AU2006239444A1

AU2006239444A1 - New thiazolidinones without basic nitrogen, their production and use as pharmaceutical agents

Info

Publication number: AU2006239444A1
Application number: AU2006239444A
Authority: AU
Inventors: Dominic E.A. Brittain; Uwe Eberspaecher; Knut Eis; Judith Guenther; Dirk Kosemund; Olaf Prien; Volker Schulze; Gerhard Siemeister; Lars Wortmann
Original assignee: Bayer Schering Pharma AG
Current assignee: Bayer Pharma AG
Priority date: 2005-04-25
Filing date: 2006-04-24
Publication date: 2006-11-02
Also published as: ZA200710147B; EP1874744A1; RU2007143513A; MX2007013306A; DE102005020105A1; CA2605760A1; JP2008538756A; KR20080005971A; CN101208317A; IL186747A0; BRPI0610832A2; NO20076038L; WO2006114334A1

Description

WO 2006/114334 PCT/EP2006/004226 New Thiazolidinones without Basic Nitrogen, Their Production and Use as Pharmaceutical Agents The invention relates to thiazolidinones, to their production and to their use as 5 inhibitors of polo-like kinases (Plk) for treating various diseases. Tumour cells are distinguished by an uninhibited cell-cycle process. On the one hand, this is based on the loss of control proteins, such as RB, p16, p21, p53, etc., as well as the activation of so-called accelerators of the cell-cycle process, the 10 cyclin-dependent kinases (Cdks). The Cdks are an anti-tumour target protein that is acknowledged in pharmaceutics. In addition to the Cdks, serine/threonine kinases that regulate the new cell cycle, so-called 'polo-like kinases,' were described, which are involved not only in the regulation of the cell cycle but also in the coordination with other processes during mitosis and cytokinesis (formation of the 15 spindle apparatus, chromosome separation). This class of proteins therefore represents an advantageous point of application for therapeutic intervention of proliferative diseases such as cancer (Descombes and Nigg. Embo J, 17; 1328 et seq., 1998; Glover et al. Genes Dev 12, 3777 et seq., 1998). 20 A high expression rate of Plk-1 was found in 'non-small cell lung' cancer (Wolf et al. Oncogene, 14, 543 et seq., 1997), in melanomas (Strebhardt et al. JAMA, 283, 479 et seq., 2000), in 'squamous cell carcinomas' (Knecht et al. Cancer Res, 59, 2794 et seq., 1999) and in 'esophageal carcinomas' (Tokumitsu et al. Int J Oncol 15, 687 et seq., 1999). 25 A correlation of a high expression rate in tumour patients with poor prognosis was shown for the most varied tumours (Strebhardt et al. JAMA, 283, 479 et seq., 2000, Knecht et al. Cancer Res, 59, 2794 et seq., 1999 and Tokumitsu et al. Int J Oncol 15, 687 et seq., 1999). 30 The constitutive expression of Plk-1 in NIH-3T3 cells resulted in a malignant transformation (increased proliferation, growth in soft agar, colony formation and tumour development in hairless mice) (Smith et al. Biochem Biophys Res Comm, 234, 397 et seq., 1997).

2 WO 2006/114334 PCT/EP2006/004226 Microinjections of Plk-1 antibodies in HeLa cells resulted in improper mitosis (Lane et at.; Journal Cell Biol, 135, 1701 et seq., 1996). 5 With a '20-mer' antisense oligo, it was possible to inhibit the expression of Plk-1 in A549 cells, and to stop their ability to survive. It was also possible to show a significant anti-tumour action in hairless mice (Mundt et al., Biochem Biophys Res Comm, 269, 377 et seq., 2000). 10 The microinjection of anti-Plk antibodies in non-immortalized human Hs68 cells showed, in comparison to HeLa cells, a significantly higher fraction of cells, which remained in a growth arrest at G2 and showed far fewer signs of improper mitosis (Lane et aL.; Journal Cell Biot, 135, 1701 et seq., 1996). 15 In contrast to tumour cells, antisense-oligo-molecules did not inhibit the growth and the viability of primary human mesangial cells (Mundt et aL., Biochem Biophys Res Comm, 269, 377 et seq., 2000). In mammals, to date in addition to the Plk-1, three other polo-kinases were 20 described that are induced as a mitogenic response and exert their function in the G1 phase of the cell cycle. These are, on the one hand, the so-called Prk/Plk-3 (the human homolog of the mouse-Fnk = fibroblast growth factor-induced kinase; Wiest et at, Genes, Chromosomes t Cancer, 32: 384 et seq., 2001), Snk/Plk-2 (Serum-Induced Kinase, Liby et aL., DNA Sequence, 11, 527-33, 2001) and sak/Plk4 25 (Fode et aL., Proc. NatL Acad. Sci. U.S.A., 91, 6388 et seq; 1994). The inhibition of Plk-1 and the other kinases of the polo family, such as Plk-2, Plk-3 and Plk-4, thus represents a promising approach for the treatment of various diseases. 30 The sequence identity within the Plk domains of the polo family is between 40 and 60%, so that partial interaction of inhibitors of a kinase occurs with one or more other kinases of this family. Depending on the structure of the inhibitor, however, WO 2006/114334 3 PCT/EP2006/004226 the action can also take place selectively or preferably on only one kinase of the polo family. In International Application WO 03/093249, thiazolidinone compounds that inhibit 5 the kinases of the polo family are disclosed. The object of this invention is now to make available additional substances that inhibit kinases of the polo family in the micro- and nanomolar range. 10 It has now been found that compounds of general formula I A 0 Q X-R 2 B N CN \ R ( I ), 15 in which Q stands for aryl, A and B, independently of one another, stand for hydrogen, halogen, hydroxy,

-NR

3

R

4 , cyano or nitro, or 20 for C-C 4 -alkyl, C-C 6 -alkoxy or C 3

-C

6 -heterocycloalkyl that optionally is substituted in one or more places, in the same way or differently, with halogen, hydroxy, C 3

-C

6 -heterocycloalkyl or with the group -NR 3

R

4 or

-CO(NR

3 )-M, whereby the heterocycloalkyl itself optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms 25 and/or optionally can be interrupted by one or more -C(O)- or -SO 2 groups in the ring and/or optionally one or more double bonds can be contained in the ring and/or the ring itself optionally can be substituted in one or more places, in the same way or differently, with

C,-C

6 -alkyl, C 3

-C

6 -cycloalkyl, Cl-C 6 -hydroxyalkyl or with the group 30

-NR

3

R

4

,

WO 2006/114334 PCT/EP2006/004226 or for -NR 3 C(O)-L, -NR 3 C(0)-NR 3 -L, -COR 6 , -0-(CH 2 )pR 6 , -CO(NR 3 )-M,

-NR

3

(CS)NR

3

R

4 , -NR 3

SO

2 -M, -SO 2

-NR

3

R

4 , - S0 2

(NR

3 )-M or -0-(CH 2 )paryl, p stands for an integer of 0, 1, 2, 3, or 4, 5 L stands for C-C 6 -alkyl or C 3

-C

6 -heterocycloalkyl that optionally is substituted in one or more places, in the same way or differently, with

C

1

-C

6 -hydroxyalkoxy, C-C 6 -alkoxyalkoxy, C 3

-C

6 -heterocycloalkyl or with the group -NR 3

R

4 , whereby the heterocycloalkyl itself optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur 10 atoms and/or optionally can be interrupted by one or more -C(O)- or -S0 2 - groups in the ring and/or optionally one or more double bonds can be contained in the ring, and/or the ring itself optionally can be substituted in one or more places, in the same way or differently, with Ci-C 6 -alkyl, C 3

-C

6 -cycloalkyl, C-C 6 -hydroxyalkyl or with the group 15

-NR

3

R

4 , M stands for C-C 6 -alkyl that optionally is substituted in one or more places, in the same way or differently, with the group -NR 3

R

4 or C 3

-C

6 heterocycloalkyl, X stands for -NH- or -NR 5 20 R 1 stands for C-C 4 -alkyt, C 3 -cycloalkyl, allyl or propargyl that optionally is substituted in one or more places, in the same way or differently, with halogen,

R

2 stands for hydrogen or for C-C 6 -alkyl, C-C 6 -alkoxy, C-C 6 -alkenyl,

C

1

-C

6 -alkynyl, C 3

-C

6 -cycloalkyl, C 3

-C

6 -heterocycloalkyl, aryl or 25 heteroaryl that optionally is substituted in one or more places, in the same way or differently, with halogen, hydroxy, cyano, C-C 6 -alkyl,

C,-C

6 -alkoxy, C-C 6 -hydroxyalkyl, C 3

-C

6 -cycloalkyl, CrC6 heterocycloalkyl, C-C 6 -alkynyl, aryl, aryloxy, heteroaryl or with the group -S-C-C 6 -alkyl, -COR 6 , -NR 3

R

4 , -NR 3 C(O)-L or -NR 3

COOR

7 , 30 whereby the heterocycloalkyl itself optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms and/or optionally can be interrupted by one or more -C(O)- or -SO 2 groups in the ring and/or optionally one or more double bonds can be contained in the ring, WO 2006/114334 5 PCT/EP2006/004226 and whereby aryl, heteroaryl, C 3

-C

6 -cycloalkyl- and/or the C 3

-C

6 heterocycloalkyl ring in each case itself optionally can be substituted in one or more places, in the same way or differently, with cyano, halogen, hydroxy, CI-C 6 -alkyl, C-C 6 -hydroxyalkyl, or C 1

-C

6 -alkoxy, 5 C 3

-C

6 -cycloalkyl, C 3 -C-heterocycloalkyl, aryl, benzyl or heteroaryl that optionally is substituted in one or more places, in the same way or differently, with halogen, or for the group -NR 3

R

4 , -NR 3 C(0)-L, or -NR 3

(CS)NR

3

R

4 , 10 or

R

2 and R 5 together form a C 3

-C

6 -heterocycloalkyl ring, which is interrupted at least once by nitrogen and optionally can be interrupted in one or more places by oxygen or sulfur and/or optionally can be interrupted by one or more -C(O)- or -SO 2 - groups in the ring and/or optionally one 15 or more double bonds can be contained in the ring, and/or the ring itself optionally can be substituted in one or more places, in the same way or differently, with cyano, halogen, hydroxy, Cl-C 6 -alkyl, C 3

-C

6 -cycloalkyl, C-C 6 -hydroxyalkyl, C-C 6 -alkoxyalkyl or with the group -NR 3

R

4 or -COR , 20 and/or can be substituted with aryl or heteroaryl that optionally is substituted in one or more places, in the same way or differently, with halogen, C-C 6 -alkoxy or with the group -COR ,

R

3 and R 4 , independently of one another, stand for hydrogen or for C-C 6 -alkyl, Cl-C 6 -alkoxy, -CO-C-C 6 -alkyl or aryl that optionally is substituted in 25 one or more places, in the same way or differently, with halogen, hydroxy, C 3

-C

6 -heterocycloalkyl, C-C 6 -hydroxyalkoxy or with the group

-NR

3

R

4 , whereby the heterocycloalkyl itself optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms and/or optionally can be interrupted by one or more -C(O)- or -SO2 30 groups in the ring and/or optionally one or more double bonds can be contained in the ring, and whereby the C 3

-C

6 -heterocycloalkyl ring itself optionally can be substituted in one or more places, in the same way or differently, with cyano, halogen, C-C 6 -alkyl, C-C 6

-

WO 2006/114334 6 PCT/EP2006/004226 hydroxyalkyl, C-C 6 -alkoxy, C 3

-C

6 -cycloalkyl, or with the group -NR 3

R

4 or -CO-NR 3

R

4 , or

R

3 and R 4 together form a C 3

-C

6 -heterocycloalkyl ring, which is interrupted at 5 least once by nitrogen and optionally can be interrupted in one or more places by oxygen or sulfur and/or optionally can be interrupted by one or more -C(O)- or -S02- groups in the ring and/or optionally one or more double bonds can be contained in the ring, and/or the heterocycloalkyl ring itself optionally can be substituted in 10 one or more places, in the same way or differently, with C-C 6 -alkyl,

C

3

-C

6 -cycloalkyl, C-C 6 -hydroxyalkyl, C-C 6 -alkoxyalkyl, cyano, hydroxy or with the group -NR 3

R

4 , R stands for C-C 6 -alkyl, C-C 6 -alkenyl, or C 1

-C

6 -alkynyl that optionally is substituted in one or more places, in the same way or differently, with 15 halogen, hydroxy, cyano, C-C 6 -alkoxy, C 3

-C

6 -cycloalkyl, C 3

-C

6 heterocycloalkyl, or with the group -NR 3

R

4 , whereby the heterocycloalkyl itself optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms and/or optionally can be interrupted by one or more -C(0)- or -S0 2 groups in the ring and/or 20 optionally one or more double bonds can be contained in the ring, and whereby the C 3

-C

6 -heterocycloalkyl ring itself in each case optionally can be substituted in one or more places, in the same way or differently, with cyano, halogen, C-C 6 -alkyl, C-C 6 -hydroxyalkyl, Cl-C 6 -alkoxy, C 3

-C

6 -cycloalkyl, or with the group -NR 3

R

4 or -CO-NR 3

R

4 , 25 R 6 stands for hydroxy, C-C 6 -alkyl, C-C 6 -alkoxy or the group -NR 3

R

4 , RI stands for -(CH 2 )n-aryl or -(CH 2 )n-heteroaryl, and n stands for an integer of 1, 2, 3, 4, 5 or 6, as well as the solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts thereof, 30 are suitable inhibitors of the kinases of the polo family. This is surprising, since compounds of general formula I do not have the donor acceptor motif of the generally known kinase inhibitors that is quite well known and well established from the literature (cf. Structure 1999, Vol. 3, pp. 319, and WO 2006/114334 PCT/EP2006/004226 Science 1998, Vol. 281, p. 533) and that makes possible adequate binding to the hinge region in the catalytic center of the kinase. It is therefore possible, but not absolutely necessary, that compounds of general formula I bind in some other way to the kinases and cause such an inhibitory action. 5 The compounds of general formula I according to the invention essentially inhibit the polo-like kinases, upon which is based their action against, for example, cancer, such as solid tumours and leukemia; auto-immune diseases, such as psoriasis, alopecia, and multiple sclerosis, chemotherapy agent-induced alopecia 10 and mucositis; cardiovascular diseases, such as stenoses, arterioscleroses and restenoses; infectious diseases, such as those, e.g., produced by unicellular parasites, such as trypanosoma, toxoplasma or plasmodium, or produced by fungi; nephrological diseases, such as, e.g., glomerulonephritis; chronic neurodegenerative diseases, such as Huntington's disease, amyotropic lateral 15 sclerosis, Parkinson's disease, AIDS dementia and Alzheimer's disease; acute neurodegenerative diseases, such as ischemias of the brain and neurotraumas; viral infections, such as, e.g., cytomegalic infections, herpes, hepatitis B and C, and HIV diseases. 20 Stereoisomers are defined as E/Z- and R/S-isomers as well as mixtures that consist of E/Z- and R/S-isomers. The following terms used in the decription and the claims have preferably the following meanings 25 The term "alkyl" is defined in each case as a straight-chain or branched alkyl radical, such as, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec.

butyl, tert.-butyl, pentyl, isopentyl, hexyl, heptyl, octyl, nonyl and decyl, and the isomers thereof. 30 The term "alkoxy" is defined in each case as a straight-chain or branched alkoxy radical, such as, for example, methoxy, ethoxy, propyloxy, isopropyloxy, butyloxy, isobutyloxy, sec.-butyloxy, tert-butyloxy, pentyloxy, isopentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy or decyloxy, and the isomers thereof.

WO 2006/114334 8 PCT/EP2006/004226 The term "alkenyl" is defined in each case as a straight-chain or branched alkenyl group, whereby, for example, the following radicals are meant: vinyl, propen-1-yl, propen-2-yl, but-1-en-1-yl, but-1-en-2-yl, but-2-en-1-yl, but-2-en-2-yl, 2-methyl 5 prop-2-en-1 -yl, 2-methyl-prop-1 -en-1 -yl, but-1 -en-3-yt, but-3-en-1 -yl, and allyl. The term "alkynyl" is defined in each case as a straight-chain or branched alkynyl radical that contains 2 to 6, preferably 2 to 4, C atoms. For example, the following radicals can be mentioned: acetylene, propyn-1-yl, propyn-3-yl, but-1-yn-1-yl, but 10 1-yn-4-yl, but-2-yn-1-yl, but-1-yn-3-yt, etc. The term "heterocycloalkyl" stands for an alkyl ring that comprises 3 to 6 carbon atoms, in which one or more carbon contains is (are) replaced by one or more heteroatoms that are the same or different, such as, e.g., oxygen, sulfur or 15 nitrogen and/or optionally can be interrupted by one or more -C(O)- or -SO 2 - groups in the ring, and/or optionally one or more double bonds can be contained in the ring, and can contain another substituent on one or more carbon, nitrogen or sulfur atoms, optionally independently of one another. Substituents on the heterocycloalkyl ring can be: cyano, halogen, hydroxy, C-C 6 -alkyl, C-C 6 -alkoxy, 20 C-C 6 -alkoxyalkyt, Cl-C 6 -hydroxyalkyl, C 3 -C-cycloalkyl, aryt, or the group -NR 3

R

4 ,

-CO-NR

3

R

4 , -S0 2

R

3 or -SO 2

NR

3

R

4 . As heterocycloalkyls, there can be mentioned, e.g.: oxiranyl, oxethanyl, aziridinyl, azetidinyl, tetrahydrofuranyl, pyrrolidinyl, dioxolanyl, imidazolidinyl, pyrazolidinyl, 25 dioxanyl, piperidinyl, morpholinyl, dithianyl, thimorpholinyl, piperazinyl, trithianyl, quinuclidinyl, pyrolidonyl, N-methylpyrolidinyl, 2-hydroxymethylpyrolidinyl, 3 hydroxypyrolidinyl, N-methylpiperazinyl, N-acetylpiperazinyt, N methylsulfonylpiperazinyl, 4-hydroxypiperidinyl, 4-aminocarbonylpiperidinyl, 2 hydroxyethylpiperidinyl, 4-hydroxymethylpiperidinyl, nortropynyl, 1,1 -dioxo 30 thiomorpholinyL, etc. The term "cycloalkyl" is defined as a monocyclic alkyl ring, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl, but also bicyclic rings or tricyclic WO 2006/114334 PCT/EP2006/004226 rings, such as, for example, adamantanyl. The cycloalkyl can optionally also be benzocondensed, such as, e.g., (tetralin)yl, etc. The term "halogen" is defined in each case as fluorine, chlorine, bromine or iodine. 5 As used herein, the term "aryl" is defined in each case as having 3 to 12 carbon atoms, preferably 6 to 12 carbon atoms, such as, for example, cyclopropenyl, cyclopentadienyl, phenyl, tropyl, cyclooctadienyl, indenyl, naphthyl, azulenyl, biphenyls, fluorenyl, anthracenyl etc, phenyl being preferred. 10 As used herein, the term "heteroaryl" is understood as meaning an aromatic ring system which comprises 3 to 16 ring atoms, preferably 5 or 6 or 9 or 10 atoms, and which contains at least one heteroatom which may be identical or different, said heteroatom being such as oxygen, nitrogen or sulfur, and can be monocyclic, 15 bicyclic, or tricyclic, and in addition in each case can be benzocondensed. Preferably, heteroaryl is selected from thienyl, furanyl, pyrrolidinyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, thia-4H-pyrazoyl etc., and benzo derivatives thereof, such as, e.g., benzofuranyl, benzothienyl, benzoxazolyl, benzimidazolyt, benzotriazolyt, 20 indazolyl, indolyl, isoindolyl, etc.; or pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, etc., and benzo derivatives thereof, such as, for example, quinolinyl, isoquinolinyl, etc.; or oxepinyl, azocinyl, indolizinyl, indolyl, indolinyl, isoindolyl, indazolyl, benzimidazoyl, purinyl, etc., and benzo derivatives thereof; or quinolinyl, isoquinolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthpyridinyl, 25 pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, xanthenyl, or oxepinyl, etc. Preferred heteroaryl radicals are, for example, 5-membered ring heterocycles, such as thiophene, furanyl, oxazolyl, thiazole, imidazolyl and benzo derivatives thereof, 30 and 6-membered ring heterocycles, such as pyridinyl, pyrimidinyl, triazinyl, quinolinyl, isoquinolinyl and benzo derivatives thereof.

WO 2006/114334 10 PCT/EP2006/004226 As used herein, the term "C-C 6 ", as used throughout this text, e.g. in the context of the definition of "C-C 6 -alkyl", "C-C 6 -alkoxy", "C-C 6 -hydroxyalkyl", "C-C 6 hydroxyalkoxy", or "C-C 6 -alkoxyalkoxy", etc., is to be understood as meaning an alkyl group having a finite number of carbon atoms of 1 to 6, i.e. 1, 2, 3, 4, 5, or 6 5 carbon atoms. It is to be understood further that said term "C-C 6 " is to be interpreted as any sub-range comprised therein, e.g. CrC 6 , C 2

C

5 , CrC 4 , CrC 2 , CrC 3 , CrC 4 , CrC 5 CrC 6 ; preferably CrC 2 , CrC 3 , CrC 4 , CrC 5 , CrC 6 ; more preferably C 1

-C

4 . In particular, as used herein, in the case of "alkenyl" or "alkynyl", as used throughout this text, is to be understood as meaning an alkenyl or alkynyl 10 group having a finite number of carbon atoms of 2 to 6, i.e. 2, 3, 4, 5, or 6 carbon atoms. It is to be understood further that said term "C 2

-C

6 " is to be interpreted as any subrange comprised therein, e.g. C 2

-C

8 , C 2

-C

7 , C 2

-C

6 , C 3

-C

5 , C 3

-C

4 , C 2

-C

3 , C 2

-C

4 ,

C

2

C

5 ; preferably C 2

-C

3 . 15 As used herein, the term "CrC4", as used throughout this text, e.g. in the context of the definition of "C-C 4 -alkyl", etc., is to be understood as meaning an alkyl group having a finite number of carbon atoms of 1 to 4, i.e. 1, 2, 3, or 4 carbon atoms. It is to be understood further that said term "CrC4" is to be interpreted as any preferable sub-range comprised therein, e.g. Cr C4, Cr C 3 , Cr C 2 , Cr C3 , C 2

-C

4 . 20 As used herein, the term "C 3

-C

6 ", as used throughout this text, e.g. in the context of the definitions of "C 3

-C

6 -cycloalkyl" or "C 3

-C

6 -heterocycloalkyl", is to be understood as meaning a cycloalkyl group having a finite number of carbon atoms, or a heterocycoalkyl group having a finite number of ring atoms, of 3 to 6, i.e. 3, 25 4, 5, or 6 carbon atoms, preferably 5 or 6 carbon atoms. It is to be understood further that said term "C 3

-C

6 " is to be interpreted as any sub-range comprised therein, e.g. C 3

-C

6 , C 4

-C

5 , C 5

-C

6 ; preferably C 5

-C

6 . Isomers are defined as chemical compounds of the same summation formula but 30 different chemical structure. In general, constitutional isomers and stereoisomers are distinguished.

WO 2006/114334 1 PCT/EP2006/004226 Constitutional isomers have the same summation formula but are distinguished by the way in which their atoms or atom groups are linked. These include functional isomers, position isomers, tautomers or valence isomers. 5 Stereoisomers have basically the same structure (constitutional) - and thus also the same summation formula - but are distinguished by the spatial arrangement of the atoms. In general, configurational isomers and conformational isomers are distinguished. 10 Configurational isomers are stereoisomers that can be converted into one another only by bond breaking. These include enantiomers, diastereomers and E/Z (cis/trans)isomers. Enantiomers are stereoisomers that behave like image and mirror image to one 15 another and do not exhibit any plane of symmetry. All stereoisomers that are not enantiomers are referred to as diastereomers. E/Z (cis/trans)isomers on double bonds are a special case. Conformational isomers are stereoisomers that can be converted into one another 20 by the rotation of single bonds. To delimit types of isomerism from one another, see also the IUPAC Rules, Section E (Pure Appl. Chem. 45, 11-30, 1976). 25 The compounds of general formula I according to the invention also contain the possible tautomeric forms and comprise the E- or Z-isomers or, if a chiral center is present, also the racemates and enantiomers. Among the latter, double-bond isomers are also defined. 30 The compounds according to the invention can also be present in the form of solvates, especially hydrates, whereby the compounds according to the invention consequently contain polar solvents, especially water, as structural elements of the crystal lattice of the compounds according to the invention. The proportion of polar solvent, especially water, can be present in a stoichiometric or else WO 2006/114334 12 PCT/EP2006/004226 unstoichiometric ratio. In the case of stoichiometric solvates and hydrates, hemi-, (semi-), mono-, sesqui-, di-, tri-, tetra-, penta-, etc., solvates or hydrates are also mentioned. 5 If an acid group is included, the physiologically compatible salts of organic and inorganic bases are suitable as salts, such as, for example, the readily soluble alkali and alkaline-earth salts, as well as N-methyl-glucamine, dimethyl-glucamine, ethyl glucamine, lysine, 1,6-hexadiamine, ethanolamine, glucosamine, sarcosine, serinot, tris-hydroxy-methyl-amino-methane, aminopropane diol, Sovak base, and 1-amino 10 2,3,4-butanetriol. If a basic group is included, the physiologically compatible salts of organic and inorganic acids are suitable, such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, citric acid, tartaric acid, succinic acid, methylsulphonic acid, 15 para-toluenesulphonic acid, etc: Those compounds of general formula I in which Q stands for phenyl, A and B, independently of one another, stand for hydrogen, halogen, hydroxy, 20 -NR 3

R

4 , cyano or nitro, or for CI-C 4 -alkyl, C-C 6 -alkoxy or C 3

-C

6 -heterocycloalkyl or with the group -NR 3

R

4 or 25 -CO(NR 3 )-M, whereby the heterocycloalkyl itself optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms, and/or optionally can be interrupted by one or more -C(O)- or -S02 groups in the ring and/or optionally one or more double bonds can be contained in the ring and/or the ring itself optionally can be 30 substituted in one or more places, in the same way or differently, with Cl-C 6 -alkyl, C 3

-C

6 -cycloalkyl, C-C 6 -hydroxyalkyl or with the group -N R 3

R

4 , or for -NR 3 C(0)-L, -NR 3 C(0)-NR 3 -L, -COR 6 , -O-(CH 2 )pR 6 , -CO(NR 3

)-M,

WO 2006/114334 13 PCT/EP2006/004226

-NR

3

(CS)NR

3

R

4 , -NR'SO 2 -M, -S0 2

-NR

3

R

4 , -S0 2

(NR

3 )-M or -0-(CH2)paryl, p stands for an integer of 0, 1, 2, 3, or 4, L stands for C-C 6 -alkyl or C 3

-C

6 -heterocycloalkyl that optionally is substituted in one or more places, in the same way or differently, with 5 C-C 6 -hydroxyalkoxy, C-C 6 -alkoxyalkoxy, C 3

-C

6 -heterocycloalkyl or with the group -NR 3

R

4 , whereby the heterocycloalkyl itself optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms and/or optionally can be interrupted by one or more -C(O)- or -S0 2 groups in the ring 10 and/or optionally one or more double bonds can be contained in the ring and/or the ring itself optionally can be substituted in one or more places, in the same way or differently, with C-C 6 -alkyl, C 3

-C

6 cycloalkyl, C-C 6 -hydroxyalkyl or with the group -NR 3

R

4 , M stands for C-C 6 -alkyl that optionally is substituted in one or more 15 places, in the same way or differently, with the group -NR 3

R

4 or C 3

-C

6 heterocycloalkyl, X stands for -NH- or -NR 5 -, R1 stands for CI-C 4 -alkyl, C 3 -cycloalkyl, allyl or propargyl that optionally is substituted in one or more places, in the same way or differently, 20 with halogen,

R

2 stands for hydrogen or for C-C 6 -alkyl, C-C 6 -alkoxy, CI-C 6 -alkenyl,

C

1

-C

6 -alkynyl, C 3

-C

6 -cycloalkyl, C 3

-C

6 -heterocycloalkyl, aryl or heteroaryl that optionally is substituted in one or more places, in the same way or differently, with halogen, hydroxy, cyano, CI-C 6 -alkyt, 25 C-C 6 -alkoxy, CI-C 6 -hydroxyalkyl, C 3

-C

R

4 , -NR 3 C(0)-L or -NR 3

COOR

7 , whereby the heterocycloalkyl itself optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms and/or optionally 30 can be interrupted by one or more -C(O)- or -S0 2 groups in the ring and/or optionally one or more double bonds can be contained in the ring, and whereby aryl, heteroaryl, C 3

-C

6 -cycloalkyl and/or the C 3

-C

6 heterocycloalkyl ring in each case itself optionally can be substituted WO 2006/114334 14 PCT/EP2006/004226 in one or more places, in the same way or differently, with cyano, halogen, hydroxy, C-C 6 -alkyl, C-C 6 -hydroxyalkyl; C-C 6 -alkoxy, C 3

-C

6 cycloalkyl, C 3

-C

6 -heterocycloalkyl, aryl, benzyl or heteroaryl that optionally is substituted in one or more places, in the same way or 5 differently, with halogen, or for the group -NR 3

R

4 , -NR 3 C(0)-L, -NR 3

(CS)NR

3

R

4 , or

R

2 and R' together form a C 3

-C

6 -heterocycloalkyl ring, which is interrupted at 10 least once by nitrogen and optionally can be interrupted in one or more places by oxygen or sulfur and/or optionally can be interrupted by one or more -C(O)- or -SO 2 - groups in the ring and/or optionally one or more double bonds can be contained in the ring, and/or the ring itself optionally can be substituted in one or more 15 places, in the same way or differently, with cyano, halogen, hydroxy, Cl-C 6 -alkyl, C 3

-C

6 -cycloalkyl, C-C 6 -hydroxyalkyl, CI-C 6 -alkoxyalkyl or with the group -NR 3

R

4 or -COR 6 and/or can be substituted with aryl or heteroaryl that optionally is substituted in one or more places, in the same way or differently, with halogen, C-C 6 -alkoxy or with the group 20

-COR

6 ,

R

3 and R 4 , independently of one another, stand for hydrogen or for C-C 6 -alkyl, Cl-C 6 -alkoxy, -CO-C-C 6 -alkyl or aryl that optionally is substituted in one or more places, in the same way or differently, with halogen, hydroxy, C 3

-C

6 -heterocycloalkyl, C-C 6 -hydroxyalkoxy or with the group 25 -NR 3

R

4 , whereby the heterocycloalkyl itself optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms and/or optionally can be interrupted by one or more -C(O)- or -S02 groups in the ring and/or optionally one or more double bonds can be contained in the ring and whereby the C 3

-C

6 -heterocycloalkyl ring 30 itself in each case optionally can be substituted in one or more places, in the same way or differently, with cyano, halogen, C-C 6 -alkyl, Cl-C 6 -hydroxyalkyl, C-C 6 -alkoxy, C 3

-C

6 -cycloalkyl or with the group

-NR

3

R

4 or -CO-NR 3

R

4 , or WO 2006/114334 15 PCT/EP2006/004226

R

3 and R 4 together form a C 3

-C

6 -heterocycloalkyl ring, which is interrupted at least once by nitrogen and optionally can be interrupted in one or more places by oxygen or sulfur and/or optionally can be interrupted by one or more -C(0)- or -SO 2 - groups in the ring and/or optionally one 5 or more double bonds can be contained in the ring and/or the heterocycloalkyl ring itself optionally can be substituted in one or more places, in the same way or differently, with C-C 6 -alkyl,

C

3

-C

R

4 , 10 R 5 stands for C-C 6 -alkyl, C-C 6 -alkenyl or CI-C 6 -alkynyl that optionally is substituted in one or more places, in the same way or differently, with halogen, hydroxy, cyano, C-C 6 -alkoxy, C 3

-C

6 -cycloalkyl, C 3

-C

6 heterocycloalkyl or with the group -NR 3

R

4 , whereby the heterocycloalkyl itself optionally can be interrupted by one or more 15 nitrogen, oxygen and/or sulfur atoms and/or optionally can be interrupted by one or more -C(0)- or -502- groups in the ring and/or optionally one or more double bonds can be contained in the ring and whereby the C 3

-C

6 -heterocycloalkyl ring itself in each case optionally can be substituted in one or more places, in the same way or 20 differently, with cyano, halogen, C-C 6 -alkyl, C-C 6 -hydroxyalkyl, Cl-C 6 -alkoxy, C 3

-C

6 -cycloalkyl, or with the group -NR 3

R

4 or -CO-NR 3

R

4 , R stands for hydroxy, C-C 6 -alkyl, C-C 6 -alkoxy or the group -NR 3

R

4 , RI stands for -(CH 2 )n-aryl or -(CH 2 )n-heteroaryl, and n stands for an integer of 1, 2, 3, 4, 5 or 6, 25 as well as the solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts thereof, have been shown to be especially effective. Those compounds of general formula 1, in which 30 Q stands for phenyl, A and B, independently of one another, stand for hydrogen, halogen, or for

C-C

4 -alkyl or pyrrolidinyl that optionally is substituted in one or more places, in the same way or differently, with halogen, hydroxy or with the group -NR 3

R

4 or -CO(NR 3

)-M,

WO 2006/114334 16 PCT/EP2006/004226 M stands for C-C 6 -alkyl that optionally is substituted in one or more places, in the same way or differently, with the group -NR 3

R

4 or C 3

-C

6 heterocycloalkyl, X stands for -NH-, 5 R' stands for C-C 4 -alkyl that optionally is substituted in one or more places, in the same way or differently, with halogen, R2 stands for hydrogen or for C-C 6 -alkyl or C 1

-C

6 -alkynyl that optionally is substituted in one or more places, in the same way or differently, with halogen, cyano, or C-C 6 -alkoxy, 10 R 3 and R 4 , independently of one another, stand for hydrogen or for C-C 6 -alkyl, Cl-C 6 -alkoxy, -CO-C-C 6 -alkyl or aryl that optionally is substituted in one or more places, in the same way or differently, with halogen, hydroxy, C 3

-C

6 -heterocycloalkyl, C-C 6 -hydroxyalkoxy or with the group

-NR

3

R

4 , whereby the heterocycloalkyl itself optionally can be 15 interrupted by one or more nitrogen, oxygen and/or sulfur atoms, and/or optionally can be interrupted by one or more -C(O)- or -SO 2 groups in the ring and/or optionally one or more double bonds can be contained in the ring, and whereby the C 3

-C

6 -heterocycloalkyl ring itself optionally can be substituted in one or more places, in the same 20 way or differently, with cyano, halogen, C-C 6 -alkyl, C 1

-C

6 hydroxyalkyl, C-C 6 -alkoxy, C 3

-C

6 -cycloalkyl, or with the group -NR 3

R

4 or -CO-NR 3

R

4 , or

R

3 and R 4 together form a C 3

-C

6 -heterocycloalkyt ring, which is interrupted at 25 least once by nitrogen and optionally can be interrupted in one or more places by oxygen or sulfur and/or optionally can be interrupted by one or more -C(O)- or -SO 2 - groups in the ring and/or optionally one or more double bonds can be contained in the ring, and/or the heterocycloalkyl ring itself optionally can be substituted in 30 one or more places, in the same way or differently, with C-C 6 -alkyl,

C

3

-C

R

4 , and R stands for hydroxy or C-C 6 -alkoxy, WO 2006/114334 17 PCT/EP2006/004226 as well as the solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts thereof, are quite especially effective. 5 Those compounds of general formula 1, in which Q stands for phenyl, A and B, independently of one another, stand for hydrogen, halogen, hydroxy, methoxy or pyrrotidinyl, X stands for -NH-, 10 R' stands for ethyl,

R

2 stands for ethyl or propynyl, as well as the solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts thereof, are extremely effective. 15 A subject of this invention is also the use of the compounds of general formula 1, which may be for the production of a pharmaceutical agent for treating cancer, auto-immune diseases, chemotherapy agent-induced alopecia and mucositis, cardiovascular diseases, infectious diseases, nephrological diseases, chronic and 20 acute neurodegenerative diseases and viral infections. A subject of this invention is also the use of the compounds of general formula I for the production of a pharmaceutical agent for treating cancer, solid tumours and leukemia; auto-immune diseases: psoriasis, alopecia and multiple sclerosis; 25 cardiovascular diseases: stenoses, arterioscleroses, and restenoses; infectious diseases: diseases that are caused by unicellular parasites; nephrological diseases: glomerulonephritis; chronic neurodegenerative diseases: Huntington's disease, amyotrophic lateral sclerosis, Parkinson's disease, AIDS dementia and Alzheimer's disease; acute neurodegenerative diseases: ischemias of the brain and 30 neurotraumas; and viral infections: cytomegalic infections, herpes, hepatitis B and C, and HIV.

WO 2006/114334 18 PCT/EP2006/004226 The compounds according to the invention can be used in the case of cancer, autoimmune diseases, cardiovascular diseases, infectious diseases, nephrological diseases, neurodegenerative diseases and viral infections. 5 The invention also comprises pharmaceutical agents that contain at least one compound of general formula 1. Such pharmaceutical agents are used in the treatment of cancer, autoimmune diseases, cardiovascular diseases, infectious diseases, nephrological diseases, 10 neurodegenerative diseases and viral infections. In general, the compounds according to the invention are mixed in the pharmaceutical agents with suitable formulation substances and vehicles. 15 A subject of this invention is thus also a pharmaceutical preparation for enteral, parenteral and oral administration. To use the compounds of formula I as pharmaceutical agents, the latter are brought into the form of a pharmaceutical preparation, which, in addition to the active 20 ingredient for the enteral or parenteral administration, contains suitable pharmaceutical, organic or inorganic inert carrier materials, such as, for example, water, gelatin, gum Arabic, lactose, starch, magnesium stearate, talc, plant oils, polyalkylene glycols, etc. The pharmaceutical preparations can be present in solid form, for example as tablets, coated tablets, suppositories, or capsules, or in liquid 25 form, for example as solutions, suspensions or emulsions. Moreover, they optionally contain adjuvants such as preservatives, stabilizing agents, wetting agents or emulsifiers, salts for changing the osmotic pressure, or buffers. For parenteral administration, in particular injection solutions or suspensions, in 30 particular aqueous solutions of the active compounds in polyhydroxyethoxylated castor oil, are suitable.

WO 2006/114334 19 PCT/EP2006/004226 As carrier systems, surface-active adjuvants such as salts of bile acids or animal or plant phospholipids, but also mixtures thereof as well as liposomes or components thereof can also be used. 5 For oral administration, in particular tablets, coated tablets or capsules with talc and/or hydrocarbon vehicles or binders, such as, for example, lactose, corn or potato starch, are suitable. The administration can also be done in liquid form, such as, for example, as a juice, to which optionally a sweetener, or, if necessary, one or more flavoring substances, is added. 10 The dosage of the active ingredients can vary depending on the method of administration, age and weight of the patient, type and severity of the disease to be treated and similar factors. The daily dose is 0.5-1,000 mg, preferably 50-200 mg, whereby the dose can be given as a single dose to be administered once or 15 divided into two or more daily doses. The above-described formulations and dispensing forms are also subjects of this invention. 20 In particular, the compounds according to the invention are used as inhibitors of polo-like kinases. Polo-like kinases are defined as in particular Pik 1, Plk 2, Pik 3 and Plk 4.

WO 2006/114334 20 PCT/EP2006/004226 General production diagram for producing the compounds according to the invention. 0 0 S 0 a) O OH RI N R1 N (1) (4) b) d) A B 0 R2 0 S 0PI R R1 N (2) (5) e) c) I A A Q S OH 0O0 ,R2 S X RI N RIR N (3) R1 N General formula I 5 Reaction conditions: a) Saponification in the presence of Pd-tetrakis triphenylphosphine and barbituric acid; b) Condensation with aldehydes; c) Saponification in the presence of Pd-tetrakis-triphenylphosphine and barbituric acid; d) Amide formation from the free carboxylic acid; e) Condensation with aldehydes; f) Amide formation from the free carboxylic acid. 10 WO 2006/114334 21 PCT/EP2006/004226 The production of the compounds of general formula I can be carried out in principle via two alternative synthesis routes. The process variant I comprises the intermediate products 2 and 3 starting from the starting material I that is already described in the International Application WO 03/093249. The process variant II 5 comprises the intermediate products 4 and 5 starting from the same starting material 1. Both process variants are also suitable for use in parallel-synthetic production processes of compounds of general formula 1. Based on the process, the radicals X-R2 or Q of the test compounds according to the invention can be widely varied in the last synthesis stage in each case. 10 In the process variant I, the formation of a by-product 6 was observed in the reaction of the intermediate product 2 to the intermediate product 3. In this connection, in addition to the systematic saponification of the allyl ester functionality, surprisingly enough, an additional decarboxylation takes place. A oA B 0 B Q Sg 0 R0 N 0 j \\ RR N (2) (6) 15 Reaction conditions: g) Saponification in the presence of Pd-tetrakis triphenylphosphine and barbituric acid at elevated temperature.

WO 2006/114334 22 PCT/EP2006/004226 1. Production of the Intermediate Products of Formula (2) According to the Invention Intermediate Product (ZP1) 5 5-[1-(4-Bromo-phenyl)-meth-(Z)-ylidene]-3-ethyl-4-oxo-thiazolidin-(2Z)-ylidene] cyano-acetic acid allyl ester Br 0 0 N N 1.01 g of the starting material (4.0 mmol) that is described in Patent Application 10 PCT/EP2004/012242 A is dissolved in 10 ml of tetrahydrofuran, mixed with 740 mg (4.0 mmol) of p-bromobenzaldehyde and 0.04 ml of piperidine, and stirred for 48 hours at room temperature. The reaction mixture is then concentrated by evaporation almost until the drying is completed and purified without further working-up by crystallization from ethyl acetate. 938 mg (56%) of the title 15 compound is obtained as a pH-dependent (E/Z)-isomer mixture. 1H-NMR (DMSO-d6, stored with K 2

CO

3 , main isomer): 8 = 1.30 (t, 3H); 4.28 (q, 2H); 4.77 (m, 2H); 5.31 (m, 1H); 5.41 (m, 1H); 6.01 (m, 1H); 7.66 (d, 2H); 7.82 (d, 2H); 7.88 (s, 1H) ppm. 20 Similarly produced are also: Table 1: Aldehyde Condensates: WO 2006/114334 23 PCT/EP2006/004226 Ex- Structure and Name of the Main 'H-NMR Molecu ample Isomer tar No. Weight / MS (ESI) [M+1]+ ZP2 N (DMSO-d6, Stored MW: I With K 2 C0 3 , Main 341.39 0> - Isomer): S = MS (ESI) O N \x , N 1. 32 (t, 3 H); [M+1] +: Cyano-[5-[1-(3-cyano-phenyl)-meth-(Z)- 4.28 (q, 2H); 342 ylidene]-3-ethyl-4-oxo-thiazolidin-(2Z)- 4.78 (i, 2H); ylidene]-acetic acid allyl ester 5.30 (dd, 1H); 5.41 (dd, 1 H); 5.9 - 6.1 (n, 1(H); 7.82 (t, 1H); 7.92 (s, 1H); 7.98 (d, 1H); 8.18 (s, 1H) ppm. ZP3 (DMSO-d6, Stored MW: with K 2 C0 3 , Main 341.39 Isomer): S 0 = MS(ESI) -0 N >1.28 (t, 3H); [M+1] +: SN 4.28 (q, 2H); 342 Cyano-[3-ethyl-4-oxo-5-[(E)-3-phenyl- 4.77 (m, 2H); prop-2-en-(Z)-ylidene]-thiazolidin- 5.29 (dd, 1 H); (2Z)-ylidene]-acetic acid allyl ester 5.40 (dd, 1 H); 5.9 - 6.1 ((E, 1H); 7.29 (d, 1H); 7.36-7.48 (m, 5H); 7.63 (d, 1H); WO 2006/114334 24 PCT/EP2006/004226 7.74 (m, 1H) ppm. ZP4 (DMSO-d6, Stored MW: N with K 2

CO

3 , Main 343.41 Isomer): S = MS (ESI) S 1.28 (t, 3H); [M+1] *: N ~2.00 (in, 4H); 344 3.31 (m, 4H); Cyano-[3-ethyl-4-oxo-5-[1 -(4-pyrrol idin-1 -yI-phenyl)-meth-(Z)-ylidene]- 4.26 (q, 2H); thiazolidin-(2Z)-ylidene]-acetic acid 4.77 (m, 2H); allyl ester 5.30 (dd, 1H); 5.41 (dd, 1H); 5.9 - 6.1 (m, 1H); 6.70 (d, 2H); 7.52 (d, 2H); 7.72 (m, 1H) ppm. ZP5 F F (DMSO-d6, Stored F with K 2 C0 3 , Main F Isomer): S 0 6 = N 1.32 (t, 3H); N 4.30 (q, 2H); Cyano-[3-ethyl-5-[1 -(2-fluoro-5-tri- 4.78 (m 2H) fluoromethyl-phenyl)-meth-(Z)-ylidene]- ' ' 4-oxo-thiazolidin-(2Z)-ylidene]-acetic 5.29 (dd, 1H); acid allyl ester 5.41 (dd, 1H); 5.9 - 6.1 (m, 1H); 7.68 (m, 1H); 7.87 (s, 1H); 7.94 - 8.04 (m, 2H) ppm.

WO 2006/114334 25 PCT/EP2006/004226 ZP6 HO 0 (DMSO-d6, Stored with K 2

CO

3 , Main Isomer): s o = 0 N 1 1.32 (t, 3H); N 3.60 (br. s, 1H); 4-[2-[1 -Allyloxycarbonyl-1 -cyano-meth- 4.30 (q, 2H); (Z)-ylidene]-3-ethyl-4-oxo-thiazolidin (5Z)-ylidenemethyl]-benzoic acid 4.78 (m, 2H); 5.30 (dd, 1H); 5.41 (dd, 1H); 5.9 - 6.1 (m, 1H); 7.76 (d, 2H); 7.93 (s, 1H); 8.08 (d, 1H) ppm. ZP7 10 0 (DMSO-d6, Stored with K 2 C0 3 , Main Isomer): s o 8= o N \ 1.36 (t, 3H); N 3.93 (s, 3H); 4-[2-[1-Allyloxycarbonyl-1-cyano-meth- 4.35 (q, 2H); (Z)-ylidene]-3-ethyl-4-oxo-thiazolidin (5Z)-ylidenemethyl]-benzoic acid 4.8 (m, 2H); methyl ester 5.31 (dd, 1H); 5.42 (dd, 1H); 5.9 - 6.1 (m, 1H); 7.82 (d, 2H); 7.92 (s, 1H); 8.12 (d, 1H) ppm.

WO 2006/114334 26 PCT/EP2006/004226 ZP8 H (DMSO-d6, Stored with K 2 C0 3 , Main 0 Isomer): S 0 x 1.30 (t, 3H); 3 \\ Cyano-[3-ethyl-5-[1 -(4-hydroxy-3 methoxy-phenyl)-meth-(Z)-ylidene]- 4.28 (q, 2H); 4-oxo-thiazolidin-(2Z)-ylidene]-acetic acid allyl ester4.8(,2) 5.29 (dd, 1H); 5.41 (dd, 1H); 5.9- 6.1 ( , 1H); 6.98 (d, 1H); 7.22 (dd, 2H); 7.32 (d, 1H); 7.82 (s, 1H) ppm. ZP9 0 (DMSO-d6, Stored 0 with K 2

CO

3 , Main Isomer): s o = 0 N> \1.34 (t, 3H); N 3.86 (s, 3H); Cyano-[5-[1-(3,4-dimethoxy-phenyl)- 3.90 (s, 3H); meth-(Z)-ylidene]-3-ethyl-4-oxo-thiazo lidin-(2Z)-ylidene]-acetic acid allyl ester 4.34 (q, 2H); 4.79 (m, 2H); 5.29 (dd, 1H); 5.42 (dd, 1H); 5.9 - 6.1 (m, 1H); 7.20 (d, 2H); 7.31 (s, 1H); 7.32 (d, 1H); 7.83 (s, 1H) ppm.

WO 2006/114334 27 PCT/EP2006/004226 ZPIO HO (DMSO-d6, Stored with K 2

CO

3 , Main s o Isomer): 0 N N 1.29 (t, 3H); Cyano-[3-ethyl-5-[1-(3-hydroxy-phenyl)- 4.28 (q, 2H); meth-(Z)-ylidene]-4-oxo-thiazolidin-(2Z) ylidene]-acetic acid allyl ester 4.78 (m, 2H); 5.30 (dd, 1H); 5.41 (dd, 1H); 5.9 - 6.1 (m, 1H); 6.93 (dd, 1H); 7.09 (m, 2H); 7.14 (d, 1H); 7.38 (dd, 1H); 7.79 (s, 1H); 9.8 - 10.1 (br. s, 1H) ppm. ZP11 (DMSO-d6, Stored HO with K 2

CO

3 , Main 0 s o Isomer): 0 N \ N 1.31 (t, 3H); [5-[1 -(2-Carboxymethoxy-phenyl)-meth- 4.28 (q, 2H); (Z)-ylidene]-3-ethyl-4-oxo-thiazolidin (2Z)-ylidene]-cyano-acetic acid allyl ester 4.72 (s, 2H); 4.76 (m, 2H); 5.28 (dd, 1H); 5.39 (dd, 1H); 5.9 - 6.1 (m, 1H); 7.04 (d, 1H); 7.16 (m, 1H); 7.48 (m, 1H); 7.55 (d, 1H); 8.17 (s, 1H) ppm.

WO 2006/114334 28 PCT/EP2006/004226 ZPI2 F (DMSO-d6, Stored with K 2

CO

3 , Main Isomer): S 0 6 N 1.30 (t, 3H); Cyano-[3-ethyl-5-[1 -(4-fluoro-phenyl)- 4.29 (q, 2H); meth-(Z)-ylidene]-4-oxo-thiazolidin- 4.77 (m, 2H); (2Z)-ylidene]-acetic acid allyl ester 5.29 (dd, 1H); 5.41 (dd, 1H); 5.9 - 6.1 (m, 1H); 7.45 (m, 2H); 7.78 (m, 2H); 7.92 (s, 1H) ppm. ZPI3 0 (DMSO-d6, Stored ON with K 2

CO

3 , Main 0 Isomer): S 0 6= N o N 1.32 (t, 3H); 4.31 (q, 2H); Cyano-[3-ethyl-5-[1-(3-nitro-phenyl)- 4.79 (m 2H) meth-(Z)-ylidene]-4-oxo-thiazolidin- ' ' ' (2Z)-ylidene]-acetic acid allyl ester 5.30 (dd, 1 H); 5.41 (dd, 1H); 5.9 - 6.1 (m, 1H); 7.90 (m, 1H); 8.07 (s, 1H); 8.12 (d, 1H); 8.34 (m, 1H); 8.56 (m, 1H) ppm.

WO 2006/114334 29 PCT/EP2006/004226 2. Production of the Intermediate Products of the Formula According to the Invention Intermediate Product (ZP14) 5 Cyano-[3-ethyl-4-oxo-5-[1-(4-pyrrolidin-1-yl-phenyl)-meth-(Z)-ylidene]-thiazolidin (2Z)-yidene] -acetic Acid 0K 00 o 0 S OH N 0 10 1.0 g (about 2.44 mmol) of cyano-[3-ethyl-4-oxo-5-[1-(4-pyrrolidin-1-yl-phenyl) meth-(Z)-ylidene]-thiazolidin-(2Z)-ylidene]-acetic acid allyl ester is stirred together with 341 mg (2.66 mmol) of barbituric acid and 277 mg (0.24 mmot) of palladium tetrakis-triphenylphosphine in 10 ml of tetrahydrofuran for 24 hours at room temperature. For working-up, the crude product is mixed with ethyl acetate, and 15 the precipitate that is formed is suctioned off. The thus isolated product (648 mg, 71%) is used without further purification in the next steps. 1H-NMR (DMSO-d6, stored with K 2

CO

3 , main isomer): 5 = 1.25 (t, 3H); 1.97 (m, 4H); 3.38 (m, 4H); 4.27 (q, 2H); 6.72 (m, 2H), 7. 5-7.65 (m, 2H), 7.71 (s, 1H) ppm. 20 WO 2006/114334 30 PCT/EP2006/004226 Production of the Intermediate Products of Formulae (4) and (5) According to Process Variant || ZP1 5 2-Cyano-2- [3-ethyl-4-oxo-3-yl-meth-(Z)-ylidene] -thiazolidin-(2Z)-ylidene] -acetic 5 acid 0 ____ ___S OH 0 N O O N O NN 40 g (about 0.16 mol) of the allyl ester already described in Patent Application WO 03/093249 is stirred together with 22.18 g (- 0.17 mmol) of barbituric acid and 18.3 10 g (10 mol%) of palladium-tetrakis-triphenylphosphine in 50 ml of THF over a period of 72 hours at room temperature. After TLC monitoring of the reaction mixture, the solvent is removed in a vacuum. The crude product is used without further purification in the subsequent reactions and contains about 50% of the desired carboxylic acid. 15 An analytically pure sample was obtained by filtration and subsequent boiling-off of the filter cake with toluene. 1H-NMR (DMSO-d6, stored with K 2

CO

3 , main isomer): 5 = 1.20 (t, 3H); 3.60 (s, 2H); 20 4.12 (q, 2H); 11.1 (s, 1H) ppm.

WO 2006/114334 31 PCT/EP2006/004226 ZP16 2-Cyano-2- [3-ethyl-4-oxo-3-yl-meth- (Z)-ylidene] -thiazotidin- (2Z)-ylidene] -N-ethyl acetamide oI S O H 0 N 5 15 g of the crude product 2-cyano-2-[3-ethyl-4-oxo-3-yl-meth-(Z)-ylidene] thiazolidin-(2Z)-ylidene]-acetic acid is introduced together with 21.2 ml of ethylamine and 11.8 g of sodium bicarbonate into 200 ml of DMF. After 30 minutes 10 of stirring at room temperature, 13.8 g of TBTU is added, and the reaction mixture is further stirred overnight at room temperature. For working-up, the crude product is mixed with ethyl acetate. The aqueous phase is extracted twice more with 100 ml each of ethyl acetate. The combined organic phases are extracted in succession with saturated sodium bicarbonate solution and saturated sodium chloride solution. 15 Then, the organic phase is dried on sodium sulfate, filtered, and concentrated by evaporation. By crystallization from ethanol, 4.05 g (48% relative to the indicated content of 2 cyano-2-[3-ethyl-4-oxo-3-yt-meth-(Z)-ylidene]-thiazolidin-(2Z)-ytidene]-acetic acid 20 in the crude product) of the desired product is isolated from the crude product. 1H-NMR (DMSO-d6, stored with K 2

CO

3 , main isomer): 5 = 1.00 (t, 3H); 1.16 (t, 3H); 3.14 (m, 2H); 3.77 (s, 2H); 4.05 (q, 2H); 7.74 (m, 1H) ppm.

32 WO 2006/114334 PCT/EP2006/004226 Similarly produced are also: Table 3a: Amides : Ex- Structure and Name 'H-NMR Molecu ample tar No. Weight/ MS (ESI) [M+1]* ZP1 7 F (DMSO-d6, Stored N F with K 2

CO

3 ): O IN \H N 1.17 (t, 3H); 2-Cyano-2-[3-ethyl-4-oxo-3-yI-meth-(Z)- 3.03 (m, 2H); ylidene]-thiazolidin-(2Z)-ylidene]-N (2,2-difluorethyl)-acetamide 3.78 (s, 2H), 4.07 (q, 2H); 6.02 (m, 1H); 8.01 (m, 1H) ppm. ZP1 8 0 (DMSO-d6, Stored H with K 2

CO

3 ): 5 = 2-Cyano-2-[3-ethyl-4-oxo-3-yI-meth- (t, H); (Z)-ylidene]-thiazolidin-(2Z)-ylidene]- 3.03 (m, 1 H); N-prop-2-ynyl-acetamide 3.79 (s, 2H); 3.86 (m, 2H); 4.06 (q, 2H); 8.18 (m, 1H) ppm. ZP19 0 /--=N (DMSO-d6, Stored S N IN H with K 2

CO

3 ): N 2-Cyano-N-cyanomethyl-2-[3-ethyl- 1.35 (t, 3H); 4-oxo-thiazolidin-(2Z)-ylidene]- 3.70 (s, 2H); acetamide WO 2006/114334 33 PCT/EP2006/004226 4.24 (m, 4H); 6.67 (m, 1 H) ppm. 3. Production of the End Products According to the Invention 5 Example 1 2-Cyano-N-ethyl-2-[3-ethyl-4-oxo-5-[1-(4-pyrrolidin-1 -yl-phenyl)-meth-(Z)-ylidene] thiazolidin-(2Z)-ylidene]-acetamide 10 __ _ __ _ _ S 10 50 mg (0.14 mmol) of cyano-[3-ethyl-4-oxo-5-[1-(4-pyrrolidin-1-yl-phenyl)-meth-(Z) ylidene]-thiazolidin-(2Z)-ylidene]-acetic acid is introduced together with 0.2 ml (0.41 mmol) of ethylamine (2 M in THF) and 154 mg (0.41 mmol) of HATU in 10 ml of DMF, and it is stirred overnight at room temperature. For working-up, the crude 15 product is mixed with ethyl acetate and extracted 3 times with 10 ml each of water. The combined organic phases are dried on sodium sulfate, filtered and concentrated by evaporation. The purification of the crude product is carried out by column chromatography on silica gel. 32 mg (60%) of a yellow solid is isolated. 20 As an alternative to the production of aides via the free carboxylic acids, the corresponding compound can also be produced by condensation of the corresponding aides with aldehydes : WO 2006/114334 34 PCT/EP2006/004226 N 0 0O' S N N H + 0 N, O o NN 50 mg (0.21 mmol) of 2-cyano-2-[3-ethyl-4-oxo-3-yl-meth-(Z)-ylidene]-thiazolidin (2Z)-ylidene]-N-ethyl-acetamide is stirred together with 53 mg (0.30 mmol) of 4 5 pyrrolidin-1-yl-benzaldehyde and 10 pl of piperidine in 10 ml of THF at room temperature overnight. After the reaction is completed, the desired product is filtered off; the filtrate is discarded. 54 mg (70%) of a yellow solid is isolated. As an alternative to this, the isolation of the desired product can be carried out by aqueous working-up with ethyl acetate, drying on sodium sulfate and subsequent 10 purification of the crude product by column chromatography on silica gel. 1H-NMR (DMSO-d6, stored with K 2 C0 3 , main isomer; measurement made at 350 K): S = 1.13 (t, 3H); 1.29 (t, 3H); 2.02 (m, 4H); 3.25 (q, 2H); 3.36 (m, 4H); 4.29 (q, 2H); 6.72 (d, 2H); 7.52 (d, 2H); 7.57 (s, 1H); 7.62 (s, 1H) ppm. 15 Similarly produced are also: Table 3: Amides: WO 2006/114334 35 PCT/EP2006/004226 Ex- Structure and Name 'H-NMR Molecu ample tar No. Weight / MS (ESI) [M+1]* 2 HO (DMSO-d6, Stored MW: I with K 2 C0 3 , Main 343.41 S N Isomer): 2 HO SN 6= MS O) N X , N 1.05 (t, 3H); (ES+) 2-Cyano-N-ethyl-2-[3-ethyl-S-[1-(3- 1.5(,1H;[+]+ hydroxy-phenyl)-meth-(Z)-ylidene] 4-oxo-thiazolidin-(2Z)-ylidene] acetamide 4.22 (q, 2H); 6.85 (i, 1 H); 7.06 (s, 1 H); 7.09 (t, 1H); 7.34 (m, 1H); 7.63 (s, 1H); 8.06 (s, 1H); 9.9 (s, br, 1H) ppm. 3 OH (DMSO-d6, Stored MW: with K 2 C0 3 , Main 343.41 0 Isomer): O N K 1.04 (t, 3H); (ES+) 1.23 (t, 1H); [M+1] N: 2-Cyano-N-ethyl-2-[3-ethyl-5-[1-(4 hydroxy-phenyl)-meth-(Z)-ylidene]- 3.17 (i, 2H); 344 4-oxo-thiazolidin-(2Z)-ylidene]- 4.21 (q, 2H); acetamide 6.82 (t, 2H); 6.98 (m, 2H); 7.11 (s, 1H); WO 2006/114334 36 PCT/EP2006/004226 7.93 (m, 1 H) ppm. 4 Br (DMSO-d6, Stored MW: with K 2 C0 3 , Main 406.30 0 Isomer): S N - H 8MS 0 N1.04 (t, 3H); (ES+) 1. 26 (t, 1 H); [M+1 ] +: 2-[5-[1-(4-Bromo-phenyl)-meth-(Z) ylidene]-3-ethyl-4-oxo-thiazolidin (2Z)-ylidene]-2-cyano-N-ethyl- 4.23 (q, 2H); 8 acetamide 7.61 (in, 2H); 7.69 (s, 1 H); 7.76 (in, 2H); 8.08 (in, 1 H) ppm. 5 OH (DMSO-d6, Stored MW: with K 2

CO

3 , Main 373.43 0 Isomer): S N - H MS 0 N 1.04 (t, 3H); (ES+) 1.26 (t, 1H); [M+1] +: 2-Cyano-N-ethyl-2-[3-ethyl-5-[1-(4- 3.18 (m, 2H); 374 hydroxy-3-methoxy-phenyl)-meth-(Z) ylidene4-4-oxo-thiazolidin-(2Z)-ylidene]- 3.76 (s, 3H); acetamide 4.21 (q, 2H); 6.73 (s, 1H); 7.1 (m, 2H); 7.60 (s, 1 H); 7.85 (m, 1H) ppm.

WO 2006/114334 37 PCT/EP2006/004226 6 (DMSO-d6, Stored MW: with

K

2 C0 3 , Main 357.43 S N Isomer): - H N NM 0 \, N 1 .05 (t, 3H); (ES+) 2-Cyano-N-ethyl-2-[3-ethyl-5-[1-(3- 1 27 (t, 1 H); [M+1 methoxy-phenyl)-meth-(Z)-ylidene] 4-oxo-thiazolidin-(2Z)-ylidene]-acet 3.19 (i, 2H); 358 3.78 (s, 3H); 4.23 (q, 2H); 7.05 (t, 1H); 7.2 (t, 2H); 7.48 (m, 1H); 7.70 (s, 1H); 8.04 (m, 1H) ppm. 7 HO (DMSO-d6, Stored MW: 0 with K 2 C0 3 , Main 343.41 s N Isomer): - H o N MS \, N 1. 27 (t, 1 H); (ES+) 2-Cyano-2-[3-ethyl-5-[1-(3-hydroxy- 3.05 (i, 1 H); [M+1 +: phenyl)-meth-(Z)-ylidene]-4-oxo thiazolidin-(2Z)-ylidene]-N-prop-2 ynyl-acetamide 4.23 (q, 2H); 6.86 (in, 1 H); 7.06 (s, 1H); 7.08 (m, 1H); 7.32 (m, 1H); 7.63 (s, 1H); 8.43 (m, 1H); 9.9 (s, br, 1H) ppm.

WO 2006/114334 38 PCT/EP2006/004226 8 OH (DMSO-d6, Stored MW: with K 2 C0 3 , Main 353.41 0 Isomer): S N O N, .2 t ) E+ N 3.06 (in, 1 H); [M+1] +: 2-Cyano-2-[3-ethyl-5-[1-(4-hydroxy- 3.88 (i, 2H); 354 phenyl)-meth-(Z)-ylidene]-4-oxo thiazolidin-(2Z)-ylidene]-N-prop-2- 4.23 (q, 2H); ynyl-acetamide 6.93 (i, 2H); 7.54 (t, 2H); 7.68 (s, 1H); 8.48 (m, 1H); 10.4 (s, br, 1H) ppm. 9 OH (DMSO-d6, Stored with K 2 C0 3 , Main _- Isomer): S N xH N 1.25 (t, 1H); 3.07 (m, 1H); 2-Cyano-2-[3-ethyl-5-[1-(4-hydroxy- 3.80 (s, 3 H); 3-methoxy-phenyl)-meth-(Z)-ylidene] 4-oxo-thiazolidin-(2Z)-ylidene]-N- 3.89 (m, 2H); prop-2-ynyl-acetamide 4.23 (q, 2H); 6.96 (m, 1H); 7.16 (m, 1H); 7.27 (m, 1H); 7.69 (s, 1H); 8.38 (m, 1H); 9.9 (s, br, 1H) ppm.

WO 2006/114334 39 PCT/EP2006/004226 10 (DMSO-d6, Stored N with K 2

CO

3 , Main Isomer): o , =6= S N H 1.23 (t, 1 H); N 1.92 (m, 4H); 2-Cyano-2-[3-ethyl-4-oxo-5-[1 -(4-pyrrolidin- 3.05 (m, 1 H); I -yI-phenyl)-meth-(Z)-ylidene]-thiazolidin (2Z)-ylidene]-N-prop-2-ynyl-acetamide 3.29 (m, 4H); 3.89 (m, 2H); 4.22 (q, 2H); 6.68 (d, 2H); 7.45 - 7.60 (m, 3H); 8.29 (m, 1H) ppm. 11 0- (DMSO-d6, Stored 1+ O.N with K 2

CO

3 , Main - _Isomer): S N - H 0 N 1.28 (t, 1H); N 3.08 (m, 1H); 2-Cyano-2-[3-ethyl-5-[1 -(3-nitro-phenyl) meth-(Z)-ylidene]-4-oxo-thiazolidin-(2Z)- 3.92 (m, 2H); ylidene]-N-prop-2-ynyl-acetamide 4.23 (q, 2H); 6.68 (d, 2H); 7.85 (t, 1H); 7.90 (s, 1H); 8.07 (m, 1H); 8.28 (m, 1H); 8.52 (m, 2H) ppm.

WO 2006/114334 40 PCT/EP2006/004226 12 OH (DMSQ-d6, Stored MW: with

K

2 C0 3 , Main 387.46 S N Isomer): o N OH MS(ES-) XN N1. 21 (t, 3 H); [M-1]: 2-Cyano-2-[3-ethyl-5-[1-(3-hydroxy- 1.28 (s, 6H); 386 phenyl)-meth-(Z)-ylidene]-4-oxo thiazolidin-(2Z)-ylidene]-N-(2-hydroxy- 3.35 (i, 2H); 1,1 -dimethyl-ethyl)-acetamide 4.20 (q, 2H); 5.19 (t, 1H); 6.86 (m, 1H); 6.91 (s, 1H); 7.04 (t, 1H); 7.08 (in, 1H); 7.08 (, 1H); 7.32 (t, 1H); 7.62 (s, 1 H); 9.93 (s, 1H) ppm. 13 (DMSO-d6, Stored MW: 0 INwith K 2 C0 3 , Main 401.49 0 H Isomer): S N

-

6 MS N; \\ -OH 0 N 1.21 - 1.30 (in, (ES+) 9H); 2-Cyano-2-[3-ethyl-5-[1-(3-methoxy phenyl)-meth-(Z)-ylidene]-4-oxo-thiaz- 3.34 (i, 2H); 402 olidin-(2Z)-ylidene]-N-(2-hydroxy-1, 1 dimethyl-ethyl)-acetamide , 4.21 (q, 2 H); 5.20 (t, 1 H); 6.94 (s, 1H); 7.08 (s, 1H); 7.23 (q, 2H); 7.49 (t, 1H); 7.71 (m, 1H) ppm.

WO 2006/114334 41 PCT/EP2006/004226 14 0-(DMSO-d6, Stored MW: 14 1 O~,Nwith K 2 C0 3 , Main 416.46 0 N OH 1.23-1.30(m, [M-1] N9H); 415 2-Cyano-2-[3-ethy-5-[1 -(3-nitro-phenyl)- 3.34 (m, 2H); meth-(Z)-ylidene]-4-oxo-thiazolidin-(2Z) ylidene]-N-(2-hydroxy-1,1 -dimethyl-ethyl)- 4.22 (q, 2H); acetamide 5.21 (t, 1 H); 6.97 (s, M H); 7.85 (t, 1H); 8.07 (m, 1H); 8.28 (t, 1H); 8.52 (m, 1H) ppm. Examples 5 The following examples describe the biological action of the compounds according to the invention without the action of the compounds being limited to these examples : PLK Enzyme Assay 10 Recombinant human Plk-1 (6xHis) was purified from baculovirus-infected insect cells (Hi5). 10 ng of (produced in a recombinant manner and purified) PLK enzyme is incubated 15 for 90 minutes at room temperature with biotinylated casein and 33P-y-ATP as a substrate in a volume of 15 pl in 384-wetl Greiner small-volume microtiter plates (final concentrations in the buffer: 660 ng/ml of PLK; 0.7 pmol of casein, 0.5 pmol of ATP incl. 400 nCi/ml of 33P-y-ATP; 10 mmol of MgCl2, 1 mmol of MnCI2; 0.01% NP40; 1 mmol of DTT, protease inhibitors; 0.1 mmol of Na2VO3 in 50 mmol of 20 HEPES, pH 7.5). To complete the reaction, 5 pl of stop solution (500 pmot of ATP; WO 2006/114334 42 PCT/EP2006/004226 500 mmol of EDTA; 1% Triton XIOO; 100 mg/ml of streptavidin-coated SPA beads in PBS) is added. After the microtiter plate is sealed by film, the beads are sedimented by centrifuging (10 minutes, 1500 rpm). The incorporation of 33P-y ATP in casein is intended as a measurement of enzyme activity by B-counting. The 5 extent of the inhibitor activity is referenced against a solvent control (= uninhibited enzyme activity = 0% inhibition) and the mean value of several batches that contained 300 pmol of wortmannin (= completely inhibited enzyme activity = 100% inhibition). 10 Test substances are used in various concentrations (0 pmol, as well as in the range of 0.01 - 30 pmol). The final concentration of the solvent dimethyl sulfoxide is 1.5% in all batches. Proliferation Assay 15 Cultivated human MaTu breast tumour cells were flattened out at a density of 5000 cells/measuring point in a 96-well multititer plate in 200 pt of the corresponding growth medium. After 24 hours, the cells of one plate (zero-point plate) were colored with crystal violet (see below), white the medium of the other plates was 20 replaced by fresh culture medium (200 pl), to which the test substances were added at various concentrations (0 pm, as well as in the range of 0.01-30 pm; the final concentration of the solvent dimethyl sutfoxide was 0.5%). The cells were incubated for 4 days in the presence of test substances. The cell proliferation was determined by coloring the cells with crystal violet: the cells were fixed by adding 25 20 p/measuring point of an 11% glutaric aldehyde solution for 15 minutes at room temperature. After three washing cycles of the fixed cells with water, the plates were dried at room temperature. The cells were colored by adding 100 pl/measuring point of a 0.1% crystal violet solution (pH was set at 3 by adding acetic acid). After three washing cycles of the colored cells with water, the plates 30 were dried at room temperature. The dye was dissolved by adding 100 pl/measuring point of a 10% acetic acid solution. The extinction was determined by photometry at a wavelength of 595 nm. The change of cell growth, in percent, was WO 2006/114334 43 PCT/EP2006/004226 calculated by standardization of the measured values to the extinction values of the zero-point plate (=0%) and the extinction of the untreated (0 pm) cells (=100%). Table 1: Assay Data 5 Example Structure PLK-1 Inhibition of No. IC50 [nM] the Tumour Inhibition Cell Proliferation (MaTu) IC50 [pM] 10 23 Not N Determined O S N o N \ N 3 OH 230 Not Determined O , S N N 8 OH 39 3.2 S N o N \ N It thus can be seen from Table 1 that the compounds of general formula (I) exhibit nanomolar inhibition both on the enzyme and in the proliferation test.

Claims

1. A compound of general formula I : A 0 Q -S N X-R

2 B N CN 5 0 \ R ( I ), in which 10 Q stands for aryt, A and B, independently of one another, stand for hydrogen, halogen, hydroxy, -NR 3 R 4 , cyano or nitro, or for C 1 -C 4 -alkyl, C 1 -C 6 -alkoxy or C 3 -C-heterocycloalkyl that optionally is 15 substituted in one or more places, in the same way or differently, with halogen, hydroxy, C 3 -C-heterocycloalkyt or with the group -NR 3 R 4 or -CO(NR 3 )-M, whereby the heterocycloalkyl itself optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms and/or optionally can be interrupted by one or more -C(O)- or -SO 2 20 groups in the ring and/or optionally one or more double bonds can be contained in the ring and/or the ring itself optionally can be substituted in one or more places, in the same way or differently, with C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C1-C 6 -hydroxyalkyt or with the group -NR 3 R 4 , 25 or for -NR 3 C(0)-L, -NR 3 C(O)-NR 3 -L, -COR 6 , -O-(CH2)pR 6 , -CO(NR 3 )-M, -NR 3 (CS)NR 3 R 4 , -NR 3 SO 2 -M, -S0 2 -NR 3 R 4 , - SO 2 (NR 3 )-M or -O-(CH 2 )paryl, p stands for an integer of 0, 1, 2, 3, or 4, L stands for C 1 -C 6 -alkyl or C 3 -C-heterocycloalkyl that optionally is 30 substituted in one or more places, in the same way or differently, with WO 2006/114334 45 PCT/EP2006/004226 Cl-C 6 -hydroxyalkoxy, C-C 6 -alkoxyalkoxy, C 3 -C 6 -heterocycloalkyl or with the group -NR 3 R 4 , whereby the heterocycloalkyl itself optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms and/or optionally can be interrupted by one or more -C(O)- or 5 -So 2 - groups in the ring and/or optionally one or more double bonds can be contained in the ring, and/or the ring itself optionally can be substituted in one or more places, in the same way or differently, with Cl-C 6 -alkyl, C 3 -C 6 -cycloalkyl, C-C 6 -hydroxyalkyl or with the group -NR 3 R 4 , 10 M stands for C-C 6 -alkyl that optionally is substituted in one or more places, in the same way or differently, with the group -NR 3 R 4 or C 3 -C 6 heterocycloalkyt, X stands for -NH- or -NR 5 -, R1 stands for C-C 4 -alkyl, C 3 -cycloalkyl, allyl or propargyl that optionally 15 is substituted in one or more places, in the same way or differently, with halogen, R 2 stands for hydrogen or for C-C 6 -alkyl, C-C 6 -alkoxy, C-C 6 -alkenyl, Cl-C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -heterocycloalkyl, aryl or heteroaryl that optionally is substituted in one or more places, in the 20 same way or differently, with halogen, hydroxy, cyano, C-C 6 -alkyl, CI-C 6 -alkoxy, C-C 6 -hydroxyalkyl, C 3 -C 6 -cycloalkyl, CrC6 heterocycloalkyl, C-C 6 -alkynyl, aryl, aryloxy, heteroaryl or with the group -S-C-C 6 -alkyl, -COR 6 , -NR 3 R 4 , -NR 3 C(0)-L or -NR 3 COOR 7 , whereby the heterocycloalkyl itself optionally can be interrupted by 25 one or more nitrogen, oxygen and/or sulfur atoms and/or optionally can be interrupted by one or more -C(O)- or -SO 2 groups in the ring and/or optionally one or more double bonds can be contained in the ring, and whereby aryl, heteroaryl, C 3 -C 6 -cycloalkyl- and/or the C 3 -C 6 30 heterocycloalkyl ring in each case itself optionally can be substituted in one or more places, in the same way or differently, with cyano, halogen, hydroxy, C-C 6 -alkyl, C-C 6 -hydroxyalkyl, or C-C 6 -alkoxy, C 3 -C 6 -cycloalkyl, C 3 -C 6 -heterocycloalkyl, aryl, benzyl or heteroaryl WO 2006/114334 46 PCT/EP2006/004226 that optionally is substituted in one or more places, in the same way or differently, with halogen, or for the group -NR 3 R 4 , -NR 3 C(O)-L, or -NR 3 (CS)NR 3 R 4 , 5 or R 2 and R' together form a C 3 -C 6 -heterocycloalkyl ring, which is interrupted at least once by nitrogen and optionally can be interrupted in one or more places by oxygen or sulfur and/or optionally can be interrupted by one or more -C(O)- or -SO 2 - groups in the ring and/or optionally one 10 or more double bonds can be contained in the ring, and/or the ring itself optionally can be substituted in one or more places, in the same way or differently, with cyano, halogen, hydroxy, C,-C 6 -alkyl, C 3 -C 6 -cycloalkyl, Cl-C 6 -hydroxyalkyl, C-C 6 -alkoxyalkyl or with the group -NR 3 R 4 or -COR 6 , 15 and/or can be substituted with aryl or heteroaryl that optionally is substituted in one or more places, in the same way or differently, with halogen, C-C 6 -alkoxy or with the group -COR , R 3 and R 4 , independently of one another, stand for hydrogen or for C-C 6 -alkyl, Cl-C 6 -alkoxy, -CO-C-C 6 -alkyl or aryl that optionally is substituted in 20 one or more places, in the same way or differently, with halogen, hydroxy, C 3 -C 6 -heterocycloalkyl, C-C 6 -hydroxyalkoxy or with the group -NR 3 R 4 , whereby the heterocycloalkyl itself optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms and/or optionally can be interrupted by one or more -C(O)- or -SO 2 25 groups in the ring and/or optionally one or more double bonds can be contained in the ring, and whereby the C 3 -C 6 -heterocycloalkyl ring itself optionally can be substituted in one or more places, in the same way or differently, with cyano, halogen, C-C 6 -alkyl, C-C 6 hydroxyalkyl, C-C 6 -alkoxy, C 3 -C 6 -cycloalkyl, or with the group -NR 3 R 4 30 or -CO-NR 3 R 4 , or R 3 and R 4 together form a C 3 -C 6 -heterocycloalkyl ring, which is interrupted at least once by nitrogen and optionally can be interrupted in one or more places by oxygen or sulfur and/or optionally can be interrupted WO 2006/114334 47 PCT/EP2006/004226 by one or more -C(0)- or -502- groups in the ring and/or optionally one or more double bonds can be contained in the ring, and/or the heterocycloalkyl ring itself optionally can be substituted in one or more places, in the same way or differently, with C-C 6 -alkyl, 5 C 3 -C 6 -cycloalkyl, C-C 6 -hydroxyalkyl, C-C 6 -alkoxyalkyl, cyano, hydroxy or with the group -NR 3 R 4 , R 5 stands for C-C 6 -alkyl, C-C 6 -alkenyl, or CI-C 6 -alkynyl that optionally is substituted in one or more places, in the same way or differently, with halogen, hydroxy, cyano, C-C 6 -alkoxy, C 3 -C 6 -cycloalkyl, C 3 -C 6 10 heterocycloalkyl, or with the group -NR 3 R 4 , whereby the heterocycloalkyl itself optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms and/or optionally can be interrupted by one or more -C(0)- or -SO 2 groups in the ring and/or optionally one or more double bonds can be contained in the ring, and 15 whereby the C 3 -C 6 -heterocycloalkyl ring itself in each case optionally can be substituted in one or more places, in the same way or differently, with cyano, halogen, C-C 6 -alkyl, C-C 6 -hydroxyalkyl, Cl-C 6 -alkoxy, C 3 -C 6 -cycloalkyl, or with the group -NR 3 R 4 or -CO-NR 3 R 4 , R stands for hydroxy, C-C 6 -alkyl, C-C 6 -alkoxy or the group -NR 3 R 4 , 20 R' stands for -(CH 2 )n-aryl or -(CH 2 )n-heteroaryl, and n stands for an integer of 1, 2, 3, 4, 5 or 6, as well as the solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts thereof. 25 2. The compound of general formula I according to claim 1, in which Q stands for phenyl, A and B, independently of one another, stand for hydrogen, halogen, hydroxy, -NR 3 R 4 , cyano or nitro, or 30 for C-C 4 -alkyl, C-C 6 -alkoxy or C 3 -C 6 -heterocycloalkyl that optionally is substituted in one or more places, in the same way or differently, with halogen, hydroxy, C 3 -C 6 -heterocycloalkyl or with the group -NR 3 R 4 or -CO(NR 3 )-M, whereby the heterocycloalkyl itself optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms, WO 2006/114334 48 PCT/EP2006/004226 and/or optionally can be interrupted by one or more -C(0)- or -502 groups in the ring and/or optionally one or more double bonds can be contained in the ring and/or the ring itself optionally can be substituted in one or more places, in the same way or differently, with 5 C-C 6 -alkyl, C 3 -C 6 -cycloalkyl, C-C 6 -hydroxyalky or with the group -NR 3 R 4 , or for -NR 3 C(0)-L, -NR 3 C(0)-NR 3 -L, -COR 6 , -0-(CH 2 )pR 6 , -CO(NR 3 )-M, -NR 3 (CS)NR 3 R 4 , -NR 3 SO 2 -M, -S0 2 -NR 3 R 4 , -S0 2 (NR 3 )-M or -O-(CH 2 )paryl, 10 p stands for an integer of 0, 1, 2, 3, or4, L stands for C-C 6 -alkyl or C 3 -C 6 -heterocycloalkyl that optionally is substituted in one or more places, in the same way or differently, with C 1 -C 6 -hydroxyalkoxy, C-C 6 -alkoxyalkoxy, C 3 -C 6 -heterocycloalkyl or with the group -NR 3 R 4 , 15 whereby the heterocycloalkyl itself optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms and/or optionally can be interrupted by one or more -C(0)- or -502 groups in the ring and/or optionally one or more double bonds can be contained in the ring and/or the ring itself optionally can be substituted in one or more 20 places, in the same way or differently, with C-C 6 -alkyl, C 3 -C 6 cycloalkyl, CI-C 6 -hydroxyalkyl or with the group -NR 3 R 4 , M stands for C-C 6 -alkyt that optionally is substituted in one or more places, in the same way or differently, with the group -NR 3 R 4 or C 3 -C 6 heterocycloalkyl, 25 X stands for -NH- or -NR 5 R1 stands for C-C 4 -alkyl, C 3 -cycloalkyl, allyl or propargyl that optionally is substituted in one or more places, in the same way or differently, with halogen, R 2 stands for hydrogen or for C-C 6 -alkyl, C-C 6 -alkoxy, C-C 6 -alkenyl, 30 C-C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -heterocycloalkyt, aryl or heteroaryl that optionally is substituted in one or more places, in the same way or differently, with halogen, hydroxy, cyano, C-C 6 -alkyl, C 1 -C 6 -alkoxy, C-C 6 -hydroxyalkyl, C 3 -C 6 -cycloalkyl, CrC6- WO 2006/114334 49 PCT/EP2006/004226 heterocycloalkyl, C-C 6 -alkynyl, aryl, aryloxy, heteroaryl or with the group -S-C-C 6 -alkyl, -COR 6 , -NR 3 R 4 , -NR 3 C(0)-L or -NR'COOR 7 , whereby the heterocycloalkyl itself optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms and/or optionally 5 can be interrupted by one or more -C(0)- or -502 groups in the ring and/or optionally one or more double bonds can be contained in the ring, and whereby aryl, heteroaryl, C 3 -C 6 -cycloalkyl and/or the C 3 -C 6 heterocycloalkyl ring in each case itself optionally can be substituted 10 in one or more places, in the same way or differently, with cyano, halogen, hydroxy, C-C 6 -alkyl, C-C 6 -hydroxyalkyl; C-C 6 -alkoxy, C 3 -C 6 cycloalkyl, C 3 -C 6 -heterocycloalkyl, aryl, benzyl or heteroaryl that optionally is substituted in one or more places, in the same way or differently, with halogen, 15 or for the group -NR 3 R 4 , -NR 3 C(0)-L, -NR 3 (CS)NR 3 R 4 , or R 2 and R 5 together form a C 3 -C 6 -heterocycloalkyl ring, which is interrupted at least once by nitrogen and optionally can be interrupted in one or 20 more places by oxygen or sulfur and/or optionally can be interrupted by one or more -C(0)- or -502- groups in the ring and/or optionally one or more double bonds can be contained in the ring, and/or the ring itself optionally can be substituted in one or more places, in the same way or differently, with cyano, halogen, hydroxy, 25 C-C 6 -alkyl, C 3 -C 6 -cycloalkyl, C-C 6 -hydroxyalkyl, C-C 6 -alkoxyalkyl or with the group -NR 3 R 4 or -COR 6 and/or can be substituted with aryl or heteroaryl that optionally is substituted in one or more places, in the same way or differently, with halogen, C-C 6 -alkoxy or with the group -COR 6 , 30 R 3 and R 4 , independently of one another, stand for hydrogen or for C-C 6 -alkyl, CI-C 6 -alkoxy, -CO-C-C 6 -alkyl or aryl that optionally is substituted in one or more places, in the same way or differently, with halogen, hydroxy, C 3 -C 6 -heterocycloalkyl, C-C 6 -hydroxyalkoxy or with the group -NR 3 R 4 , whereby the heterocycloalkyl itself optionally can be WO 2006/114334 50 PCT/EP2006/004226 interrupted by one or more nitrogen, oxygen and/or sulfur atoms and/or optionally can be interrupted by one or more -C(O)- or -SO 2 groups in the ring and/or optionally one or more double bonds can be contained in the ring, and whereby the C 3 -C 6 -heterocycloalkyl ring 5 itself in each case optionally can be substituted in one or more places, in the same way or differently, with cyano, halogen, C-C 6 -alkyl, Cl-C 6 -hydroxyalkyl, C-C 6 -alkoxy, C 3 -C 6 -cycloalkyl or with the group -NR 3 R 4 or -CO-NR 3 R 4 , or 10 R 3 and R 4 together form a C 3 -C 6 -heterocycloalkyl ring, which is interrupted at least once by nitrogen and optionally can be interrupted in one or more places by oxygen or sulfur and/or optionally can be interrupted by one or more -C(O)- or -SO 2 - groups in the ring and/or optionally one or more double bonds can be contained in the ring 15 and/or the heterocycloalkyl ring itself optionally can be substituted in one or more places, in the same way or differently, with C-C 6 -alkyl, C 3 -C 6 -cycloalkyl, C-C 6 -hydroxyalkyl, C-C 6 -alkoxyalkyl, cyano, hydroxy or with the group -NR 3 R 4 , R 5 stands for C-C 6 -alkyl, C-C 6 -alkenyt or CI-C 6 -alkynyl that optionally is 20 substituted in one or more places, in the same way or differently, with halogen, hydroxy, cyano, C-C 6 -alkoxy, C 3 -C 6 -cycloalkyl, C 3 -C 6 heterocycloalkyl or with the group -NR 3 R 4 , whereby the heterocycloalkyl itself optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms and/or optionally can be 25 interrupted by one or more -C(O)- or -S0 2 - groups in the ring and/or optionally one or more double bonds can be contained in the ring and whereby the C 3 -C 6 -heterocycloalkyl ring itself in each case optionally can be substituted in one or more places, in the same way or differently, with cyano, halogen, C-C 6 -alkyl, C-C 6 -hydroxyalkyl, 30 C-C 6 -alkoxy, C 3 -C 6 -cycloalkyl, or with the group -NR 3 R 4 or -CO-NR 3 R 4 , R stands for hydroxy, C-C 6 -alkyl, C-C 6 -alkoxy or the group -NR 3 R 4 , RT stands for -(CH 2 )n-aryl or -(CH 2 )n-heteroaryl and n stands for an integer of 1, 2, 3, 4, 5 or 6, as well as the stereoisomers, diastereomers, enantiomers and salts thereof. WO 2006/114334 51 PCT/EP2006/004226

3. The compound of general formula I according to claim 1 or 2, in which Q stands for phenyl, A and B, independently of one another, stand for hydrogen, halogen, or for 5 C-C 4 -alkyl or pyrrolidinyl that optionally is substituted in one or more places, in the same way or differently, with halogen, hydroxy or with the group -NR 3 R 4 or -CO(NR 3 )-M, M stands for C-C 6 -alkyl that optionally is substituted in one or more places, in the same way or differently, with the group -NR 3 R 4 or C 3 -C 6 10 heterocycloalkyl, X stands for -NH-, R1 stands for C-C 4 -alkyl that optionally is substituted in one or more places, in the same way or differently, with halogen, R 2 stands for hydrogen or for C-C 6 -alkyl or C-C 6 -alkynyl that optionally is 15 substituted in one or more places, in the same way or differently, with halogen, cyano, or C-C 6 -alkoxy, R 3 and R 4 , independently of one another, stand for hydrogen or for C-C 6 -alkyl, Cl-C 6 -alkoxy, -CO-C-C 6 -alkyl or aryl that optionally is substituted in one or more places, in the same way or differently, with halogen, 20 hydroxy, C 3 -C 6 -heterocycloalkyl, C-C 6 -hydroxyalkoxy or with the group -NR 3 R 4 , whereby the heterocycloalkyl itself optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms, and/or optionally can be interrupted by one or more -C(O)- or -SO 2 groups in the ring and/or optionally one or more double bonds can be 25 contained in the ring, and whereby the C 3 -C 6 -heterocycloalkyl ring itself optionally can be substituted in one or more places, in the same way or differently, with cyano, halogen, C-C 6 -alkyl, C-C 6 hydroxyalkyl, C-C 6 -alkoxy, C 3 -C 6 -cycloalkyl, or with the group -NR 3 R 4 or -CO-NR 3 R 4 , 30 or R 3 and R 4 together form a C 3 -C 6 -heterocycloalkyl ring, which is interrupted at least once by nitrogen and optionally is interrupted in one or more places by oxygen or sulfur and/or optionally can be interrupted by one WO 2006/114334 52 PCT/EP2006/004226 or more -C(0)- or -SO 2 - groups in the ring and/or optionally one or more double bonds can be contained in the ring, and/or the heterocycloalkyl ring itself optionally can be substituted in one or more places, in the same way or differently, with C-C 6 -alkyl, 5 C 3 -C 6 -cycloalkyl, C-C 6 -hydroxyalkyl, C-C 6 -alkoxyakyl, cyano, hydroxy or with the group -NR 3 R 4 , and R stands for hydroxy or C-C 6 -alkoxy, as well as the solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts thereof. 10

4. The compound of general formula I according to any one of claims 1 to 3, in which : Q stands for phenyl, A and B, independently of one another, stand for hydrogen, halogen, hydroxy, 15 methoxy or pyrrolidinyl, X stands for -NH-, R1 stands for ethyl, R 2 stands for ethyl or propynyl, as well as the solvates, hydrates, stereoisomers, diastereomers, enantiomers and 20 salts thereof.

5. The compound of general formula I according to any one of claims 1 to 4, which is selected from the group consisting of : 25 2-Cyano-N-ethyl-2-[3-ethyl-4-oxo-5-[1-(4-pyrrolidin-1 -yl-phenyl)-meth-(Z)-ylidene] thiazolidin-(2Z)-ylidene]-acetamide ; 2-Cyano-N-ethyl-2-[3-ethyl-5-[1-(3-hydroxy phenyl)-meth-(Z)-ylidene]-4-oxo-thiazolidin-(2Z)-ylidene]-acetamide ; 2-Cyano-N ethyl-2-[3-ethyl-5-[1-(4-hydroxy-phenyl)-meth-(Z)-ylidene]-4-oxo-thiazolidin-(2Z) ylidene]-acetamide ; 2-[5-[1-(4-Bromo-phenyl)-meth-(Z)-ylidene]-3-ethyl-4-oxo 30 thiazolidin-(2Z)-ylidene]-2-cyano-N-ethyl-acetamide ;2-Cyano-N-ethyl-2-[3-ethyl-5 [1 -(4-hydroxy-3-methoxy-phenyl)-meth-(Z)-ylidene]-4-oxo-thiazolidin-(2Z)-ylidene] acetamide ;2-Cyano-N-ethyl-2-[3-ethyl-5-[1-(3-methoxy-phenyl)-meth-(Z)-ylidene] 4-oxo-thiazolidin-(2Z)-ylidene]-acetamide ;2-Cyano-2-[3-ethy-5-[1-(3-hydroxy phenyl)-meth-(Z)-ylidene] -4-oxo-thiazolidin-(2Z)-ylidene] -N-prop-2-ynyl-acetamide WO 2006/114334 53 PCT/EP2006/004226 2-Cyano-2-[3-ethyl-5-[1 -(4-hydroxy-phenyl)-meth-(Z)-ylidene]-4-oxo-thiazolidin (2Z)-ytidene]-N-prop-2-ynyl-acetamide ;2-Cyano-2-[3-ethyt-5-[1-(4-hydroxy-3 methoxy-phenyl)-meth-(Z)-ylidene]-4-oxo-thiazolidin-(2Z)-ylidene]-N-prop-2-ynyt acetamide ; 2-Cyano-2-[3-ethyl-4-oxo-5-[1-(4-pyrrotidin-1-y-phenyt)-meth-(Z) 5 ylidene]-thiazotidin-(2Z)-ytidene]-N-prop-2-ynyt-acetamide ;2-Cyano-2-[3-ethyl-5 [1 -(3-nitro-phenyl)-meth-(Z)-ylidene]-4-oxo-thiazoidin-(2Z)-ylidene]-N-prop-2-ynyl acetamide ; 2-Cyano-2-[3-ethyl-5-[1-(3-hydroxy-phenyt)-meth-(Z)-ylidene]-4-oxo thiazolidin-(2Z)-ytidene]-N-(2-hydroxy-1,1-dimethyl-ethyl)-acetamide ; 2-Cyano-2 [3-ethyt-5-[1-(3-methoxy-phenyl)-meth-(Z)-ylidene]-4-oxo-thiaz-olidin-(2Z) 10 ytidene]-N-(2-hydroxy-1,1-dimethyl-ethyl)-acetamide ; and 2-Cyano-2-[3-ethyl-5-[1 (3-nitro-phenyl)-meth-(Z)-ylidene]-4-oxo-thiazolidin-(2Z)-ylidene]-N-(2-hydroxy- 1, 1 dimethyl-ethyl) -acetamide.

6. A method of preparing a compound of general formula (1) according to 15 claim 1, wherein a carboxylic acid of general formula (3) A 0 B OH B INON O R (3) 20 is allowed to react with a compound of general formula (3') R 2 -XH (3') 25 thus providing a compound of general formula (1) 54 WO 2006/114334 PCT/EP2006/004226 A 0 B N R2 (I ), 5 in which formulae (3), (3') and (1), the definitions of substituents R', R 2 , A, B, Q, and X being according to claim 1.

7. The method according to claim 6, wherein said carboxylic acid of general formula (3) is prepared by allowing an allyl ester of general formula (2) 10 A 0 N 0 R (2) 15 to be saponified in the presence of Pd-tetrakis-triphenylphosphine and barbituric acid, in which formula (2) the definitions of substituents R', A, B, and Q being according to claim 1.

8. The method according to claim 7, wherein said allyl ester of general 20 formula (2) is prepared by allowing a thiazolidinone of general formula (1): 0/ N CN 0 R1 WO 2006/114334 PCT/EP2006/004226 (1) to be condensed with an aldehyde of general formula (1'): H A 0 Q 5 B (1') in which formulae (1) and (1'), the definitions of substituents R 1 , A, B, and Q being 10 according to claim 1.

9. A method of preparing a compound of general formula (1) according to claim 1, wherein a thiazolidinone of general formula (5) 15 0/2 JNN O R (5) 20 is allowed to be condensed with an aldehyde of general formula (1'): H A 0 Q B (1') WO 2006/114334 56 PCT/EP2006/004226 thus providing a compound of general formula (1) A 0 Q X- R2 B N CN 0 \ R 5 (I ), in which formulae (5), (1') and (I), the definitions of substituents R', R 2 , A, B, Q, and X being according to claim 1. 10

10. The method according to claim 9, wherein said thiazolidinone of general formula (5) is prepared by allowing a carboxylic acid of general formula (4) 0 S OH N > CN 0 R' 15 (4) to react with a compound of general formula (3'): 20 R 2 -XH (3') ; in which formulae (4) and (3'), the definitions of substituents R', R 2 and X being 25 according to claim 1. 57 WO 2006/114334 PCT/EP2006/004226

11. The method according to claim 10, wherein said carboxylic acid of general formula (4) is prepared by allowing a thiazolidinone of general formula (1): S 0 N CN 5 0 \ R (1) to be saponified in the presence of Pd-tetrakis-triphenylphosphine and barbituric 10 acid, in which formula (1) the definition of the substituent R' being according to claim 1.

12. Use of a compound of general formula I according to any one of claims 1 to 5, or of a compound as obtained according to any one of claims 6 to 11, for the 15 production of a pharmaceutical agent for treating cancer, auto-immune diseases, chemotherapy agent-induced alopecia and mucositis, cardiovascular diseases, infectious diseases, nephrological diseases, chronic and acute neurodegenerative diseases and viral infections. 20

13. Use according to claim 12, wherein cancer is defined as solid tumours and leukemia; auto-immune diseases are defined as psoriasis, alopecia and multiple sclerosis; cardiovascular diseases are defined as stenoses, arterioscleroses, and restenoses; infectious diseases are defined as diseases that are caused by unicellular parasites; nephrological diseases are defined as glomerulonephritis; 25 chronic neurodegenerative diseases are defined as Huntington's disease, amyotrophic lateral sclerosis, Parkinson's disease, AIDS dementia and Alzheimer's disease; acute neurodegenerative diseases are defined as ischemias of the brain and neurotraumas; and viral infections are defined as cytomegalic infections, herpes, hepatitis B and C, and HIV diseases. 30 WO 2006/114334 58 PCT/EP2006/004226

14. A pharmaceutical agent, characterized in that it contains at least one compound according to claims 1 to 5, or as obtained by a method according to any one of claims 6 to 11. 5

15. The pharmaceutical agent according to claim 14 for treating cancer, autoimmune diseases, cardiovascular diseases, infectious diseases, nephrological diseases, neurodegenerative diseases and viral infections.

16. A compound according to any one of claims 1 to 5, or as obtained 10 according to any one of claims 6 to 11, or a pharmaceutical agent according to claim 14 or 15, together with a suitable formulation substance and/or vehicle.

17. Use of a compound of general formula I according to any one of claims 1 to 5, or as obtained by a method according to any one of claims 6 to 11, or of a 15 pharmaceutical agent according to claim 14 or 15, as an inhibitor of a polo-like kinase.

18. Use according to claim 17, wherein said kinase is Plk1, Plk2, Plk3 or Plk4. 20

19. Use of a compound of general formula I according to any one of claims 1 to 5, or as obtained according to any one of claims 6 to 11, in the form of a pharmaceutical preparation for enteral, parenteral and oral administration.