK) were originally shown to be immediate early gene products. PLK3 kinase activity appears to peak during late S and G2 phase. It is also activated during DNA damage checkpoint activation and severe oxidative stress. PLK3 also plays an important role in the regulation of microtubule dynamics and centrosome function in the cell and deregulated PLK3 expression results in cell cycle arrest and apoptosis [62]. PLK2 is the least well understood homologue of the three PLKs. Both PLK2 and PLK3 may have additional important postmitotic functions [35]. A further aspect of the invention relates to a method of treating a PLK-dependent disorder, said method comprising administering to a subject hi need thereof, a compound according to the invention, or a pharmaceutically acceptable salt thereof, as defined above in an amount sufficient to inhibit PLK. Preferably, the PLK-dependent disorder is a proliferative disorder, more preferably cancer. Preferably, the compound of the invention, or pharmaceutically acceptable salt thereof, is administered in an amount sufficient to inhibit aurora kinase. A further aspect of the invention relates to a method of treating an aurora kinase-dependent disorder, said method comprising administering to a subject in need thereof, a compound according to the invention, or a pharmaceutically acceptable salt thereof, as defined above in an amount sufficient to inhibit aurora kinase. Preferably, the aurora kinase dependent disorder is a viral disorder as defined above. PHARMACEUTICAL COMPOSITIONS Another aspect of the invention relates to a pharmaceutical composition comprising a compound of the invention as defined above admixed with one or more pharmaceutically acceptable diluents, excipients or carriers. Even though the compounds of the present invention (including their pharmaceutically acceptable salts, esters and pharmaceutically acceptable solvates) can be administered alone, they will generally be administered in admixture with a pharmaceutical carrier, excipient or diluent, particularly for human therapy. The pharmaceutical compositions may be for human or animal usage in human and veterinary medicine. Examples of such suitable excipients for the various different forms of pharmaceutical compositions described herein may be found in the "Handbook of Pharmaceutical Excipients, 2nd Edition, (1994), Edited by A Wade and PJ Weller. Acceptable carriers or diluents for therapeutic use are well known in the pharmaceutical art, and are described, for example, in Remington's Pharmaceutical Sciences, Mack Publishing Co. (A. R. Gennaro edit. 1985). Examples of suitable carriers include lactose, starch, glucose, methyl cellulose, magnesium stearate, mannitol, sorbitol and the like. Examples of suitable diluents include ethanol, glycerol and water. The choice of pharmaceutical carrier, excipient or diluent can be selected with regard to the intended route of administration and standard pharmaceutical practice. The pharmaceutical compositions may comprise as, or in addition to, the carrier, excipient or diluent any suitable binder(s), lubricant(s), suspending agent(s), coating agent(s), solubilising agent(s). Examples of suitable binders include starch, gelatin, natural sugars such as glucose, anhydrous lactose, free-flow lactose, beta-lactose, com sweeteners, natural and synthetic gums, such as acacia, tragacanth or sodium alginate, carboxymethyl cellulose and polyethylene glycol. Examples of suitable lubricants include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride and the like. Preservatives, stabilizers, dyes and even flavoring agents may be provided in the pharmaceutical composition. Examples of preservatives include sodium benzoate, sorbic acid and esters of p-hydroxybenzoic acid. Antioxidants and suspending agents may be also used. SALTS/ESTERS The compounds of the invention can be present as salts or esters, hi particular pharmaceutically acceptable salts or esters. Pharmaceutically acceptable salts of the compounds of the invention include suitable acid addition or base salts thereof. A review of suitable pharmaceutical salts may be found in Berge et al, J Pharm Sci, 66, 1-19 (1977). Salts are formed, for example with strong inorganic acids such as mineral acids, e.g. sulphuric acid, phosphoric acid or hydrohalic acids; with strong organic carboxylic acids, such as alkanecarboxylic acids of 1 to 4 carbon atoms which are unsubstiruted or substituted (e.g., by halogen), such as acetic acid; with saturated or unsaturated dicarboxylic acids, for example oxalic, malonic, succinic, maleic, fumaric, phthalic or tetraphthalic; with hydroxycarboxylic acids, for example ascorbic, glycolic, lactic, malic, tartaric or citric acid; with aminoacids, for example aspartic or glutamic acid; with benzoic acid; or with organic sulfonic acids, such as (Ci-C4)-alkyl- or aryl-sulfonic acids which are unsubstituted or substituted (for example, by a halogen) such as methane- or p-toluene sulfonic acid. Esters are formed either using organic acids or alcohols/hydroxides, depending on the functional group being esterified. Organic acids include carboxylic acids, such as alkanecarboxylic acids of 1 to 12 carbon atoms which are unsubstituted or substituted (e.g., by halogen), such as acetic acid; with saturated or unsaturated dicarboxylic acid, for example oxalic, malonic, succinic, maleic, fumaric, phthalic or tetraphthalic; with hydroxycarboxylic acids, for example ascorbic, glycolic, lactic, malic, tartaric or citric acid; with aminoacids, for example aspartic or ghitamic acid; with benzoic acid; or with organic sulfonic acids, such as (Ci-C^-alkyl- or aryl-sulfonic acids which are unsubstituted or substituted (for example, by a halogen) such as methane- or p-toluene sulfonic acid. Suitable hydroxides include inorganic hydroxides, such as sodium hydroxide, potassium hydroxide, calcium hydroxide, aluminium hydroxide. Alcohols include alkanealcohols of 1-12 carbon atoms which may be unsubstituted or substituted, e.g. by a halogen). ENANTIOMERS/TAUTOMERS In all aspects of the present invention previously discussed, the invention includes, where appropriate all enantiomers and tautomers of compounds of the invention. The man skilled in the art will recognise compounds that possess an optical properties (one or more chiral carbon atoms) or tautomeric characteristics. The corresponding enantiomers and/or tautomers may be isolated/prepared by methods known in the art. STEREO AND GEOMETRIC ISOMERS Some of the compounds of the invention may exist* as stereoisomers and/or geometric isomers - e.g. they may possess one or more asymmetric and/or geometric centres and so may exist in two or more stereoisomeric and/or geometric forms. The present invention contemplates the use of all the individual stereoisomers and geometric isomers of those agents, and mixtures thereof. The terms used in the claims encompass these forms, provided said forms retain the appropriate functional activity (though not necessarily to the same degree). The present invention also includes all suitable isotopic variations of the agent or pharmaceutically acceptable salt thereof. An isotopic variation of an agent of the present invention or a pharmaceutically acceptable salt thereof is defined as one hi which at least one atom is replaced by an atom having the same atomic number but an atomic mass different from the atomic mass usually found in nature. Examples of isotopes that can be incorporated into the agent and pharmaceutically acceptable salts thereof include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulphur, fluorine and chlorine such as 2H, 3H, 13C, 14C, 15N, 170,180,31P, 32P, 35S, 18F and 36C1, respectively. Certain isotopic variations of the agent and pharmaceutically acceptable salts thereof, for example, those in which a radioactive isotope such as 3H or 14C is incorporated, are useful in drug and/or substrate tissue distribution studies. Tritiated, i.e., 3H, and carbon-14, i.e., 14C, isotopes are particularly preferred for then: ease of preparation and detectability. Further, substitution with isotopes such as deuterium, i.e., 2H, may afford certain therapeutic advantages resulting from greater metabolic stability, for example, increased hi vivo half-life or reduced dosage requirements and hence may be preferred in some circumstances. Isotopic variations of the agent of the present invention and pharmaceutically acceptable salts thereof of this invention can generally be prepared by conventional procedures using appropriate isotopic variations of suitable reagents. SOLVATES The present invention also includes the use of solvate forms of the compounds of the present invention. The terms used in the claims encompass these forms. POLYMORPHS The invention furthermore relates to the compounds of the present invention hi their various crystalline forms, polymorphic forms and (an)hydrous forms. It is well established within the pharmaceutical industry that chemical compounds may be isolated in any of such forms by slightly varying the method of purification and or isolation form the solvents used in the synthetic preparation of such compounds. PRODRUGS The invention further includes the compounds of the present invention in prodrug form. Such prodrugs are generally compounds of the invention wherein one or more appropriate groups have been modified such that the modification may be reversed upon administration to a human or mammalian subject. Such reversion is usually performed by an enzyme naturally present in such subject, though it is possible for a second agent to be administered together with such a prodrug in order to perform the reversion in vivo. Examples of such modifications include ester (for example, any of those described above), wherein the reversion may be carried out be an esterase etc. Other such systems will be well known to those skilled in the art. ADMINISTRATION The pharmaceutical compositions of the present invention may be adapted for oral, rectal, vaginal, parenteral, intramuscular, intraperitoneal, intraarterial, intrathecal, intrabronchial, subcutaneous, intradermal, intravenous, nasal, buccal or sublingual routes of administration. For oral administration, particular use is made of compressed tablets, pills, tablets, gellules, drops, and capsules. Preferably, these compositions contain from 1 to 250 mg and more preferably from 10-100 mg, of active ingredient per dose. Other forms of administration comprise solutions or emulsions which may be injected intravenously, intraarterially, intrathecally, subcutaneously, intradermally, intraperitoneally or intramuscularly, and which are prepared from sterile or sterilisable solutions. The pharmaceutical compositions of the present invention may also be in form of suppositories, pessaries, suspensions, emulsions, lotions, ointments, creams, gels, sprays, solutions or dusting powders. An alternative means of transdermal administration is by use of a skin patch. For example, the active ingredient can be incorporated into a cream consisting of an aqueous emulsion of polyethylene glycols or liquid paraffin. The active ingredient can also be incorporated, at a concentration of between 1 and 10% by weight, into an ointment consisting of a white wax or white soft paraffin base together with such stabilisers and preservatives as may be required. f Injectable forms may contain between 10-1000 mg, preferably between 10-250 mg, of active ingredient per dose. Compositions may be formulated in unit dosage form, i.e., in the form of discrete portions containing a unit dose, or a multiple or sub-unit of a unit dose. DOSAGE A person of ordinary skill in the art can easily determine an appropriate dose of one of the instant compositions to administer to a subject without undue experimentation. Typically, a physician will determine the actual dosage which will be most suitable for an individual patient and it will depend on a variety of factors including the activity of the specific compound employed, the metabolic stability and length of action of that compound, the age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, the severity of the particular condition, and the individual undergoing therapy. The^ dosages disclosed herein are exemplary of the average case. There can of course be individual instances where higher or lower dosage ranges are merited, and such are within the scope of this invention. Depending upon the need, the agent may be administered at a dose of from 0.01 to 30 mg/kg body weight, such as from 0.1 to 10 mg/kg, more preferably from 0.1 to 1 mg/kg body weight. In an exemplary embodiment, one or more doses of 10 to 150 mg/day will be administered to the patient. COMBINATIONS In a particularly preferred embodiment, the one or more compounds of the invention are administered in combination with one or more other therapeutically active agents, for example, existing drugs available on the market. In such cases, the compounds of the invention may be administered consecutively, simultaneously or sequentially with the one or more other active agents. By way of example, it is known that anticancer drugs in general are more effective when used in combination.- In particular, combination therapy is desirable in order to avoid an overlap of major toxicities, mechanism of action and resistance mechanism(s). Furthermore, it is also desirable to administer most drugs at their maximum tolerated doses with minimum time intervals between such doses. The major advantages of combining chemotherapeutic drugs are that it may promote additive or possible synergistic effects through biochemical interactions and also may decrease the emergence of resistance in early tumor cells which would have been otherwise responsive to initial chemotherapy with a single agent. An example of the use of biochemical interactions in selecting drug combinations is demonstrated by the administration of leucovorin to increase the binding of an active intracellular metabolite of 5-fluorouracil to its target, thymidylate synthase, ' thus increasing its cytotoxic effects. Numerous combinations are used in current treatments of cancer and leukemia. A more extensive review of medical practices may be found in "Oncologic Therapies" edited by E. E. Yokes and H. M. Golomb, published by Springer. Beneficial combinations may be suggested by studying the growth inhibitory activity of the test compounds with agents known or suspected of being valuable in the treatment of a particular cancer initially or cell lines derived from that cancer. This procedure can also be used to determine the order of administration of the agents, i.e. before, simultaneously, or after delivery. Such scheduling may be a feature of all the cycle acting agents identified herein. ASSAYS Another aspect of the invention relates to the use of a compound of the invention in an assay for identifying further candidate compounds capable of inhibiting one or more protein kinases. Another aspect of the invention relates to the use of a compound of the invention in an assay for identifying further candidate compounds capable of inhibiting one or more cyclin dependent kinases, aurora kinase, GSK and PLK. Preferably, the assay is a competitive binding assay. More preferably, the competitive binding assay comprises contacting a compound of the invention with a protein kinase and a candidate compound and detecting any change in the interaction between the compound of the invention and the protein kinase. One aspect of the invention relates to a process comprising the steps of: (a) performing an assay method described hereinabove;v (b) identifying one or more ligands capable of binding to a ligand binding domain; and (c) preparing a quantity of said one or mote ligands. Another aspect of the invention provides a process comprising the steps of: (a) performing an assay method described hereinabove; (b) identifying one or more ligands capable of binding to a ligand binding domain; and (c) preparing a pharmaceutical composition comprising said one or more ligands. Another aspect of the invention provides a process comprising the steps of: (a) performing an assay method described hereinabove; (b) identifying one or more ligands capable of binding to a ligand binding domain; (c) modifying said one or more ligands capable of binding to a ligand binding domain; (d) performing the assay method described hereinabove; (e) optionally preparing a pharmaceutical composition comprising said one or more ligands. The invention also relates to a ligand identified by the method described hereinabove. Yet another aspect of the invention relates to a pharmaceutical composition comprising a ligand identified by the method described hereinabove. Another aspect of the invention relates to the use of a ligand identified by the method described hereinabove in the preparation of a pharmaceutical composition for use in the treatment of proliferative disorders, viral disorders, a CNS disorder, stroke, alopecia and diabetes. Preferably, said candidate compound is generated by conventional SAR modification of a compound of the invention. As used herein, the term "conventional SAR modification" refers to standard methods known in the art for varying a given compound by way of chemical derivatisation. The above methods may be used to screen for a ligand useful as an inhibitor of one or more protein kinases. SYNTHESIS The compo-.-nds of the invention can be prepared by any method known in the art. Two convenient ••• ,-nthetic routes are shown below in Scheme 1: (Figure Removed) Scheme 1 Palladium-catalysed cross-coupling of phenyl boronic acids (HI, Y = B(OH)2) or their derivatives with 2,4-dihalogenated pyrimidines (II; e.g. X1 = X2 = Cl) [63, 64] affords 4- arylated 2-halogenopyrimidines IV, which are aminated with anilines V. Alternatively, acetophenones VI are acylated, e.g. with R6COC1, to provide the diketones VII. These in turn are enaminated to VIII [65], followed by condensation with arylguanidines IX [66]. A further aspect of the invention therefore relates to a process for preparing a compound of formula I as defined above, said process comprising the steps of: (Figure Removed) (i) reacting a phenyl boronic acid of formula HI with a 2,4-dihalogenated pyrimidine of formula II to form a compound of formula IV; and (ii) reacting said compound of formula IV with an aniline of formula V to form a compound of formula I. Yet another aspect of the invention relates to a process for preparing a compound of formula I as defined above, said process comprising the steps of: (Figure Removed) (i) reacting a compound of formula VI with R6COC1, where R6 is as defined above, to form a compound of formula VII; 44 (ii) converting said compound of formula VII to a compound of formula VIII; and (iii) reacting said compound of formula Vffl with a compound of formula DC to form a compound of formula I. EXAMPLES Example 1 General HPLC retention times (t/?) were measured using Vydac 218TP54 columns (Cig reversedphase stationary phase; 4.5 x 250 mm columns), eluted at 1 mL/min with a linear gradient of acetonitrile in water (containing 0.1 % CFsCOOH) as indicated, followed by isocratic elution, UV monitors (254 nm) were used. All purification work, unless otherwise stated, was performed using silica gel 60A (particle size 35-70 micron. 1H-NMR spectra were recorded using 500 MHz instrument. Chemical shifts are given in ppm using TMS as standard and coupling constants (J) are stated in Hz. Mass spectra were recorded under positive or negative ion electrospray conditions. The structures of selected compounds of the invention are shown in Table 1. Example 2 {4-(3-Amino-phenyl)-pyrimidin-2-ylJ-[4-(2-methoxy-ethoxy)-pkenyl]-amine(3) A mixture of 3-aminoacetophenone (1.35 g, 10 mmol) and AyV-dimethylfonnamide dimethylacetal (3.99 mL, 30 mmol) was heated at 102 °C for 8 h. On cooling, the reaction mixture was evaporated to dryness. The yellow residue was collected and washed with EtOAc/PE (1:5) to yield l-(3-ammo-phenyl)-3-dimethylarnino-propenone as an orange solid (1.85 g, 97 %). 'H-NMR (CDC13): S 2.41 (s, 6H, CH3), 5.75 (d, 1H, J= f2.0 Hz, CH), 6.88 (d, 1H, J= 8.0 Hz, Ph-H), 6.98 (d, 1H, J= 8.0 Hz, Ph-H), 7.14 (t, 1H, /= 8.0 Hz, Ph-H), 7.38 (s, 1H, Ph-H), 7.57 (d, 1H, J= 12.0 Hz, CH); MS (ESI*) m/z 191.22 [M+Hf, CnHuNaO requires 190.24. An aliquot of this material (0.73 g, 38.1 ramol), dissolved in 2-methoxylethanol (3 mL), was treated with Af-(4-hydroxy-phenyl)-guanidine nitrate (0.82 g, 38.1 mmol), which was prepared by condensation of 4-amino-phenol and aqueous cyanamide solution in the presence of nitric acid, and NaOH (0.15 g, 38.1 mmol). After refluxing overnight, the reaction mixture was concentrated and the residue was purified by SiO2 gel chromatography (EtOAc/PE, 5:1) to afford the title compound (85 mg, 7 %). 'H-NMR (CD3OD): S 3.36 (s, 3H OCH3), 3.58 (t, 2H, J= 5.0 Hz, CH2), 4.13 (t, 2H, J= 5.0 Hz, CH2), 6.80 (d, 2H, J= 8.0 Hz, Ph-H), 6.86 (d, 2H, /= 8.0 Hz, Ph-H), 7.12 (d, IH, J = 5.0 Hz, pyrimidine-H), 7.22 (t, IH, /= 8.0 Hz, Ph-H), 7.41 (d, IH, J= 9.0 Hz, Ph-H), 7.45 (s, IH, Ph-H), 7.47 (d, IH, J= 8.0 Hz, Ph-H), 8.32 (d, IH, /= 5.0 Hz, pyrimidine-H); MS (ESI1") m/z 336.80 [M]; Ci9H2oN4O2 requires 336.39. Example 3 N-Ethyl-N-{3-[2-(4-hydroty-phenylamino)-pyrimidin-4-yl]-phenyl}-acetamide(\fy Acetamidoacetophenone (0.2 g, 1.13 mmol) in Me2CO (2 mL) was treated with KOH (63 mg, 1.13 mmol) and then iodoethane (0.45 mL, 5.64 mmol). After stirring at room temperature overnight the reaction mixture was concentrated to dryness. The residue was redissolved in EtOAc and was washed with H2O and brine, and was dried on MgSC>4. The solvent was evaporated to yield A^(3-acetyl-phenyl)-JV-ethyl-acetamide as an orange powder (0.23 g, 100 %): mp 203-204 °C; !H-NMR (CD3OD): 81.11 (t, 3H, J= 7.0 Hz, CH3), 1.82 (s, 3H, CH3), 3.31 (s, 3H, CH3), 3.77 (q, 2H, /= 7.0, 14.0 Hz, CH2) 7.56 (d, IH, J= 8.0 Hz, Ph-H), 7.65 (t, IH, /= 8 Hz, Ph-H), 7.88 (s, IH, Ph-H) and 8.06 (d, IH, J = 8 Hz, Ph-H); MS (ESI*) m/z 205.91 [M], Ci2Hi5Nq2 requires 205.25. This material (0.23g, 1.13 mmol), redissolved in MeCN (2 mL), was treated with N,Ndimethylformamide dimethylacetal (150 uL, 1.12 mmol) at 180 °C for 10 min in a microwave reactor (SmithCreator, Personal Chemistry Ltd.). The solvent was evaporated and the residue was filtered and washed with EtOAc/PE (1:3) to afford 7V-[3-(3- drniemylammo-acryloyl)-phenyl]-N-ethyl-acetamide as an orange solid (0.30 g, 100 %). 'H-NMR (CD3OD): Sl.ll (t, 3H, J= 7.0 Hz, CH3), 1.82 (s, 3H, CH3), 2.04 (s, 6H, CH3), 3.76 (q, 2H, /= 7.0,14.0 Hz, CH2), 5.87 (d, IH, J= 12.0 Hz, CH), 7.39 (d, IH, J= 8.0 Hz, Ph-H), 7.55 (t, IH, J = 8.0 Hz, 5-H), 7.76 (s, IH, Ph-H), 7.89 (d, IH, J= 12.0 Hz, CH), 7.93 (d, IH, J = 8.0 Hz, Ph-H); MS (ESf) m/z 261.32 [M+H]+, CiSH2oN202 requires 260.33. A solution of this material (0.228 g, 0.88 mmol), 4-hydroxy-phenyl guanidine nitrate (0.188 g, 0.88 mmol) and NaOH (35 mg, 0.88 mmol) in MeCN (2 mL) was heated at 190 °C for 15 min in the microwave reactor. The solvent was evaporated and the residue was purified hy SiOa gel chromatography (EtOAc/PE, 1:1) to afford the title compound as a yellow solid (117 mg, 38 %). !H-NMR (CD3OD): 8 1.16 (t, 3H, J= 7 Hz, CH3), 3.35 (s, 3H, CH3), 3.38 (q, 2H, J= 7.0, 14.0 Hz, CH2), 6.77 (d, 2H, J= 9.0 Hz, Ph-H), 7.27 (d, IH, J= 5.0 Hz, pyrimidine-H), 7.42 (d, IH, J= 8.0 Hz, Ph-H), 7.48 (d, 2H, /= 9.0 Hz, Ph-H), 7.62 (t, IH, 7= 8.0 Hz, Ph-H), 8.6 (s, IH, Ph-H), 8.14 (d, IH, J= 8.0 Hz, Ph-H), 8.41 (d, IH, J= 5.0 Hz, pyrimidine-H). Example 4 N-{3-[2-(4-Hydroxy-phenylamino)-pyrimidin-4-yl]-phenyl}-acetamide(ll) This compound was obtained by treatment of A/-[3-(3-dimethylamrno-acryloyl)-phenyl]- acetamide and 4-hydroxy-phenyl guanidine nitrate in MeCN: 98 mg yellow solid (30 %). 'H-NMR (CD3OD): £3.32 (s, m, CH3), 6.79 (d, 2H, J= 9.0 Hz, Ph-H), 7.18 (d, IH, J = 5.0 Hz, pyrimidine-H), 7.44 (t, IH, J= 8.0 Hz, Ph-H), 7.50 (d, 2H, J= 9.0 Hz, Ph-H), 7.65 (d, IH, J= 9.0 Hz, Ph-H), 7.84 (d, IH, J = 8.0 Hz, Ph-H), 8.35 (s, IH, Ph-H), 8.37 (d, IH, /= 5.0 Hz, pyrimidine-H). JV-[3-(3-Dimethylamino-acryloyl)-phenyl]-acetamide was prepared by treatment o acetyl-phenyl)-acetamide with WV-dimethylformamide dimethylacetal (93 %): JH-NMR (CD3OD): S 2.14 (s, 6H, CH3), 2.58 (s, 3H, CH3), 5.79 (d, IH, J= 12.0 Hz, CH), 7.37 (t, IH, J= 8.0 Hz, Ph-H), 7.58 (d, IH, J= 8.0 Hz, Ph-H), 7.7 (d, J= 8.0 Hz, IH, Ph-H), 7.83 (d, /= 12.0 Hz, IH, CH), 8.02 (s, IH, 2-H); MS (ESf) m/z 233.20 [M+H]+, requires 232.28. Example 5 [4-(3-Imidazol-l-ylmethyl-phenyl)-pyi'imidin-2-yl]-(3-nitro-phenyl)-amine(29) A solution of 1-wz-tolyl-ethanone (5.0 g, 37.3 mmol) in anh. MeCN (45 mL) was treated with TV-bromosuccinimide (6.63 g, 37.3 mmol) and benzoyl peroxide (9.02 g, 37.3 mmol). The reaction mixture was heated at 80 °C for 6 h. On cooling, the mixture was concentrated and the resulting syrup was dissolved in EtaO and treated with NaHCOs. The ethereal layer was washed with brine and dried on MgSO4. The solvent was evaporated and the resulting residue was purified by SiOj gel chromatography (heptane/EtOAc 12:1- 3:1) to afford l-(3-bromomethyl-phenyl)-ethanone (5.5 g, 69 %). ^-NMR (CDC13): £2.54 (s, 3H, CH3), 4.45 (s, 2H, CH2), 7.38 (t, 1H, J= 8.0 Hz, Ph-H), 7.52 (d, 1H, J= 8.0 Hz, Ph- H), 7.81 (d, 1H, J= 8.0 Hz, Ph-H), 7.90 (s, 1H, Ph-H). l//-Imidazole (0.15 g, 2.25 mmol) in anh. DMF (8 mL) was cooled on an ice bath and treated with Cs2CO3 (0.67 g, 2.07 mmol). After stirring for 30 min l-(3-bromomethylphenyl)- ethanone (0.4 g, 1.88 mmol) was added. The reaction mixture was warmed to room temperature and was stirred for 20 h. Ice water was added and the mixture was extracted with Et2O. The combined extracts were washed with brine and dried on MgSO4. The solvent was evaporated and the residue was purified by SiO2 gel chromatography using heptane/EtOAc (12:1-3:1) to afford l-(3-irnidazol-l-ylmethyl-phenyl)-ethanone (0.23 g, 60 %) as a brown syrup. !H-NMR (CDC13) & 2.57 (s, 3H, CH3), 5.16 (s, 2H, CH2), 6.89 (s, 1H, imidazole-H), 7.08 (s, 1H, imidazole-H), 7.30 (d, 1H, J= 8.0 Hz, Ph-H), 7.45 (t, 1H, J= 8.0 Hz, Ph-H), 7.54 (s, 1H, imidazole-H), 7.77 (s, 1H, Ph-H), 7.89 (d, 1H, J = 8.0 Hz, Ph-H). x An aliquot of this material (0.10 g, 0.50 mmol) was treated with A^ TV-dimethyl formamide dimethylacetal (1 mL, 8.39 mmol) at 100 °C for 7 h. On cooling, the reaction mixture was concentrated and the resulting residue was purified by SiO2 chromatography using heptane/EtOAc (3:1-1:10) to afford 3-dimethylamino-l-(3-imidazol-l-ylmethyl-phenyl)- propenone as yellow solid (0.11 g, 83 %). 'H-NMR (CDC13) & 2.88 (s, 3H, CH3), 3.11 (s, 3H, CH3), 5.12 (s, 2H, CH2), 5.61 (d, 1H, /= 12.0 Hz, CH), 6.88 (s, 1H, imidazole-H), 7.04 (s, 1H, imidazole-H), 7.15 (d, 1H, J= 6.0 Hz, Ph-H), 7.35 (t, 1H, J= 7.5 Hz, Ph-H), 7.54 (s, 1H, imidazole-H), 7.71 (s, 1H, Ph-H), 7.75 (m, 2H, Ph-H and CH). A mixture of the latter compound (0.10 g, 0.39 mmol), 3-nitro-phenyl guanidine nitrate (0.11 g, 0.43 rnmol), and NaOH (0.019 g, 0.47 mmol) in 2-methoxylethanol (4 mL) was heated at 125 °C for 20 h. The solvent was evaporated and the residue was purified by SiC^ gel chromatography using EtOAc and EtOAc/MeOH (10:1) to afford the title compound as a yellow solid (0.079 g, 55 %). Anal. RP-HPLC: to = 17 min (0 - 60 % MeCN, purity > 95 %). -NMR (DMSCMg): 55.32 (s, 2H, CH2), 6.91 (s, 1H, imidazole-H), 7.23 (s, 1H, imidazole-H), 7.41 (d, 1H, J= 8.0 Hz, Ph-H), 7.51 (d, J= 5.5 Hz, pyrimidine-H), 7.54 (t, 1H, J= 8.0 Hz, Ph-H), 7.59 (t, 1H, J= 8.0 Hz, Ph-H), 7.81 (m, 2H, Ph-H), 8.05 (d, 1H, J= 8.0 Hz, Ph-H), 8.14 (d, 1H, J= 8.0 Hz, Ph-H), 8.18 (s, 1H, Ph-H), 8.65 (d, 1H, /= 5.5 Hz, pyrimidine-H), 9.14 (s, 1H, imidazole-H), 10.27 (s, 1H, NH). I3C-NMR (DMSO-&): S 60.4, 109.8, 113.1, 116.3, 120.3, 125.3, 126.8, 127.2, 129.5, 130.1, 130.5, 130.6, 137.5, 138.1,139.4,142.6,148.9,160.2,160.4,163.9. MS (ESf) m/z 373.2 [M+H]+, CzoHieNeOz requires 372.38. Example 6 The following compounds were prepared in a similar manner to that described in Example 5 above: (3-Nitro-pkejiyl)-[4-(3-fJt2,4JtriazoI-J-ylmethyl-phenyl)-pyrimidin-2-ylJ-amine(3ff) By treatment of 3-dimethylamino-l-(3-[l,2,4]triazol-l-yhnethyl-phenyl)-propenone and 3- nitro-phenyl guanidine nitrate. Yellow solid (50 %). Anal. RP-HPLC: t/j= 17 min (0 - % MeCN, purity > 95%). ^-NMR (DMSO-rf6): 55.54 (s, 2H, CH2), 7.43 (d, 1H, /= 8.0 Hz, Ph-H), 7.51 (d, 1H, /= 5.0 Hz, pyrimidine-H), 7.54 (t, 1H, J= 8.0 Hz, Ph-H), 7.58 (t, 1H, J= 8.0 Hz, Ph-H), 7.81 (d, 1H, /= 8.0 Hz, Ph-H), 7.98 (s, 1H, Ph-H), 8.07 (d, 1H, /= 8.0 Hz, Ph-H), 8.15 (d, 1H, J = 8.0 Hz, Ph-H), 8.21 (s, 1H, Ph-H), 8.65 (d, 1H, J= 5.0 Hz, pyrimidine-H), 8.70 (s, 1H, triazole-H), 9.11 (s, 1H, triazole-H), 10.27 (s, 1H, NH). MS (ESf) m/z 374.4 [M-l-H]+, CipHistyOz requires 373.37. 49 3-dimethylamino-l-(3-[l,2,4]triazol-l-ylmeihyl-phenyl)-propenone 'H-NMR (DMSO-rfe): 52.89 (s, 3H, CH3), 3.12 (s, 3H, CH3), 5.45 (s, 2H, CH2), 5.76 (d, IH, J= 12.5 Hz, CH), 7.35 (d, IH, J= 8.0 Hz, Ph-H), 7.40 (t, IH, J= 8.0 Hz, Ph-H), 7.70 (d, IH, /= 12.5 Hz, CH), 7.79 (s, IH, Ph-H), 7.82 (d, IH, J= 8.0 Hz, Ph-H), 7.97 {s, IH, triazole-H), 8.67 (s, IH, triazole-H). l-(3-[l, 2,4JTriazol-l -ylmethyl-phenyl)-ethanone 1H-NMR (CDC13): 52.58 (s, 3H, CH3), 5.39 (s, 2H, CH2), 7.45 (d, IH, J= 7.5 Hz, Ph-H), 7.47 (t, IH, J= 7.5 Hz, Ph-H), 7.87 (s, IH, Ph-H), 7.92 (d, IH, J= 7.5 Hz, Ph-H), 7.97 (s, IH, triazole-H), 8.11 (s, IH, triazole-H). {4-f3-(Benzylamino-methyl)-phenylJ-pyri7nidin-2-yl}-(6-chloro-pyridin-3-yl)-amine(4S) By treatment of l-[3-(ben2ylamino-methyl)-phenyl]-3-dimethylamino-propenone and N- (6-chloro-pyridin-3-yl)-guanidine nitrate, which was prepared by condensation of 5-amino- 2-chloropyridine and aqueous cyanamide solution in the presence of HNOs. Yellow solid (35 %). Anal. RP-HPLC: t*= 24 min (0 - 60 % MeCN, purity > 95 %). 'H-NMR (CDC13): 54.30 (m, 2H, CH2), 4.44 (m, 2H, CH2), 7.13 (m, 3H, Ph-H), 7.24-7.28 (m, 4H, Ph-H), 7.37 (d, IH, J= 8.0 Hz, Ph-H), 7.44 (m, 2H, pyrirnidine-H and Ph-H), 7.84 (s, IH, Ph-H), 7.90 (d, IH, /= 8.0 Hz, Ph-H), 8.18 (m, IH, Ph-H), 8.45 (m, 2H, pyrimidine-H and NH), 8.58 (m, IH, NH). MS (ESf) m/z 402.5 [M+H]+, C23H2oClN5 requires 401.89. l-[3-(Beiizylamino-methyl)-phenyl]-3-dimethylamino-propenone 'H-NMR (CDC13): 52.94 (s, 3H, CH3), 3.14 (s, 3H, CH3), 3.79 (s, 2H, CH2), 3.83 (s, 2H, CH2), 5.70 (d, IH, 7= 12.5 Hz, CH), 7.21 (t, IH, J= 7.5 Hz, Ph-H), 7.29 (d, 2H, J= 7.0 Hz, Ph-H), 7.34 (m, 3H, Ph-H), 7.76 (d, IH, J= 7.5 Hz, Ph-H), 7.80 (d, IH, /= 12.5 Hz, CH), 7.87 (s, IH, Ph-H). 50 l-[3-(Benzylamino-methyl)-phenyl]-ethanone 'H-NMR (CDC13): 52.61 (s, 3H, CH3), 3.82 (s, 2H, CH2), 3.86 (s, 2H, CH2), 7.26 (m, 4H, Ph-H), 7.34 (m, 1H, Ph-H), 7.42 (t, 1H, J = 7.5 Hz, Ph-H), 7.58 (d, 1H, /= 7.5 Hz, Ph-H), 7.85 (d, 1H, J= 7.5 Hz, Ph-H), 7.94 (s, 1H, Ph-H). 3-{4-[3-(Bmzyla7nino-methyl)-phenylJ-pyrimidin-2-ylamino}-phenol(28) By treatment of l-[3-(benzylamino-methyl)-phenyl]-3-dimethylamuio-propenone and N- (3-hydroxy-phenyl)-guanidine nitrate. Yellow solid (10 %). Anal. RP-HPLC: tj?= 11 min (10-70 % MeCN, purity > 95 %). 'H-NMR (DMSO-J6): £4.58 (s, 2H, CH2), 6.37 (d, 2H, J = 7.5 Hz, Ph-H), 7.05 (t, 1H, J = 8.0 Hz, Ph-H), 7.34 (m, 2H, Ph-H), 7.47 (m, 2H, pyrimidine-H and Ph-H), 8.03 (m, 1H, Ph-H), 8.11 (s, 1H, Ph-H), 8.52 (d, 1H, J= 5.5 Hz, pyrimidine-H), 9.54 (s, 1H, NH). (6-Methoxy-pyridin-3-yl)-[4-(3-[l,2,4]triazol-l-ylmethyl-phenyl)-pyrimidin-2-yl]^mme (50) By treatment of 3-dimemylamino-l-(3-[l,2,4]triazol-l-yhnethyl-phenyl)-propenone and N- (6-methoxy-pyridin-3-yl)-guanidine nitrate. Yellow solid (54 %). Anal. RP-HPLC: t« = 12 min (10 - 70 % MeCN, purity > 95 %). 'H-NMR (CD3OD): S3.91 (s, 3H, CH3), 5.54 (s, 2H, CH2), 6.25(d, 1H, J= 9.0 Hz, Ph-H), 7.26 (d, 1H, J= 5.0 Hz, pyrimidine-H), 7.45 (d, 1H, J= 7.0 Hz, Ph-H), 7.51 (t, 1H, J = 7.0, 8.0 Hz, Ph-H), 8.03 (m, 2H, triazole-H and Ar- H), 8.07 (m, 2H, Ar-H), 8.42 (d, 1H, J= 5.0 Hz, pyrimidine-H), 8.50 (d, 1H, J= 5.0 Hz, Ar-H), 8.61 (s, 1H, triazoe-H). MS (ESf) m/z 360.3 [M+H]+, Ci9Hi7N7O requires 359.38. (4-Morpholin-4-yl-phenyl)-[4-(3-[l,2,4]tnazol-l-ylmethyl-phenyl)-pyrimidin-2-yl]-amine (32) By treatment of 3-dimethylamino-l-(3-[l,2,4]triazol-l-yhnethyl-phenyl)-propenone and N- (4-morpholin-4-yl-phenyl)-guanidine nitrate. Yellow solid (44 %). Anal. RP-HPLC: t« = 11 min (10 - 70 % MeCN, purity > 9 5%). ^-NMR (CD3OD): 63.12 (t, 4H, 7= 4.0, 5.0 Hz, CH2), 3.85 (t, 4H, J= 4.5, 5.0 Hz, CH2), 5.53 (s, 2H, CH2), 7.00 (d, 2H, J= 9.0 Hz, Ph-H), 7.22 (d, 1H, J= 5.0 Hz, pyrimidine-H), 7.46 (d, 1H, J= 7.0 Hz, Ph-H), 7.51 (t, 1H, 51 J = 7.0, 8.0 Hz, Ph-H), 7.59 (d, IH, Ph-H), 8.02 (s, IH, triazole-H), 8.07 (m, IH, Ph-H), 8.39 (d, IH, /= 5.0 Hz, pyrimidine-H), 8.61 (s, IH, triazol-H). MS (ESI*) m/z 414.4 [M+Hf , CuHzaNyO requires 413.48. 4-[4-(3-[l,2,4]Triazol-l-ylmethyl-phenyl)-pyrimidin-2-ylamino]-phenol(33) By treatment of 3-dimethylamino-l-(3-[l,2,4]triazol-l-yknethyl-phenyl)-propenone and 4- hydroxy-phenyl guanidine nitrate. Yellow solid (30 %). Anal. RP-HPLC: tK = 9.5 min (10 - 70 % MeCN, purity > 95 %). 'H-NMR (DMS(W6): 55.51 (s, 2H, CH2), 6.42 (d, 2H, J = 8.5 Hz, Ph-H), 7.26 (d, 1H,J= 5.0 Hz, pyrimidine-H), 7.43 (d, IH, J= 7.0 Hz, Ph-H), 7.52 (m, 3H, Ph-H), 8.00 (s, IH, triazole-H), 8.04 (m, 2H, Ph-H), 8.46 (d, IH, J = 5.0 Hz, pyrimidine-H), 8.71 (s, IH, triazole-H). 9.35 (br. s, IH, NH). 13C-NMR (DMSQ-d6): 8 48.50, 53.50, 107.80, 115.70, 121.70, 121.80, 126.90, 127.10, 127.20, 129.90, 130.90, 130.95, 132.60, 137.60, 137.90, 145.00, 152.50, 153.00, 160.95. MS (ESf) m/z 345.4 [M+Hf, Ci9Hi6K6O requires 344.37. 3-[4-(3-[l, 2,4] Triazol-l-ylmethyl-phenyl)-pyrimidin-2-ylamino] -phenol (34) By treatment of 3-dmiemylarnino-l-(3-[l,2,4]triazol-l-yhiiethyl-phenyl)-propenone and 3- hydroxy-phenyl guanidine nitrate. Yellow solid (32 %). Anal. RP-HPLC: iR= 10.8 min (10 - 70 % MeCN, purity > 95 %). 'H-NMR (DMSO-d6): 55.51 (s, 2H, CH2), 6.38 (d, IH, J= 8.0 Hz, Ph-H), 7.07 (t, IH, J= 8.0 Hz, Ph-H), 7.24 (d, IH, /= 8.0 Hz, Ph-H), 7.31 (s, IH, Ph-H), 7.34 (d, IH, J= 5.0 Hz, pyrimidine-H), 7.43 (d, IH, J= 7.5 Hz, Ph-H), 7.53 (t, 2H, /= 7.5, 8.0 Hz, Ph-H), 8.00 (s, IH, triazole-H), 8.09 (m, IH, Ph-H), 8.53 (d, IH, J= 5.0 Hz, pyrimidine-H), 8.72 (s, IH, triazole-H), 9.55 (br. s, IH, NH). 13C-NMR (DMSO-J6): 5 49.30, 52.70, 106.70, 108.60, 109.40, 110.60, 127.10, 129.80, 129.90, 131.00, 137.60, 137.80, 142.20, 145.00, 152.50, 158.20, 159.71, 160.90, 163.90. MS (ESI4) m/z 345,3 [M+Hf, Ci9Hi6N6O requires 344.37. (3-Metho^-pheiiyl)-[4-(3-[l,2,4]triazol-l-ylmethyl-phenyl)-pyrimidin-2-yl]-amme(3S) By treatment of 3-dimethylamino-l-(3-[l,2,4]triazol-l-ylmethyl-phenyl)-propenone and 3- methoxy-phenyl guanidine nitrate. Yellow solid (47 %). Anal. RP-HPLC: t*= 14.5 min (10 - 70 % MeCN, purity > 95 %), 1H-NMR (DMSO-d6): S3.75 (s, 3H, CH3), 5.51 (s, 2H, CH2), 6.54 (d, 1H, /= 8.0 Hz, Ph-H), 7.20 (t, 1H, J= 7.5, 8.0 Hz, Ph-H), 7.32 (m, 2H, pyrimidine-H and Ph-H), 7.44 (d, 1H, /= 8.0 Hz, Ph-H), 7.53 (m, 2H, Ph-H), 7.99 (s, 1H, triazole-H), 8.08 (m, 2H, Ph-H), 8.56 (d, 1H, J = 5.5 Hz, pyrimidine-H), 8.71 (s, 1H, triazole-H), 9.67 (br. s, 1H, NH). 13C-NMR (DMSO-rf6): 552.70, 55.60, 105.30, 107.50, 108.80, 109.90, 111.90, 127.10, 127.20, 129.90, 131.10, 137.70, 137.80, 142.40, 145.00, 152.50,159.80,160.20,160.80,163.80. MS (ESf) m/z 359.4 [M+H]+, C2oHi8N6O requires 358.40. 3-[4-(3-[l,2,4]Triazol-l-ylmethyl-phenyl)-pyrimidin-2-ylaminoJ-benzonitrile(36) By treatment of 3-ditnethylamino-l-(3-[l,2,4]triazol-l-ylmethyl-phenyl)-propenone and N- (3-cyano-phenyl)-guanidtne nitrate. Yellow solid (47 %). Anal. RP-HPLC: t# = 15.6 min (10-70 % MeCN, purity > 95 %). JH-NMR (DMSCW6): £5.52 (s, 2H, CH2), 7.39 (d, 1H, /= 7.5 Hz, Ph-H), 7.46 (m, 2H, pyrimidine-H and Ph-H), 7.54 (m, 2H, Ph-H), 8.01 (s, 1H, triazole-H), 8.09 (m, 3H, Ph-H), 8.31 (s, 1H, Ph-H), 8.63 (d, 1H, /= 5.0 Hz, pyrimidine- H), 8.73 (s, 1H, triazole-H), 10.09 (br. s, 1H, NH). 13C-NMR (DMSO-4): 552.70, 109.70, 112.10, 119.80, 121.90, 123.80, 125.30, 127.20, 130.10, 130.70, 131.20, 137.50, 137.70, 142.10, 145.00, 452.50, 159.00, 159.90, 160.40, 164.10. MS (ESf) m/z 354.3 [M+H]+, C2oHi5N7 requires 353.38. Example 7 [4-(4-Chloro-3-[l,2,4Jtriazol--]-ylmethyl-phenyl)-pyrimidin-2-ylJ-(3-nitro-phenyl)-amine (47) By treatment of 3-dimethylamino-l-(4-chloro-3-[l,2,4]triazol-l-yl-rnethyl-phenyl)- propenone with 3-nitro-phenyl guanidine nitrate. Yellow solid. Anal. RP-HPLC: t# = 19.9 min (10 - 70 % MeCN, purity 95 %). ^-NMR (DMSO-4) 8: 5.61 (s , 2H, CH2), 7.50 (d, 1H, J= 5.0 Hz, pyrimidinyl-H), 7.61 (t, 1H, J= 8.5 Hz, Ph-H), 7.70 (d, 1H, /= 8.5 Hz, Ph- H), 7.83 (d, 1H, /= 8.5Hz, Ph-H), 7.97 (s, 1H, Ph-H), 8.07 (d, /= 8.5Hz, Ph-H), 8.19 (m, 2H, Ph-H and NH), 8.67 (d, 1H, J= S.OHz, pyrimidinyl-H), 8.70 (s, 1H, Ar-H), 9.01 (Is, 53 IH, Ar-H), 10.31 (sbr, IH, NH). MS (ESI*) m/z 408.12 [M+H]+, Ci9H14ClN702 requires 407.81. Example 8 (6-Metho^-pyndm-3-yl)-f4-f3-(4-methyl-piperazin-l-ylmethyl)-phenylJ-pyrimidin-2-yl}' canine (58) By treatment of 3-dimethylamino-l-(3-(4-methyl-piperazinyl-l-yl-methyl-phenyl)- propenone with 6-methoxy-pyridin-3-yl guanidine nitrate. Orange solid. Anal. RP-HPLC: tx = 8.9 min (10 - 70 % MeCN, purity 100 %). 'H-NMR (CD3OD) & 2.91 (s, 3H, CH3), 3.07 (m, 4H, CH2x2), 3.41 (m, 4H, CH2), 3.99 (s, 3H, OCH3), 4.02 (s, 2H, CH2), 7.05 (d, IH, ,7= 8.0 Hz, Ph-H), 7.41 (d, IH, J= 5.0 Hz, pyrimidinyl-H), 7.59 (m, 2H, Ph-H and Ar- H), 8.15 (m, 2H, Ph-H and Ar-H), 8.20 (s, IH, Ph-H), 8.48 (d, IH, J= 5.0Hz, pyranidinyl- H), 8.73 (s, IH, Ar-H). MS (ESf) m/z 391.25 [M+H]+, C22H26N6O2 requires 390.48. Example 9 [4-(3-ImidazoI-l-ylmethyl-phenyl)-pyrimidin-2-yl]-(6-methoxy-pyridin-3-yl)-amine(59) By treatment of 3-dimethylamino-l-(3-(imidazol-l-yl-methyl-phenyl)-propenone with 6- methoxy-pyridin-3-yl guanidine nitrate. Yellow solid. Anal. RP-HPLC: to = 9.8 min (10 - 70 % MeCN, purity 100 %). 'H-NMR (CD3OD) d: 3.97 (s, 3H, OCH3), 5.57 (s, 2H, CH2), 6.92 (d, IH, /= 8.5 Hz, Ph-H), 7.36 (d, IH, /= 5.5 Hz, pyrimidinyl-H), 7.59 (m, 3H, Ph-H and Ar-H), 7.69 (s, IH, Ar-H), 8.05 (m, IH, Ph-H), 8.19 (m, 2H, Ph-H and Ar-H), 8.48 (d, IH, /= 5.5Hz, pyrimidinyl-H), 8.64 (m, IH, Ar-H), 9.10 (s, IH, Ar-H). MS (ESf) m/z 359.06 [M+H]+, C2oH18N60 requires 358.40. Example 10 [4-(3-Dimethyla?n inomethyl-phenyl)-pyrimidin-2-yl]-(3-nitt'o-phenyl)-amine (71) » By treatment of 3-dimethylamino-l-(3-JVVV-dimethylamino-methyl-phenyl)-propenone with 3-nitro-phenyl guanidine nitrate. Yellow solid. Anal. RP-HPLC: tj?= 13.5 min (10 - 70 % MeCN, purity 100 %). 'H-NMR (CD3OD) & 2.94 (s, 6H, CH3), 4.49 (s , 2H, CH2), 7.50 (d, IH, J= 5.5 Hz, pyrimidinyl-H), 7.53 (t, IH, J= 8.5 Hz, Ph-H), 7.70 (d, 2H, Ph-H), 7.74 (d, 1H3 J= 8.5Hz, Ph-H), 7.88 (IH, d, J= 8.5Hz, Ph-H), 8.32 (s, IH, Ph-H), 8.61 (m, 2H, Ph-H and pyrimidinyl-H), 9.60 (s, IH, Ph-H), 10.31 (sbr, IH, NH). MS (ESf) m/z 350.43 [M+Hf, QsHipNsCh requires 349.39. Example 11 3-f4-(4-Methoxy-phenyl)-pyrimidin-2-ylaminoJ-phenol(76) By treatment of 3-dirnethylamino-l-(4-methoxyphenyl)-propenone with 3-hydroxy-phenyl guanidine nitrate. Brown solid. Anal. RP-HPLC: tj? = 13.9 min (10 - 70 % MeCN, purity 100 %). 'H-NMR (CDC13) & 3.89 (s, SH, CH3), 6.55 (m, d, j= s.s HZ, ph-H), 7.01 (m, 2H, Ph-H), 7.1 1 (d, IH, 7= 5.5 Hz, pyrimidinyl-H), 7.13 (s, IH, Ph-H), 7.21 (t, IH, J= 8.5 Hz, Ph-H), 7.40 (sbr, IH, OH), 7.46 (m, IH, Ph-H), 8.05 (d, 2H, J= 8.5Hz, Ph-H), 8.39 (IH, d, /= 5.5Hz, pyrimidinyl-H). MS (ESI4) m/z 294.41 [M+Hf, CiyH^NaOa requires 293.32. Example 12 (l-{3-[2-(3-Mtro-phenylamino)-pyrimidin-4-ylJ-ben2yl}~piperidin~2-yl)-methanol(79) By treatment of 3-dimemylarnmo-l-[3-(2-hydroxymethyl-piperidin-l-ylmethyl)-phenyl]- propenone with 3-nitro-phenyl guanidine nitrate. Yellow solid. Anal. RP-HPLC: t«= 13.9 min (10 - 70 % MeCN, purity 100 %). 'H-NMR (CDC13) S: 1.42 (m, 2H, CH2), 1.60 (m, IH, CH2), 1.73 (m, 3H, CH2), 2.28 (m, IH, CH2), 2.60 (m, IH, CH2), 2.94 (m, IH, CH2), 3.52 (m, IH, CH2), 3.61 (dd, IH, J= 4.5 Hz, CH2), 3.90 (dd, IH, /= 4.5 Hz, CH2), 4.23 (d, IH, J= 13.0 Hz, CH2), 7.29 (d, IH, J = 5.0 Hz, pyrimidinyl-H), 7.47-7.55 (m, 4H, Ph-H), 7.67 (s, IH, Ph-H), 7.74 (d, IH, J= 8.5 Hz, Ph-H), 7.89 (IH, d, J= 8.0 Hz, Ph-H), 7.99 (m, IH, Ph-H), 8.14 (s, IH, Ph-H), 8.52 (d, IH, J= S.OHz, pyrimidnyl-H), 9.13 (sbr, IH, NH). 13C-NMR (DMSO-cfe) & 23.60, 25.50, 27.46, 28.93, 52.18, 58.29, 63.35, 109.79, 113.07, 116.27, 125.31, 126.22, 127.93, 129.47, 130.43, 132.24, 136.86, 141.26, 142.66, 148.86, 159.96, 160.44, 164.53. MS (ESI") m/z 420.47 [M+HJ+, C^H^Os requires 419.48. Example 13 3- [4-(3-Dimethylaminomethyl-phenyl)-pyrimidin-2-ylamino] '-phenol X80) By treatment of 3-dimethylarnrno-l-(3-dimethylaminomethyl-phenyl)-propenone e with 3- hydroxyphenyl guanidine nitrate. Brown solid. Anal. RP-HPLC: t* = 8.9 min (10 - 70 % MeCN, purity 95 %). 'H-NMR (CD3OD) & 2.37 (s, 6H, CH3x2), 3.63 (s, 2H, CH2), 6.55 (dd, J = 2.0, 8.0 Hz, Ph-H), 6.73 (m, IH, Ph-H), 7.16 (m, 2H, pyrimidinyl-H and Ph-H), 7.36 (s, IH, Ph-H), 7.43 (t, IH, 7= 7.5 Hz, Ph-H), 7.87 (d, 2H, J= 7.0 Hz, Ph-H), 8.06 (s, IH, OH), 8.42 (d, IH, J= 4.5Hz, pyrimidinyl-H), 8.45 (s, IH, Ph-H). MS (ESI*) m/z 321.51 [M+H]+, Ci9H2QN4O requires 320.39. Example 14 4- [4-(3-Dimethylaminomethyl-phenyl)-pyrimidin-2-ylamino]'-phenol (81) By treatment of 3-dimemylarnino-l-(3-dimethylaminomethyl-phenyl)-propenone with 4- hydroxyphenyl guanidine nitrate. Brown solid. Anal. RP-HPLC: iR - 7.6 min (10 - 70 % MeCN, purity 100 %). !H-NMR (CD3OD) & 2.36 (s, 6H, CH3x2), 3.62 (s, 2H, CH2), 6.81 (dd, J= 9.0 Hz, Ph-H), 6.97 (m, IH, Ph-H), 7.11 (d, IH, /= 5.5Hz, pyrimidinyl-H), 7.47 (m, 2H, Ph-H), 7.96 (sbr, IH, OH), 8.06 (s, IH, Ph-H), 8.40 (d, IH, J = 5.5Hz, pyrimidinyl-H). MS (ESf) m/z 321.51 [M+H]+, Ci9H2oN4O requires 320.39. Example 15 [4~(3-Dimethylaminomet]iyl-phenyl)-pyrimidin-2-yl]-(4-mojpholin-4-yl-phenyl)-amme (82) By treatment of 3-drmethylamino-l-(3-dmiethylarrnnomethyl-phenyl)-propenone with 4- morpholino-phenyl guanidine nitrate. Yellow solid. Anal. RP-HPLC: t*= 8.3 min (10-70 % MeCN, purity 98 %). 1H-NMR (CD3OD) & 2.31 (s, 6H, CH3x2), 3.14 (m, 4H, CH2), 3.55 (s, 2H, CH2), 3.89 (m, 4H, CH2), 6.95 (d, 2H, J= 9.0 Hz, Ph-H), 7.14 (m, 2H, pyrimidinyl-H and Ph-H), 7.45 (d, 2H, / = 4.5Hz, Ph-H),v7.59 (d, 2H, /= 9.0Hz, Ph-H), 7.97 (sbr, IH, OH), 8.01 (s, IH, Ph-H), 8.43 (d, IH, J= 5.0 Hz, pyrimidinyl-H). MS (ESI1) m/z 390.55 [M+H]+, C23H27N5O requires 389^49. Example 16 [4-(3-Dimethylammomethyl-phenyl)-pyrimidin-2-yl]-(6-methoxy-pyridin-3-yl)-amine(Siy) By treatment of 3-dimemylamino-l-(3-dimethylaminomethyl-phenyl)-propenone with 6- methoxy-pyridin-3-yl guanidine nitrate. Yellow solid. Anal. RP-HPLC: \R= 9.8 min (10- 56 70 % MeCN, purity 100 %). 'H-NMR (CD3OD) & 2.30 (s, 6H, CH3), 3.54 (s, 2H, CH2), 3.95 (s, 3H, OCH3), 6.78 (d, 1H, 7= 9.5 Hz, Ph-H), 7.18 (d, 1H, J= 5.5 Hz, pyrimidinyl- H), 7.21 (s, 1H, Ph-H/Ar-H), 7.45 (m, 1H, Ar-H), 7.96 (m, 1H, Ar-H), 8.00 (m, 1H, Ph-H), 8.04 (dd, 1H, J = 2.5, 8.5 Hz, Ph-H), 8.35 (d, 1H, J= 2.5Hz, Ar-H), 8.43 (d, 1H, /= 5.5Hz, pyrimidinyl-H). MS (ESI+) m/z 336.51 [M+Hf, Ci9H2iN5Orequires 335.40. Example 17 [4-(3-Diethylaminomethyl-phenyl)-pyrimidin-2-yl]-(3-nitro-phenyl)-amine(84) By treatment of l-(3-diethylaminomethyl-phenyl)-3-dimethylamino-propenone with 3- nitro-phenyl guanidine nitrate. Yellow solid. Anal. RP-HPLC: i* = 14.0 min (10 - 70 % MeCN, purity 100 %). 'H-NMR (DMSO-^D & 1.02 (t, J= 6.5 Hz, 6H, CH3), 2.59 (m, 4H, CH2), 3.73 (s, 2H, CH2), 7.53-7.60 (m, 2H, Ph-H and pyrimidinyl-H), 7.81 (m, 1H, J= 8.5 Hz, Ph-H), 7.70 (d, 2H, Ph-H), 7.74 (d, 1H, J= 8.5Hz, Ph-H), 7.88 (m, 1H, Ph-H), 8.09 (m, 1H, Ph-H), 8.20 (s, 1H, Ph-H), 8.65 (d, 1H, J= 5.0 Hz, pyrimidinyl-H), 9.16 (m, 1H, Ph-H), 10.26 (sbr, 1H, NH). 13C-NMR (DMSO-J6) & 12.03, 31.39, 46.85, 57.35, 109.74, 113.09, 116.33, 125.34, 126.41, 127.97, 129.56, 130.45, 132.27, 136.93, 142.66, 148.86, 160.06,160.44,164.41. MS (ESf) m/z 378.40 [M+H]+, C2iH23N5O2 requires 377.44. Example 18 Methyl-3-nitro-^-{3-[2-(3-nitro-phenylamino)-pynmidin-4-yl]-benzyl}-benzenesulfonamide (85) By treatment of ^-[3-(3-dimemylamino-acryloyl)-benzyl]-I-methyl-3-nitro-benzenesulfonamide with 3-nitro-phenyl guanidine nitrate. Yellow solid. Anal. RP-HPLC: t^ = 23.5 min (10 - 70 % MeCN, purity 90 %). 'H-NMR (DMSO-d6) & 2.75 (s, 3H, CH3), 4.42 (s, 2H, CH2), 7.31 (d, 1H, /= S.OHz, pyrimidinyl-H), 7.49 (t, 1H, /= 8.5 Hz, Ph-H), 7.53- 7.62 (m, 3H, Ph-H), 7.83(d, 1H, J= 7.5 Hz, Ph-H), 7.88 (d, 1H, J = 8.0 Hz, Ph-H), 8.00 (d, 1H, J= 7.5 Hz, Ph-H), 8.21 (d, 1H, J= 7.5 Hz, Ph-H), 8.25 (s, 1H, Ph-H), 8.50 (d, 1H, J= 8.0 Hz, Ph-H), 8.54 (d, 1H, J= 5.0 Hz, pyrimidinyl-H), 8.70 (m, 1H, Ph-H), 9.29 (s, 1H, Ph-H). MS (ESf) m/z 52/33 [M+H]+, C24H2oN6O6S requires 520.52. Example 19 (3-Nitro-phenyl)-{4-[3-(2-phenylaminomethyl-pynolidin-l-ylmethyl)-phenyl]-pyrimidin-2- yl}-amine (86) By treatment of 3-dimethylamino-l-[3-(2-phenylaminomethyl-pyrrolidin-l-ylinethyl)- phenylj-propenone with 3-nitro-phenyl guanidine nitrate. Yellow solid. Anal. RP-HPLC: \.R = 17.8 min (10 - 70 % MeCN, purity 93 %). 'H-NMR (CDC13) & 1.29 (m, 1H, CH2), 1.75 (m, 2H, CH2), 1.84 (m, 1H, CH2), 1.99 (m, 1H, CH2), 2.33 (m, 1H, CH2), 2.91 (m, 1H, CH2), 3.04 (m, 1H, CH2), 3.22 (m, 1H, CH2), 3.47 (m, 1H, CH2), 4.08 (m, 1H, CH2), 6.60 (d, 2H, /= 8.0 Hz, Ph-H), 6.67 (d, 1H, J= 7.0 Hz, Ph-H), 7.13 (t, 2H, J = 8.5 Hz, Ph-H), 7.25 (d, 1H, J = 5.5 Hz, pyrimidinyl-H), 7.45-7.52 (m, 4H, Ph-H), 7.74 (m, 1H, Ph-H), 7.88 (d, 1H, /= 8.5 Hz, Ph-H), 7.99 (1H, d, J= 9.0 Hz, Ph-H), 8.11 (s, 1H, Ph-H), 8.52 (d, 1H, J = 5.5 Hz, pyrimidnyl-H), 9.12 (s, 1H, Ph-H). MS (ESf) m/z 482.50 [M+H]+, C28H28N6O2 requires 480.56. Example 20 l-{3-[2-(3-Nitro-phenylamino)-pyrimidin-4-yl]-benzyl}-piperidine-3-carboxylicacid amide (99) By treatment of l-[3-(3-dimethylamino-acryloyl)-benzyl]-piperidine-3-carboxylic acid amide with 3-nitro-phenyl guanidine nitrate. Yellow solid. Anal. RP-HPLC: t^= 17.8 min (10 - 70 % MeCN, purity 87 %). MS (ESI1) m/z 433.48 [M+H]+, C^H^NeOs requires 432.48. Example 21 X. 2-(l-{3-f2-(3-Nitro-phenylammo)-pyrimidin-4-yl]-benzyl}-piperidin-3-yl)-ethanol(100) By treatment of 3-dimethylarnino-l-{3-[3-(2-hydroxy-ethyl)-piperidin-l-yhnethyl]- phenylj-propenone with 3-nitro-phenyl guanidine nitrate. Brown solid. Anal. RP-HPLC: fyj = 14.3 min (10 - 70 % MeCN, purity 99 %). !H-NMR (CDC13) & 1.40 (m, 1H, CH2), 1.48 (m, 2H, CH2), 1.56 (m, 1H, CH2), 1.72 (m, 2H, CH2), 1.81 (m, 1H, CH2), 2.14 (m, 1H, CH2), 2.23 (m, 1H, CH2), 2.60 (m, 1H, CH2), 2.85 (m, 1H, CH2), 3.33 (m, 1H, CH2), 3.52 (d, 1H, /= 13.5 Hz, CH2), 3.66 (m, 1H, CH2), 4.14 (d, 1H, /= 13.5 Hz, CH2), 7.38 (d, 1H, 58 J= 5.5 Hz, pyrimidinyl-H), 7.49 (m, 3H, Ph-H), 7.81 (d, 1H, J= 8.5 Hz, Ph-H), 7.87(m, 1H, J= 8.5 Hz, Ph-H), 8.08 (m, 1H, J= 8.0 Hz, Ph-H), 8.21 (m, 1H, Ph-H), 8.51 (d, 1H, J = 5.0 Hz, pyrimidinyl-H), 9.22 (s, 1H, Ph-H). MS (ESf) m/z 434.26 [M+Hf, C24H27N5O3 requires 433.50. Example 22 (l-{3-[2-(4-Morpholin-4-yl-phenylamino)-pyrimidin-4-yl]-benz)>l}-piperidin-2-yl)- methanol (101) By treatment of 3-dimethylamino-l-[3-(2-hydroxymethyl-piperidin-l-yhnethyl)-phenyl]- propenone with 3-nitro-phenyl guanidine nitrate. Brown solid. Anal. RP-HPLC: iR = 9.02 min (10 - 70 % MeCN, purity 87 %). !H-NMR (CD3OD) 5: 1.35 (m, 1H, CH2), 1.47-1.59 (m, 3H, CH2), 1.72-1.81 (m, 2H, CH2), 2.14 (m, 1H, CH2), 2.41 (m, 1H, CH2), 2.84 (m, 1H, CH2), 3.11 (m, 5H, CH2), 3.44 (d, 1H, J= 13.5 Hz, CH2), 3.73 (m, 1H, CH2), 3.84 (m, 4H, CH2), 4.25 (d, 1H, /= 13.5 Hz, CH2), 6.99 (dd, 2H, /= 2.0, 7.0 Hz, Ph-H), 7.24 (d, 1H, /= 5.0 Hz, pyrimidinyl-H), 7.44-7.50 (m, 2H, Ph-H), 7.62 (dd, 1H, J= 2.0, 6.5 Hz, Ph-H), 8.01 (d, 1H, J = 5.5 Hz, Ph-H), 8.16 (s, 1H, Ph-H), 8.38 (d, 1H, / = 5.0 Hz, pyrimidinyl-H). MS (ESf) m/z 460.43 [M+Hf, C27H33N5O2 requires 459.58. Example 23 (l-{3-[2-(6-Methoxy-pyridin-3-ylamino)-pyrimidin-4-yl]-benzyl}-piperidin-2-yl)-methanol (102) By treatment of 3-dirnethylamino-l-[3-(2-hydroxymethyl-piperidin-l-ylmethyl)-phenyl]- propenone with Ar-(6-methoxy-pyridin-3-yl)-guanidine nitrate. Brown solid. Anal. RPHPLC: tR= 10.1 min (10 - 70 % MeCN, purity 95 %). JH-NMR (CD3OD) & 1.36 (m, 1H, CH2), 1.52 (m, 3H, CH2), 1.78 (m, 2H, CH2), 2.14 (m, 1H, CH2), 2.42 (m, 1H, CH2), 2.84 (m, 1H, CH2), 3.45 (d, 1H, /= 13 Hz, CH2), 3.73 (dd, 1H, CH2), 3.84 (m, 1H, CH2), 3.89 (s, 3H, CH3), 4.24 (d, 1H J= 13.5 Hz, CH2), 6.82 (d, 1H, J= 9.5 Hz, Ph-H), 7.30 (d, 1H, J = 5.5 Hz, pyrimidinyl-H), 7.45-7.51 (m, 2H, Ar-H and Ph-H), 8.12 (d, 1H, J= 9.5 Hz, Ph- H), 8.06 (d, 1H, J= 3.0 Hz, Ph-H), 8.07 (d, 1H, J= 3.0 Hz, Ar-H), 8.15 (s, 1H, Ph-H), 8.43 (d, 1H, y= 5.0 Hz, Ph-H), 8.53 (d, 1H, J= 3.0 Hz, Ar-H). MS (ESI4) m/z 406.34 [M+H]+, requires 405.49. Example 24 3-{4'[3-(2-Hydroxymethyl-piperidin-l-ylmethyl)-phenyl]-pynmidin-2-ylamino}-phenol (103) By treatment of 3-dimethylamino-l-[3-(2-hydroxymethyl-piperidin-l-ylmethyl)-phenyl]- propenone with 3-hydroxyphenyl-guanidine nitrate. Brown solid. Anal. RP-HPLC: to = 9.8 min (10-70 % MeCN, purity 100 %). *H-NMR (CD3OD) & 1.38 (m, 1H, CH2), 1.45-1.59 (m, 3H, CH2), 1.72-1.82 (m, 2H, CH2), 2.15 (m, 1H, CH2), 2.43 (m, 1H, CH2), 2.88 (m, 1H, CH2), 3.45 (d, 1H, /= 13 Hz, CH2), 3.74 (m, 1H, CH2), 3.85 (m, 1H, CH2), 4.27 (d, 1H J= 13.5 Hz, CH2), 6.46 (m, 1H, Ph-H), 7.12 (m, 3H, Ph-H), 7.30 (d, 1H, J= 5.0 Hz, pyrimidinyl-H), 7.46 (s, 1H, Ph-H), 7.50 (m, 1H, Ph-H), 8.06 (d, 1H, /= 7.5 Hz, Ph-H), 8.20 (s, 1H, Ph-H), 8.43 (d, 1H, J = 5.5 Hz, pyrimidinyl-H). MS (ESI4) m/z 391.42 [M+H]+, C23H26N4O2 requires 390.48. Example 25 (3-Methanesulfonyl-phenyl)-[4-(3-[l,2,4]triazol-l-ylmethyl-phenyl)-pyrimidin-2-yl]-amine (104) Brown soUd. Anal. RP-HPLC: t*= 13.2 min (10 - 70 % MeCN, purity 89 %). !H-NMR (CDC13) & 3.07 (s, 3H, CH3), 7.22 (d, 1H, J = 5.5 Hz, pyrimidinyl-H), 7.47-7.51 (m, 3H, Ph-H), 7.93 (m, 2H, Ph-H and Ar-H), 8.32 (s, 1H, Ph-H), 8.33 (s, 1H, Ar-H), 8.45 (d, 1H, J = 5.5 Hz, pyrimidinyl-H), 9.10 (s, 1H, Ar-H). MS (ESf) m/z 407.31 [M+H]+,C2oHi8N602S requires 406.46. Example 26 (l-{3-[2-(3-Nitro-phenylamino)-pyrimidin-4-yl]-benzyl}-piperidin-3-yl)-methanol(\Q5) Yellow solid. Anal. RP-HPLC: fo= 12.9 min (10 - 70 % MeCN, purity > 95 %). 'H-NMR (CD3OD) & 0.97 (m, 1H, CH2), 1.61 (m, 1H, CH2), 1.68-1.82 (m, 4H, CH2), 2.05 (m, 1H, CH2), 2.90 (d, 1H, /= 12.5 Hz, CH2), 3.04 (d, 1H, J= 7.5 Hz, CH2), 3.31 3.42 (m, 1H, 60 CH2), 3.67 (m, 2H, CH2), 7.39 (d, 1H, J= 5.5 Hz, pyrimidinyl-H), 7.49 (m, 3H, Ph-H), 7.84 (m, 2H, Ph-H), 8.09 (m, 1H, Ph-H), 8.23 (s, 1H, Ph-H), 8.51 (d, 1H, J= 4.5 Hz, pyrimidinyl-H), 9.26 (d, 1H, Ph-H). MS (ESI") m/z 420.15 [M+Hf, C23H25NsO3 requires 419.48. Example 27 4-{4-[3-(2-Hydroxymethyl-piperidin-l-ylmethyl)-phenyl]-pynmidin-2-ylamino}-phenol (106) Brown solid. Anal. RP-HPLC: tR = 8.5 min (10 - 70 % MeCN, purity 100 %). 'H-NMR (CD3OD) S: 1.40 (m, 1H, CH2), 1.50-1.62 (m, 3H, CH2), 1.75-1.83 (m, 2H, CH2), 2.24 (m, 1H, CH2), 2.53 (m, 1H, CH2), 2.90 (m, 1H, CH2), 3.54 (d, 1H, J= 13.0 Hz, CH2), 3.82 (m, 2H, CH2), 4.30 (d, 1H J= 13.5 Hz, CH2)5 6.78 (d, 2H, J= 9.0 Hz, Ph-H), 7.23 (d, 1H, J= 5.5 Hz, pyrimidinyl-H), 7.46-7.53 (m, 4H, Ph-H), 8.04 (d, 1H, /= 9.0 Hz, Ph-H), 8.15 (s, 1H, Ph-H), 8.37 (d, 1H, J = 5.5 Hz, pyrimidinyl-H). MS (ESI^) m/z 391.25 [M+H]+, C23H26N4O2 requires 390.48. Example 28 (l-{3-[2-(3t5-Bis-hydroyymethyl-phenylamino)-pyrimidin~4-yl]-benzyl}-piperidin-2-yl)- methanol (107) Brown solid. Anal. RP-HPLC: t* = 8.3 min (10 - 70 % MeCN, purity 90 %). 'H-NMR (CD3OD) S: 1.40 (m, 1H, CH2), 1.50-1.62 (m, 3H, CH2), 1.75-1.83 (m, 2H, CH2), 2.24 (m, 1H, CH2), 2.54 (m, 1H, CH2), 2.90 (m, 1HS CH2), 3.57 (d, 1H, J= 13.0 Hz, CH2), 3.80 (m, 2H, CH2), 4.33 (d, 1H J= 13.5 Hz, CH2), 7.02 (s, 1H, Ph-H), 7.32 (d, 1H3 /= 5.5 Hz, pyrimidinyl-H), 7.48-7.56 (m, 4H, Ph-H), 7.76 (s, 2H, OH), 8.11 (d, 1H, J= 8.0 Hz, Ph- H), 8.23 (s, 1H, Ph-H), 8.46 (d, 1H,/= 5.0 Hz, pyrimidinyl-H). MS (ESf) m/z 435.39 [M-fHf, C25H3oN4O3 requires 434.53. Example 29 (l-{3-f2-(4-Methyl-3-nitro~phenylamino)-pyrimidin-4--ylJ-benzyl}-piperidin-2-yl)-methanol (108) Yellow solid. Anal. RP-HPLC: t*= 15.2 min (10 - 70 % MeCN, purity 100 %). 'H-NMR (CDCls) & 1.42 (m, 2H, CH2), 1.61 (m, IH, CH2), 1.74 (m, 3H, CH2), 2.26 (m, IH, CH2), 2.59 (s, 3H, CH3), 2.60 (m, IH, CH2), 2.92 (m, IH, CH2), 3.53 (d, IH, /= 13.0 Hz, CH2), 3.60 (dd, IH, /= 4.0,11.0 Hz, CH2), 3.91 (dd, IH, /= 4.5,11.0 Hz, CH2), 4.24 (d, IH, J= 13.5 Hz, CH2), 7.26 (d, IH, J= 5.0 Hz, pyrimidinyl-H), 7.28 (d, IH, J= 8.5 Hz, Ph-H), 7.47-7.53 (m, 3H, Ph-H), 7.57 (dd, IH, /= 2.5, 8.5 Hz, Ph-H), 8.65 (s, IH, Ph-H), 8.97 (d, IH, J = 7.5 Hz, Ph-H), 8.11 (s, IH, Ph-H), 8.49 (d, IH, J = 5.0 Hz, pyrimidinyl-H), 8.87 (m, IH, OH). MS (ESI4) m/z 434.51 [M+H]+, C24H27N5O3 requires 433.50. Example 30 3-[4-(4-Ethoxy-phenyl)-pyrimidin-2-ylamino]-phenol (W9) By treatment of 3-Dimethylamino-l-(4-ethoxy-phenyl)-propenone with 3-hydroxyl-phenyl guanidine nitrate. Brown solid. Anal. RP-HPLC: t* = 15.5 min (10 - 70 % MeCN, purity 100 %). 'H-NMR (CDci3) & 1.44 (t, SH, y=7.5 HZ, CH3), 4.os (q, 2H, j= 7.0 HZ, cn2), 6.54 (dd, IH, J = 2.0, 7.0 Hz, Ph-H), 6.98 (m, 2H, Ph-H), 7.07 (d, IH, / = 5.5 Hz, pyrimidinyl-H), 7.10 (s, IH, OH), 7.18 (t, IH, /= 8.5 Hz, Ph-H), 7.32 (s, IH, Ph-H), 7.42 (m, IH, Ph-H), 8.01 (d, 2H, J = 8.5Hz, Ph-H), 8.38 (IH, d, J= 5.0 Hz, pyrimidinyl-H). MS (ESI") m/z 308.40 [M+H]+, C18Hi7N3O2 requires 307.35. Example 31 4-[4- (4-Methoxy-phenyl)-pyrimidin-2-ylamino]-phenol (110) Yellow solid. Anal. RP-HPLC: fc = 12.9 (10 - 70 % MeCN, purity 100 %). 1H-NMR (CDC13) & 3.82 (s, 3H, CH3), 6.79 (m, 2H, Ph-H), 6.95 (m, 2H, Ph-H), 6.99 (m, IH, pyrimidinyl-H), 7.40 (m, 2H, Ph-H), 7.96 (m, 2H, Ph-H), 8.25 (m, IH, pyrimidinyl-H). MS (ESI*) m/z 294.15 [M+H]+, Ci7Hi5N3O2 requires 293.32. Example 32 [4-(4-Methoxy-phenyl)-pyrimidin-2-yl]-(4-morpholin-4-yl-phenyl)-amine (111) Yellow solid. Anal. RP-HPLC: tn« 13.8 min (10 - 70 % MeCN, purity 100 %). ]H-NMR (DMSO-4) * 3.04 (m, 4H, CH2), 3.74 (m, 4H, CH2), 3.83 (s, 3H, CH3), 6.92 (d, 2H, J = 9.0 Hz, Ph-H), 7.08 (d, 2H, /= 8.5 Hz, Ph-H), 7.25 (d, 1H, J = 5.0 Hz, pyriniidinyl-H), 7.66 (d, 2H, J= 9.5 Hz, Ph-H), 8.12 (d, 1H, J = 9.0 Hz, Ph-H), 8.41 (d, 1H, J= 5.5 Hz, pyrimidinyl-H), 9.33 (s, 1H, NH). MS (ESf ) m/z 363.09 [M+H]+, €21^2^02 requires 362.43. Example 33 [4-(4-Methoty-phenyl)-pyj-imidin-2-yl]-(6-methoxy-pyridin-3-yl)~amine(124) Yellow solid. Anal. RP-HPLC: t*= 15.2 min (10 - 70 % MeCN, purity 100 %). 'H-NMR 8\ 3.83 (s, 3H, CH3), 3.84 (s, 3H, CH3), 6.81 (d, 1H, J= 9.0 Hz, Ar-H), 7.09 (d, 2H, J= 9.0 Hz, Ph-H), 7.32 (d, 1H, J= 5.0 Hz, pyrimidinyl-H), 8.06 (dd, 1H, /= 2.5, 9.0 Hz, Ar-H), 8.11 (dd, 2H, J= 2.5, 9.0 Hz, Ph-H), 8.44 (d, 1H, J= 5.5 Hz, pyrimidrnyl- H), 8.56 (d, 1H, J = 2.5 Hz, Ar-H), 9.50 (s, 1H, NH). MS (ESf) m/z 406.34 [M+H]+, requires 308.33. Example 34 {3-[2-(6-Methoxy-pyridin-3-ylamino)-pyrimidin-4-yl]-phenyl}-methanol(\2S) Yellow solid. Anal. RP-HPLC: t*= 11.3 min (10 - 70 % MeCN, purity 100 %). 1H-NMR (DMSO-J6) 8: 3.83 (s, 3H, CH3), 4.59 (d, 2H, J= 6.5 Hz, CH2), 6.81 (d, 1H, J = 9.5 Hz, Ar-H), 7.36 (d, 1H, /= 5.5 Hz, pyrimidinyl-H), 7.49 (m, 2H, Ph-H), 7.99 (m, 1H, Ar-H), 8.10 (m, 2H, Ph-H and Ar-H), 8.51 (d, 1H, J= 5.0 Hz, pyrimidinyl-H), 8.55 (d, 1H, J= 2.5 Hz, Ar-H), 9.59 (s, 1H, NH). MS (ESf) m/z 309.43 [M+H]+, Ci7Hi6N4O2 requires 308.33. Example 35 (3-Nitro-phenyl)-{4-[4-(2-[l,2, 4]triazol-l -yl-ethyl)-phenyl]-pyrimidin-2-yl}-amine (126) Yellow solid. Anal. RP-HPLC: t*= 17.8 min (10 - 70 % MeCN, purity 100 %). 1H-NMR (CDC13) 5: 3.25 (t, 2H, /= 7.0 Hz, CH2), 4.44 (t, 2H, J= 7.0 Hz, CH2), 7.21 (d, 2HS /= 8.5 Hz, Ph-H), 7.22 (d, 1H, J= 5.5 Hz, pyrimidinyl-H), 7.46 (t, 1H, J= 8.0 Hz, Ph-H), 7.74 (d, 1H, J= 8.5 Hz, Ph-H), 7.80 (s, 1H, Ar-H), 7.87 (d, 1H, J = 8.5Hz, Ph-H), 7.95 (m, 2H, Ar- H and Ph-H), 8.04 (d, 2H, J= 8.0 Hz, Ph-H), 8.47 (d, 1H, J= 5.5Hz, pyrimidinyl-H), 9.14 (sbr, 1H, NH). MS (ESf) m/z 388.48 [M+H]+, C2oHnN7O2 requires 387.39. Example 36 (l-{4-[2-(3-Nitro-phenylamino)-pyrimidin-4-yl]-benzyl}-piperidin-2-yl)-methanol(12T) Yellow solid. Anal. RP-HPLC: t* = 13.3 min (10 - 70 % MeCN, purity 96 %). 'H-NMR (CDC13) S: 1.39 (m, 2H, CH2), 1.57 (m, IH, CH2), 1.70 (m, 3H, CH2), 2.18 (m, IH, CH2), 2.50 (m, IH, CH2), 2.89(m, IH, CH2), 3.41 (d, IH, J= 13.5 Hz, CH2), 3.57 (dd, IH, J = 4.0, 11.0 Hz, CH2), 3.88 (dd, IH, J= 4.5, 11.0 Hz, CH2), 4.15 (d, IH, /= 13.0 Hz, CH2), 7.26 (d, IH, /= 5.5 Hz, pyrimidinyl-H), 7.48 (m, 3H, Ph-H), 7.78 (dd, 2H, J= 2.5,7.5 Hz, Ph-H), 7.82 (s, IH, Ph-H), 7.87 (dd, IH, J = 2.5, 7.5 Hz, Ph-H), 8.09 (d, 2H, J= 7.5 Hz, Ph-H), 8.52 (d, IH, /= 5.5 Hz, pyrimidinyl-H), 9.05 (m, IH, OH/NH). !3C-NMR(DMSOrf6) 8: 23.76, 25.72, 29.22, 52.48, 58.41, 63.27, 63.75, 109.44, 113.05, 116.17, 125.26, 127.48, 129.62, 130.37, 135.32, 142.68, 144.47, 148.83, 159.81, 160.41, 164.32. MS (ESf) m/z 420.40 [M+H]+, C23H25N5O3 requires 419.48. Example 37 [4-(4-Methoxy-phenyl)-pyrimidin-2-yl]-(3,4,5-trimethoxy-phenyl)-amine (128) Yellow solid. Anal. RP-HPLC: t* = 15.2 min (10 - 70 % MeCN, purity 94 %). 1H-NMR (DMSO-4) 5: 3.62 (s, 3H, CH3), 3.79 (s, 6H, CH3), 3.84 (s, 3H, CH3), 7.09 (d, 2H, J= 9.0 Hz, Ph-H), 7.30 (s, 2H, Ph-H), 7.34 (d, IH, J = 5.5 Hz, pyrimidinyl-H), 8.16 (d, 2H, J= 9.5 Hz, Ph-H), 8.47 (d, IH, J = 5.0 Hz, pyrimidinyl-H), 9.46 (s, IH, NH). MS (ESI4) m/z 366.47 [M+H]+, C20H2iN3O4 requires 367.40. Example 38 \N'Methyl-N-{3-[2-(3-nitro-phenylamino)-pyrimidin-4-yl]-phenyl}-methanesulfonamide (129) Yellow solid. Anal. RP-HPLC: tR = 17.0 min (10 - 70 % MeCN, purity 100 %). !H-NMR (DMSO-J6) 5: 3.01 (s, 3H, CH3), 3.33 (s, 3H, CH3), 7.58-7.62 (m, 4H, Ph-H and pyrimidinyl-H), 7.83 (dd, IH, /= 2.5, 8.5 Hz, Ph-H), 8.15 (m, 2H, Ph-H), 8.20 (s, IH, Ph- H), 8.68 (d, IH, J= 5.5 Hz, pyrimidinyl-H), 9.03 (m, IH, Ph-H), 10.29 (s, IH, NH). MS (ESf) m/z 400.50 [M+H]+, CisHnNsC^S requires 399.42. Example 39 N-{3-[2-(3-Hydroxy-phenylamino)-pyrijnidin-4~yl]-phenyl}-^-methyl-methanesulfonamide (130) Yellow solid. Anal. RP-HPLC: t* = 12.9 min (10 - 70 % MeCN, purity 92 %). !H-NMR (DMSO-Je) 3: 3.01 (s, 3H, CH3), 3.32 (s, 3H, CH3), 7.38 (m, 1H, Ph-H), 7.06 (t, 1H, J = 8.5 Hz, Ph-H), 7.25 (m, 1H, Ph-H), 7.37 (m, 1H, Ph-H), 7.42 (d, 1H, J = 5.0 Hz, pyrimidinyl-H), 7.59 (m, 1H, Ph-H), 8.09 (m, 1H, Ph-H), 8.19 (s, 1H, Ph-H), 8.56 (d, 1H, J = 5.5 Hz, pyrimidinyl-H), 9.25 (s 1H, Ph-H), 9.59 (s, H, NH). MS (ESI4) m/z 371.41 [M+H]+, Ci8H18N4O3S requires 370.43. Example 40 N-{3-[2-(4-Hydroxy-phenylamino)-pyrimidin-4-ylJ-phenyl}-^-methyl-methanesulfonamide (131) Yellow solid. Anal. RP-HPLC: t* = 11.0 min (10 - 70 % MeCN, purity 93 %). 'H-NMR (CDC13) & 2.86 (s, 3H, CH3), 3.37 (s, 3H, CH3), 6.82 (m, 2H, Ph-H), 7.08 (d, 1H, J= 5.0 Hz, pyrimidinyl-H), 7.44 (m, 2H, Ph-H), 7.49 (m, 2H, Ph-H), 7.88 (m, 1H, Ph-H), 8.13 (s, 1H, Ph-H), 8.38 (d, 1H, J = 5.0 Hz, pyrimidinyl-H). MS (ESf) m/z 371.41 [M+H]+, Ci8HigN4O3S requires 370.43. Example 41 N-{3-[2-(6-Methoxy~pyj-^in-3-ylamino)-pyrimidin-4-yl]-phenyl}-'^-methyl-methanesulfonamide (132) Yellow solid. Anal. RP-HPLC: I* = 12.9 min (10 - 70 % MeCN, purity 94 %). JH-NMR (CDC13) & 2.88 (s, 3H, CH3), 3.38 (s, 3H, CH3), 3.93 (s, 3H, CH3), 6.77 (d, 1H, J= 9.0 Hz, Ph-H), 7.14 (d, 1H, J= 5.5 Hz, pyrimidinyl-H), 7.50 (m, 2H, Ph-H), 7.92 (m, 1H, Ph-H), 7.99 (dd, 1H, J= 2.0, 8.5 Hz, Ph-H), 8.11 (s, 1H, Ph-H), 8.37 (d, 1H, J = 2.5 Hz, Ph-H), 8.44 (d, 1H, / = 5.5 Hz, pyrimidinyl-H). MS (ESf) m/z 386.40 [M+H]+, Cig requires 385.44. Example 42 General conditions for the following examples (43-45) Microwave reactions were performed using a CEM Discover or Explorer System. HPLC separation was achieved using a Biotage ParallexFLEX system with an automated (UV detection) fraction collector using a SUPLELCOSIL CIS reversed phase preparative column, and gradient elution with water (containing 0.05 % CF3COOH) - acetomtrile as solvents. HPLC samples were evaporated in vacuo using a CHRIST Beta-RVC centrifugeevaporator system. Electrospray mass spectrometry was performed using a Micromass Platform II machine. NMR spectra were recorded using a Brucker ARX 250 (MHz) instruments. Example 43 3-[4-(2,5-Dimethyl-phenyl)-pyrimidin-2-ylamino]-phenol (62) A mixture of 2,4-dichloropyrimidine (50 mg, 0.33 mmol), 2,5-dimethylphenylboronic acid (50 mg, 0.33 mmol), caesium carbonate (136 mg, 1.0 mmol), palladium (H) acetate (5 mg, 0.02 mmol), acetomtrile (2 mL) and water (0.2 mL) in a 10-mL microwave tube was sealed and heated in the microwave at 130 °C for 15 min. Upon cooling the organic phase was transferred into another microwave tube, to which was added 3-aminophenol (55 mg, 0.50 mmol) and toluene-4-sulfom'c acid monohydrate (95 mg, 0.50 mmol). The tube was resealed and irradiated at 130 °C in the microwave for 15 min. The reaction mixture was filtered and purified by HPLC to give 58 mg (61 %) of the title compound. 'H-NMR (MeCN-3) & 2.55 (s, 3H, CH3), 2.58 (s, 3H, CH3), 6.78-8.59 (m, 9H, Ar-H), 10.97 (s, 1H, NH). MS (ESf) m/z 292 [M+Hf, Ci8Hi7N3O requires 291.35). Example 44 3-[2-(3-Nitro-phenylamino)-pyrimidin-4-yl]'-phenol(55) To a microwave tube was added 2,4-dichloropyriniidine (0.075 g, 0.50 mmol), 3- hydroxyphenylboronic acid (0.069 g, 0.50 mmol), palladium (n) acetate (0.011 g, 0.05 mmol), caesium carbonate (0.245 g, 0.75 mmol), MeCN (3 mL) and H2O (0.5 mL). The vessel was sealed and irradiated in the microwave at 130 °C for 15 min. On cooling, the reaction mixture (approx. 0.17 mmol) was transferred to another microwave tube. To this a mixture of 3-nitroaniline (0.028 g, 0.2 mmol) and toluene-4-sulfonic acid monohydrate (0.065 g, 0.34 mmol) and MeCN (1 mL) was added. The vessel was sealed and irradiated in the microwave at 130 °C for 15 min. On cooling the reaction mixture was filtered and purified by HPLC to afford 20 mg of the title compound. Yield 38 %; 'H-NMR (CD3OD) & 6.92-9.08 (m, 10H, Ar-H). MS (ESI*) m/z 309 [M+H]+, deK^Os requires 308.29. Example 45 The following compounds were prepared in a similar manner as described in Examples 43 and 44: [3-[2-(3-Hydroxy-phenylamino)-pyrimidin-4-yl] -phenol (S6) Yield 65 %; !H-NMR (CD3OD) & 6.92-8.71 (m, 10H, Ar-H). MS (ESI4) m/z 280 [M+H]+, Ci6Hi3N3O2 requires 279.29. ' 3-[2-(3-Fluoro-phenylamino)-pyrimidin-4-yl] -phenol (57) Yield 61 %; 'H-NMR (CD3OD) & 6.93-8.55 (m, 10H, Ar-H), 10.34 (s, 1H, OH). MS (ESf) m/z 282 [M+H]+, Ci6Hi2FN3O requires 281.28. 3-[4-(3-Nitro-phenyl)-pyrimidin-2-ylamino] '-phenol (64) Yield 53 %; 'H-NMR (CD3OD) & 6.35-8.87 (m, 10H, Ar-H). MS (ESI+j m/z 309 [M+H]+, Ci6Hi2N4O3 requires 308.29. ^-{3-[2-(3-Hydroxy-p1ieiiylamino)-pyrimidin-4-yl]-phenyl}-acetamide{&T) Yield 12 %; 'H-NMR (CD3OD) 8: 2.28 (s, 3H, CH3), 6.33-9.54 (m, 10H, Ar-H). MS (ESf) m/z 321 [M+H]+, CigHieN^ requires 320.35. N-{3-[2-(3-Nitro-phenylamino)-pyrimidin-4-yl]-phenyl}-acetamide(69) Yield 24 %; 1H-NMR (CD3OD) & 2.21 (s, 3H, CH3), 7.47-9.14 (m, 10H, Ar-H). MS (ESI") m/z 350 [M+H]+, Ci8Hi5N5O3 requires 349.34. 3-[2-(3-Hydroxymethyl-phenylamino)-pyrimidin-4-yl)'-phenol (72) Yield 14 %; 'H-NMR (CD3OD) & 2.39 (s, 1H, OH), 4.70 (s, 2H, CH2), 8.40-7.02 (m, 10H, Ar-H). MS (ESI*) m/z 294 [M+HJ+, Ci7Hi5N3O2 requires 293.32. 3-[4-(3-Methoxy-phenyl)-pyrimidin-2-ylamino]-phenol ($$) Yield 23 %; 'H-NMR (CD3OD) 8: 3.93 (s, 3H, CH3), 6.64-8.41 (m, 10H, Ar-H). MS (ESI4) m/z 294 [M+H]4, Ci7Hi5N3O2 requires 293.32. {3-[2-(3-Nitro-phenylamino)-pyrimidin-4-yl]-phenyl}-methanoI(91) Yield 15 %; !H-NMR (CD3OD) & 4.65 (s, 2H, CH2), 7.34-9.14 (m, 10H, Ar-H). MS (ESI4) ;M/Z 323 [M+H]+, Ci7Hi4N403 requires 322.32. [4-(4-Methoxy-phenyl)-pyrimidin-2-yl]-(3-nitro-ph&iyl)-amine(9fy Yield 43 %; 'H-NMR (CD3OD) & 3.82 (s, 3H, CH3), 6.96-9.14 (m, 10H, Ar-H). MS (ESf) m/z 323 [M+H]4, CnHi^Qs requires 322.32. 3-[4-(3-TriJluoromethyl-phenyl)-pyrimidin-2-ylamino] -phenol (95) Yield 38 %; !H-NMR (CD3OD) 5 6.76-8.71 (m, 10H, Ar-H). MS (ESI4) m/z 332 [M+H]4, d7Hi2F3N3O requires 331.29. 4- [4-(3-Trifliioromethyl-phenyl)-pyrimidin-2-ylamino] -phenol Q6) Yield 49 %; 'H-NMR (CD3OD) & 6.75-8.43 (m, 10H, Ar-H). MS (ESf) w/r 332 [M+H]4, Ci7Hi2F3N3O requires 331.29. 4-[4-(3-Methoxy-phenyl)-pyrimidin-2-ylaminoJ-phehoI(99>) Yield 25 %; 'H-NMR (CD3OD) 8: 3.92 (s, 3H, CH3), 6.89-8.38 (m, 10H, Ar-H). MS (ESI*) m/fe 294 [M+H]4, Ci7Hi5N302 requires 293.32. [4-(3~Chloro-phenyl)-pyrimidin-2-yl]-(3-nitro-phenyl)-amine(112) Yield 19 %; 1H-NMR (CD3OD) & 7.33-9.08 (m, 10H, Ar-H). MS (ESI4) JTJ/Z 326 [M+H]4, Ci6HnClN4O2 requires 326.74. 3-[4-(2>5-Difluoro-phenyl)-pyrimidin-2-ylamino]-phenol (114) Yield 17 %; *H-NMR (CD3OD) 5 6.63-8.59 (m, 10H, Ar-H). MS (ESI4) m/z 300 [M+H]4, Ci6HnF2N3O requires 299.27. {3-[2-(3-Fluoro-phenylamino)-pyrimidin-4-yl]-pheJiyl}-methanol (116) Yield 22 %;MS (ESI4) m/z 295 [M+H]4, Ci7Hi4FN3O requires 295.31. (3-Fluoro-phenyl)-[4-(3-methoxy-phenyl)-pyrimidin-2-yl]-amine (118) Yield 34 %; JH-NMR (CDC13) & 3.84 (s, 3H, CH3), 6.66-8.42 (m, 10H, Ar-H). MS (ESI4) ;w/z 296 [M+H]+, Ci7H14FN3O requires 295.31. (3-Fluoro-phenyl)-[4-(4-methoxy-phenyl)-pyrimidin-2-yl]-amine(119) Yield 34 %; 1H-NMR (CDC13) & 3.95 (s, 3H, CH3), 6.83-8.40 (m, 10H, Ar-H). MS (ESI1) m/z 296 [M+H]+, Ci7Hi4FN3O requires 295.31. 3-[2-(4-H.ydroxy-phenylamino)-pyrimidin-4-yl]-phenol (122) Yield 65 %; 'H-NMR (CD3OD) (5: 6.92-8.71 (m, 10H, Ar-H). MS MS (ESf) m/z 280 [M+Hf, C16Hi3N302 requires 279.29. Example 46 Kinase assays j The compounds from the examples ahove were investigated for their ability to inhibit the enzymatic activity of various protein kinases. This was achieved by measurement of incorporation of radioactive phosphate from ATP into appropriate polypeptide substrates. Recombinant protein kinases and kinase complexes were produced or obtained commercially. Assays were performed using 96-well plates and appropriate assay buffers (typically 25 mM p-glycerophosphate, 20 mM MOPS, 5 mM EGTA, 1 mM DTT, 1 mM Na3VO3, pH 7.4), into which were added 2 - 4 jj.g of active enzyme with appropriate substrates. The reactions were initiated by addition of Mg/ATP mix (15 mM MgCl2 + 100 HM ATP with 30-50 kBq per well of [y-32P]-ATP) and mixtures incubated as required at 30 °C. Reactions were stopped on ice, followed by filtration through p81 filterplates or GF/C filterplates (Whatman Polyfiltronics, Kent, UK). After washing 3 times with 75 mM aq orthophosphoric acid, plates were dried, scintillant added and incorporated radioactivity measured in a scintillation counter (TopCount, Packard Instruments, Pangbourne, Berks, UK). Compounds for kinase assay were made up as 10 mM stocks in DMSO and diluted into 10 % DMSO in assay buffer. Data was analysed using curve-fitting software (GraphPad Prism version 3.00 for Windows, GraphPad Software, San Diego California USA) to determine ICso values (concentration of test compound which inhibits kinase activity by 50 %.). ICso values for selected compounds of the invention are shown in Table 1. MTT cvtotoxicity assay The compounds from the examples above were subjected to a standard cellular proliferation assay using human tumour cell lines obtained from the ATCC (American Type Culture Collection, 10801 University Boulevard, Manessas, VA 20110-2209, USA). Standard 72-h MTT (thiazolyl blue; 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assays were performed [67, 68]. hi short: cells were seeded into 96-well plates according to doubling time and incubated overnight at 37 °C. Test compounds were made up in DMSO and a 1/3 dilution series prepared in 100 uL cell media, added to cells (in triplicates) and incubated for 72 ho at 37 °C. MTT was made up as a stock of 5 mg/mL in cell media and filter-sterilised. Media was removed from cells followed by a wash with 200 jjL PBS, MTT solution was then added at 20 uL per well and incubated in the dark at 37 °C for 4 h. MTT solution was removed and cells again washed with 200 uL PBS. MTT dye was solubilised with 200 jiL per well of DMSO with agitation. Absorbance was read at 540 nm and data analysed using curve-fitting software (GraphPad Prism version 3.00 for Windows, GraphPad Software, San Diego California USA) to determine ICso values (concentration of test compound which inhibits cell growth by 50 %). IC50 values for selected compounds of the invention are shown in Table 2. Various modifications and variations of the described aspects of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with specific preferred embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes of carrying out the invention which are obvious to those skilled in the relevant fields are intended to be within the scope of the following claims. 71 Table 1: Structures of exemplified compounds and inhibitory activity against various protein kinases. (Table Removed) REFERENCES 1. Manning, G.; Whyte, D. B.; Martinez, R.; Hunter, T.; Sudarsanam, S. The protein kinase complement of the human genome. Science 2002, 298,1912-1934. 2. Kostich, M.; English, J.; Madison, V.; Gheyas, F.; Wang, L. et al. Human members of the eukaryotic protein kinase family. Genome Biology 2002, 3, research0043.0041-0043.0012. 3. Dancey, J.; Sausville, E. A. Issues and progress with protein kinase inhibitors for cancer treatment. Nat. Rev. DmgDisc. 2003, 2,296-313. 4. Cockerill, G. S.; Lackey, K. E. Small molecule inhibitors of the class 1 receptor tyrosine kinase family. Current Topics in Medicinal Chemistry 2002, 2,1001-1010. 5. Fabbro, D.; Ruetz, S.; Buchdunger, E.; Cowan-Jacob, S. W.; Fendrich, G. et al. Protein kinases as targets for anticancer agents: from inhibitors to useful drugs. PharmacoLTtier. 2002, 93, 79-98. 6. Cohen, P. Protein kinases — the major drug targets of the twenty-first century? Nat. Rev. Drug Disc. 2002,1, 309-315. 7. Bridges, A. J. Chemical inhibitors of protein kinases. Chem.Rev. 2001, 101(8), 2541-2571. 8. Wang, S.; Meades, C.; Wood, G.; Osnowski, A.; Fischer, P. M. N-(4-(4- methylthiazol-5-yl) pyrirnidin-2-yl)-N-phenylamines as antiproliferative compounds. PCTIntl Patent Appl. Publ. WO 2003029248; Cyclacel Limited, UK. 9. Wu, S. Y.; McNae, L; Kontopidis, G.; McClue, S. J.; Mclnnes, C. et al. Discovery of a Novel Family of CDK Inhibitors with the Program LIDAEUS: Structural Basis forLigand-Induced Disordering of the Activation Loop. Structure 2003, 11, 399- 410. 10. Fischer, P. M.; Wang, S.; Wood, G. Inhibitors of cyclin dependent kinases as anticancer agent. PCTIntl. Patent Appl. Publ. WO 02/079193; Cyclacel Limited, UK,. 11. Wang, S.; Fischer, P. M. Anti-cancer compounds. US Patent Appl. Publ. 2002/0019404. 12. Fischer, P. M.; Wang, S. 2-substituted 4-heteroaryl-pyrimidines and their use in the treatmetn of proliferative disorders. PCTIntl. Patent Appl. Publ. WO 2001072745; Cyclacel Limited, UK. 13. Knockaert, M.; Greengard, P.; Meijer, L. Pharmacological inhibitors of cyclindependent kinases. Trends Pharmacol. Sci. 2002, 23,417 -425. 14. Fischer, P. M.; Endicott, J.; Meijer, L. Cyclin-dependent kinase inhibitors. Progress in Cell Cycle Research; Editions de la Station Biologique de Roscoff: Roscoff, France, 2003; pp 235-248. 15. Fravolini, A.; Grandolini, G.; Martani, A. New heterocyclic ring systems from ahydroxymethylene ketones. V. Reaction of 2-methyl-6-hydroxymethylene-4,5,6,7- tetrahydrobenzothiazol-7-one with amhies and amidines. Gazz. Chim. Ital. 1973, 103,1063-1071. 16. Cleaver, L.; Croft, J. A.; Ritchie, E.; Taylor, W. C. Chemical studies of the Proteaceae. IX. Synthesis of 5-alkylresorcinols from aliphatic precursors. Aust. J. Chem. 1976, 29,1989-2001. 17. Fadda, A. A.; El-Houssini, M. S. Synthesis of cyclic ketones by activated nitriles. J. Ind. Chem. Soc. 1990, 67, 915-917. 18. Kost, A. N.; Ovseneva, L. G. Synthesis of 4-substituted dihydroresorcinols. Zh. Obshch. Khim 1962, 32,3983-3986. 19. Lehmann, G.; Luecke, B.; Schick, H.; Hilgetag, G. 2-Substituted 7-oxo-4,5,6,7- tetrahydrobenzothiazoles. Z. Chem. 1967, 7,422. 20. Bell, R. P.; Davis, G. G. Kinetics of the bromination of some enols and their anions. J. Chem. Soc 1965, 353-361. 21. Fravolini, A.; Grandolini, G.; Martani, A. New heterocyclic ring systems from b> hydroxymethylene ketones. IH. Pyrazolobenzothiazoles and thiazolo- benzoisoxazoles. Gazz. Chim. Ital. 1973, 103,755-769. 22. Bredereck, H.; Effenberger, F.; Botsch, H. Acid amide reactions. XLV. Reactivity of formamidines, dimethylformamide diethyl acetal (amide acetal), and bis(dimethylamino)methoxymethane (aminal ester). Chem. Ber. 1964, 97, 3397- 3406. 23. Wang D, De la Fuente C, Deng L, Wang L, Zilberman I, Eadie C, Healey M, Stein D, Denny T, Hairison LE, Meijer L, Kashanchi F. Inhibition of human immunodeficiency virus type 1 transcription by chemical cyclin-dependent kinase inhibitors./. Virol 2001; 75: 7266-7279. 24. Chen, Y.H.; Hansen, L.; Chen, M.X.; Bjorbaek, C.; Vestergaard, H.; Hansen, T.; Cohen, P.T.; Pedersen, O. Diabetes, 1994,43,1234. 25. Nikoulina, S.E.; Ciaraldi, T.P.; Mudaliar, S.; Mohideen, P.; Carter, L.; Henry, R.R. Diabetes, 2000,49, 263. 26. Goedert, M. Curr. Opin. Gen. Dev., 2001,11,343. 27. Mattson, M.P. Nat. Rev. Mol. Cell. Biol., 2000,1,120. 28. Zhu, A.J.; Watt, P.M. Development, 1999,126,2285. 29. DasGupta, R.; Fuchs, E. Development, 1999,126,4557. 30. Sunkel et al, J. Cell ScL, \ 988, 89,25. 31. Llamazares et al., Genes Dev., 1991,5,2153. 32. Glover et al., Genes Dev., 1998,12,3777. 33. Lee et al., Proc. Natl. Acad. Sci. USA, 1998,95,9301. 34. Lexmgetal, Nat. Struct. Biol., 2002,9,719. 35. Kauselmann et al., EMBOJ., 1999,18, 5528. 36. Nigg, Curr. Opin. Cell Biol., 1998,10, 776. 37. Yuan et al., Cancer Res., 2002, 62,4186. 38. Seong et al., J. Biol Chem., 2002,277, 32282. 39. Lane et al., J. Cell. Biol, 1996,135,1701. 40. Cogswell et al., Cell Growth Differ., 2000,11,615. 41. Liu et al., Proc. Natl Acad. Sci. USA, 2002,99,8672. 42. Toyoshima-Morimoto et al., Nature, 2001,410,215. 43. Roshak et al., Cell Signalling, 2000,12,405. 44. Smits et al., Nat. Cell Biol, 2000,2,672. 45. van Vugt et al., J. Biol Chem., 2001, 276, 41656. 46. Sumara et al., Mol Cell, 2002,9, 515. 47. Golan et al., J. Biol Chem., 2002,277,15552. 92 48. Kotani et al., Mol Cell, 1998,1, 371. 49. Feng et al., Cell Growth Differ., 2001,12,29. 50. Dai et al., Oncogene, 2002,21, 6195. 51. Nurse, Nature, 1990, 344, 503. 52. Nigg, Nat. Re^>. Mol. Cell BioL, 2001,2,21. 53. Hagting et al., EMBO J., 1998,17,4127. 54. Hagting et al., Curr. BioL, 1999,9, 680. 55. Yang et al., J. BioL Chem., 2001, 276, 3604. 56. Takizawa et al., Curr. Opin. Cell BioL, 2000,12,658. 57. Seki et al., Mol. BioL Cell, 1992,3,1373. 58. Heald et al., Cell, 1993,74,463. 59. Dalai et al., Mol. Cell. BioL, 1999,19,4465. 60. Toyoshima-Morimoto et al., Nature, 2001,410,215. 61. Toyoshima-Morimoto et al., EMBO Rep., 2002, 3, 341. 62. Wang et al., Mol. Cell. BioL, 2002, 22,3450. 63. Tyrrell, E.; Brookes, P. Synthesis 2003,469-483. 64. Molander, G." A.; Biolatto, B. J. Org. Chem. 2003,68,4302-4314. 65. Bredereck, H.; Effenberger, F.; Botsch, H. Chem. Ber. 1964, 97,3397-3406. 66. Zimmermann, J.; Caravatti, G.; Mett, H.; Meyer, T.; Miiller, M. et al. Arch. Pharm. Pharm. Med. Chem. 1996, 329,371-376. 67. Haselsberger, K.; Peterson, D. C.; Thomas, D. G.; Darh'ng, J. L. Anti Cancer Drugs 1996,7,331-8. 68. Loveland, B. E.; Johns, T. G.; Mackay, I. R.; Vaillant, F.; Wang, Z. X.; Hertzog, P. J. Biochemistry International 1992,27, 501-10. We Claim: 1. A compound, or pharmaceutically acceptable salt thereof, which is selected from the following: [4-(3-Amino-phenyl)-pyrimidin-2-yl]-[4-(2-methoxy-ethoxy)-phenyl]-amine [3]; [4-(3-Amino-phenyl)-pyrimidine-2-yl] -(3-nitro-phenyl)-amine [19]; [4-(3-Ethylamino-phenyl)-pyrimidine-2-yl]-(4-methoxy-phenyl)-amine [25]; (3-Nitro-phenyl)-[4-(3-[l,2,4]triazol-l-ylmethyl-phenyl)-pyrimidin-2-yl]-amine [30]; 3-[4-(3[l,2,4]Triazol-l-ylmethyl-phenyl)-pyrimidin-2-ylamino]-benzonitrile [36]; N-{3-[2-(3-Nitro-phenylamino)-pyrimidin-4-yl]-benzyl}-methanesulfonamide [40]; (4-{3-[(Ethyl-isopropyl-amino)-methyl]-phenyl}-pyrimidine-2-yl)-(3-nitro-phenyl)-amine [46]; (4-{3-[(Ethyl-isopropyl-amino)-methyl]-phenyl}-pyrimidine-2-yl)-(6-methoxy-P5aidin-3-yl)-amine [53]; {4[3-(4-Methyl-piperazin-l-ylmethyl)-phenyl]-pyrimidin-2-yl}-(3-nitro-phenyl)-amine [54]; 3-[2-(3-Nitro-phenylamino)-pyrimidin-4-yl]-phenol [55]; [4-(3-Dimethylaminomethyl-phenyl)-pyrimidine-2-yl]-(3-nitro-phenyl)-amine [71]; 3-[4-(4-Methoxy-phenyl)pyrimidin-2-ylamino]-phenol [76]; (l-{3-[2-(3-Nitro-phenylamino)-pyrimidin-4-yl]-benzyl}-piperidin-2-yl)-methanol [79]; 3-[4-(3-Dimethylaminomethyl-phenyl)-pyrimidine-2-ylamino]-phenol [80]; 4-[4-(3-Dimethylaminomethyl-phenyl)-pyrimidine-2-ylamino]-phenol [81]; [4-(3-Dimethylaminomethyl-phenyl)-pyrimidine-2-yl]-(6-methoxy-pyridin-3-yl)-amine [83]; [4-(3-Dimethylaminomethyl-phenyl)-pyrimidine-2-yl]-(3-nitro-phenyl)-amine [84]; [4-(3-Methoxy-phenyl)-pyrimidine-2-yl]-(3-nitro-phenyl)-amine [87]; 3-[4-(3-Methoxy-phenyl)-pyrimidine-2-ylamino]-phenol [88]; {3-[2-(3-Nitro-phenylamino)-pyrimidin-4-yl]-phenyl}-methanol [91]; [4-(4-Methoxy-phenyl)-pyrimidine-2-yl]-(3-nitro-phenyl)-amine [94]; 4-[4-(3-Methoxy-phenyl)-pyrimidine-2-ylamino]-phenol [98]; 1 l-{3-[2-(3-Nitro-phenylamino)-pyrimidin-4-yl]-benzyl}-piperidine-3-carboxylic acid amide [99]; 2-(l-{3-[2-(3-Nitro-phenylamino)-pyrimidine-4-yl]-benzyl}-piperidin-3-yl)-ethanol [100]; (l-{3-[2-(3-Nitro-phenylamino)-pyrimidin-4-yl]-benzyl}-piperidin-3-yl)-methanol [105]; (l-{3-[2-(4-Methyl-3-nitro-phenylamino)-pyrimidin-4-yl]-benzyl}-piperidin-2-yl)-methanol [108]; 4-[4-(4-Methoxy-phenyl)-pyrimidin-2-ylamino]-phenol [110]; (3-Fluoro-phenyl)-[4-(3-methoxy-phenyl)-pyrimidin-2-yl]-am.ine [118]; [4-(4-Methoxy-phenyl)-pyrimidin-2-yl]-(6-methoxy-pyridin-3-yl)-amine [124]; [4-(4-Methoxy-phenyl)-pyrimidin-2-yl]-(3,4,5-trimethoxy-phenyl)-amine [128]; N-Methyl-N-{3-[2-(3-nitro-phenylamino)-pyrimidin-4-yl]-phenyl}-methanesulfonamide [129]; N-{3-[2-(3-Hydroxy-phenylamino)-pyrimidin-4-yl]-phenyl}-N-methyl-methanesulfonamide [130]; and N-{3-[2-(4-Hydroxy-phenylamino)-pyrimidin-4-yl]-phenyl}-N-methyl-methanesulfonamide [131]. 2. A pharmaceutical composition for treating a proliferative disorder, comprising a compound as claimed in claim 1 admixed with a pharmaceutically acceptable diluent, excipient or carrier. 3. A pharmaceutical composition as claimed in claim 2 wherein the proliferative disorder is cancer or leukemia. 4. A pharmaceutical composition as claimed in claim 2 wherein the proliferative disorder is glomerulonephritis, rheumatoid arthritis, psoriasis or chronic obstructive pulmonary disorder.

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