Pyrimidines as PLK inhibitors

A method of preparing a pharmaceutical composition, comprising:

• forming a compound of the following formula (1):
• wherein
• W denotes N or C—R2,
• X denotes —NR1a, O or S,
• Y denotes CH or N,
• Z denotes one of hydrogen, halogen, —NO2, C1-3alkyl, C2-3alkenyl, C2-3alkynyl, halogen-C1-3alkyl, —COH, —C(═O)—C1-3alkyl, —C(═O)—C2-3alkenyl, —C(═O)—C2-3alkynyl, —C(═O)C1-3alkyl-halogen and pseudohalogen;
• A is selected from one of the following formulas (i), (ii) and (iii):
• Q1 denotes mono- or bicyclic aryl compounds;
• B1, B2, B3 and B4 each independently denote C—RgRh, N—Ri, O or S;
• R1 and R1a each independently denote hydrogen or methyl;
• R2 denotes one of hydrogen, halogen, —OR4, —C(═O)R4, —C(═O)NR4R5, —NR4R5, —NR4C(═O)R5, —NR4SO2R5, —N═CR4R5, —C═NRi, —SR4, —SOR4, —SO2R4, —SO2NR4R5, pseudohalogen, and a mono- or polysubstituted group selected from the group consisting of C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6-cycloalkyl, aryl, heterocyclyl and heteroaryl, wherein the substituent(s) of the mono- or polysubstituted group are identical or different and are selected from the group consisting of halogen, —NO2, —OR4, —C(═O)R4, —C(═O)OR4, —C(═O)NR4R5, —NR4R5, —NR4C(═O)R5, —NR4C(═O)OR5, —NR4C(═O)NR5R6, —NR4SO2R5, —N═CR4R5, —SR4, —SOR4, —SO2R4, —SO2NR4R5, —NR4SO2NR5R6, —OSO2NR5R6 and pseudohalogen;
• Ra, Rb, Rc, Rd, Re, Rf, Rg and Rh each independently of one another denote a group selected from the group consisting of hydrogen, halogen, ═O, —NO2, —OR4, —C(═O)R4, —C(═O)OR4, —C(═O)NR4R5, —NR4R5, —NR4C(═O)R5, —NR4C(═O)OR5, —NR4C(═O)NR5R6, —NR4SO2R5, —N═CR4R5, —C═NRi, —SR4, —SOR4, —SO2R4, —SO2NR4R5, —NR4SO2NR5R6, —OSO2NR5R6, pseudohalogen, and an unsubstituted or mono- or polysubstituted group selected from the group consisting of C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-6-cycloalkyl, aryl, heterocyclyl and heteroaryl, wherein the substituent(s) of the mono- or polysubstituted group are identical or different and are selected from the group consisting of halogen, R8, —NO2, —OR4, —C(═O)R4, —C(═O)OR4, —C(═O)NR4R5, —NR4R5, —NR4C(═O)R5, —NR4C(═O)OR5, —NR4C(═O)NR5R6, —NR4SO2R5, —N═CR4R5, —SR4, —SOR4, —SO2R4, —SO2NR4R5, —NR4SO2NR5R6, —OSO2NR5R6 and pseudohalogen;
• wherein Rg and Rh are optionally located at the same or at adjacent C atoms and are attached in any combination to a common saturated or partially unsaturated 3-5-membered alkyl bridge which contains one to two heteroatoms;
• Ri denotes a group selected from the group consisting of hydrogen, ═O, —OR4, —C(═O)R4, —C(═O)OR4, —C(═O)NR4R5, —NR4R5, —NR4C(═O)R5, —NR4C(═O)OR5, —NR4C(═O)NR5R6, —NR4SO2R5, —N═CR4R5, —SR4, —SOR4, —SO2R4, —SO2NR4R5, —NR4SO2NR5R6, —OSO2NR5R6, pseudohalogen and an unsubstituted or substituted mono- or polysubstituted group selected from the group consisting of C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, aryl, heterocyclyl and heteroaryl, wherein the substituent(s) of the mono- or polysubstituted group are identical or different and are selected from the group consisting of halogen, R8, —NO2, —OR4, —C(═O)R4, —C(═O)OR4, —C(═O)NR4R5, —NR4R5, —NR4C(═O)R5, —NR4C(═O)OR5, —NR4C(═O)NR4R5, —NR4SO2R5, —N═CR4R5, —SR4, —SOR4, —SO2R4, —SO2NR4R5, —NR4SO2NR5R6, —OSO2NR5R6 and pseudohalogen;
• wherein the Ri groups located at adjacent N atoms are optionally joined together or Ri with Rg or Rh located at adjacent C atoms are optionally attached in any combination to a common saturated or partially unsaturated 3-5-membered alkyl bridge which contains one to two heteroatoms;
• R3 is selected from the following formulas (iv)-(x):
• R4, R5 and R6 each independently of one another denote hydrogen or an unsubstituted or mono- or polysubstituted group selected from the group consisting of C1-5-alkyl, C2-5alkenyl, C2-5alkynyl, C3-10cycloalkyl, aryl, heterocyclyl and heteroaryl, wherein the substituent(s) may bc of the mono- or polysubstituted group are identical or different and are selected from the group consisting of C3-10-cycloalkyl, aryl, heterocyclyl, heteroaryl, halogen, —NO2, —OR8, —C(═O)R8, —C(═O)OR8, —C(═O)NR8R9, —NR8R9, —NR8C(═O)R9, —NR8C(═O)OR9, —NR8C(═O)NR9R10, —NR8C(═O)ONR9R10, —NR8SO2R9, —N═CR8R9, —SR8, —SOR8, —SO2R8, —SO2NR8R9, —NR8SO2NR9R10, —OSO2NR8R9 and pseudohalogen;
• L denotes a bond or an unsubstituted or mono- or polysubstituted group selected from the group consisting of C1-16-alkyl, C2-16-alkenyl, C2-16-alkynyl, C3-10-cycloalkyl, aryl, heterocyclyl and heteroaryl, wherein the substituent(s) of the mono- or polysubstituted group are identical or different and are selected from the group consisting of halogen, —NO2, —OR8, —C(═O)R8, —C(═O)OR8, —C(═O)NR8R9, —NR8R9, —NR8C(═O)R9, —NR8C(═O)OR9, —NR8C(═O)NR9R10, —NR8C(═O)ONR9R10, —NR8SO2R9, —N═CR8R9, —SR8, —SOR8, —SO2R8, —SO2NR8R9, —NR8SO2NR9R10, —OSO2NR8R9 and pseudohalogen;
• Q2 and Q3 each independently of one another denote a bond or an unsubstituted or mono- or polysubstituted group selected from the group consisting of C1-16-alkyl, C2-16-alkenyl, C2-16-alkynyl, C3-10-cycloalkyl, aryl, heterocyclyl and heteroaryl, wherein the substituent(s) may be of the mono- or polysubstituted group are identical or different and are selected from the group consisting of halogen, —NO2, —OR8, —C(═O)R8, —C(═O)OR8, —C(═O)NR8R9, —NR8R9, —NR8C(═O)R9, —NR8C(═O)OR9, —NR8C(═O)NR9R10, —NR8C(═O)ONR9R10, —NR8SO2R9, —N═CR8R9, —SR8, —SOR8, —SO2R8, —SO2NR8R9, —NR8SO2NR9R10, —OSO2NR8R9 and pseudohalogen;
• R7 denotes hydrogen or an unsubstituted or mono- or polysubstituted group selected from the group consisting of C1-16-alkyl, C2-16-alkenyl, C2-16-alkynyl, C3-10-cycloalkyl, aryl, heterocyclyl and heteroaryl, wherein the substituent(s) of the mono- or polysubstituted group are identical or different and are selected from the group consisting of halogen, NO2, —OR8, —C(═O)R8, —C(═O)OR8, —C(═O)NR8R9, —NR8R9, —NR8COR9, —NR8C(═O)OR9, —NR8C(═O)NR9R10, —NR8C(═O)ONR9R10, —NR8SO2R9, —N═CR8R9, —SR8, —SOR8, —SO2R8, —SO2NR8R9, —NR8SO2NR9R10, —OSO2NR8R9 and pseudohalogen;
• and
• R8, R9 and R10 each independently of one another denote hydrogen or a substituted or unsubstituted group selected from the group consisting of C1-8-alkyl, C2-8-alkenyl, C2-8-alkynyl, C3-10-cycloalkyl, aryl, heterocyclyl and heteroaryl, wherein the substituent(s) of the substituted group are identical or different and are selected from the group consisting of halogen, methyl, ethyl, amino, methylamino, dimethylamino, —OH and pseudohalogen;
• wherein the compound is optionally in the form of tautomers, racemates, enantiomers, diastereomers and mixtures thereof, and optionally the pharmacologically acceptable acid addition salts thereof;
• and
• combining the compound with at least one cytostatic or cytotoxic active substance.