Literaturverzeichnis

(1) Coleman, K.G.; Lyssikatos, J.P.; Ynag, B.V.: Chemical inhibitors of cyclin-dependent kinases. Annu. Rep. Med. Chem. 1997, 32, 171-179.
(2) Kelland, L.R.: Flavopiridol, the first cyclin-dependent kinase inhibitor to enter the clinic: current status. Expert Opin. Invest. Drugs 2000, 9, 2903-2911.
(3) Sedlacek, H.H.; Czech, J.; Naik, R.; Kaur, G.; Worland, P.; Losiewicz, M.; Parker, B.; Carlson, B.; Smith, A.; Senderowicz, A.; Sausville, E.: Flavopiridol (L86-8275, NSC-649890), a new kinase inhibitor for tumor therapy. Int. J. Oncol. 1996, 9, 1143-1168.
(4) Walker, D.H.: Small-molecule inhibitors of cyclin-dependent kinases: molecular tools and potential therapeutics. Curr. Top. Microbiol. Immunol. 1998, 227, 149-165.
(5) Kunick, C.: Synthese von 7,12-Dihydro-indolo[3,2-d][1]benzazepin-6(5H)-onen und 6,11-Dihydro-thieno[3',2':2,3]azepino[4,5-b]indol-5(4H)-on. Arch. Pharm. (Weinheim, Ger.) 1992, 325, 297-299.
(6) Kunick, C.: Fused azepinones with antitumor activity. Curr. Pharm. Des. 1999, 5, 181-194.
(7) Leost, M.; Schultz, C.; Link, A.; Wu, Y.-Z.; Biernat, J.; Mandelkow, E.-M.; Bibb, J.A.; Snyder, G.L.; Greengard, P.; Zaharevitz, D.W.; Gussio, R.; Senderowicz, A.; Sausville, E.; Kunick, C.; Meijer, L.: Paullones are potent inhibitors of glycogen synthase kinase-3b and cyclin-dependent kinase 5/p25. Eur. J. Biochem. 2000, 267, 1-13.
(8) Schultz, C.: Antitumoraktive [d]-anellierte [1]Benzazepin-2-one. Dissertation Universität Hamburg 1999.
(9) Schultz, C.; Link, A.; Leost, M.; Zaharevitz, D.W.; Gussio, R.; Sausville, E.A.; Meijer, L.; Kunick, C.: Paullones, a series of cyclin-dependent kinase inhibitors: synthesis, evaluation of CDK1/ cyclin B inhibition, and in vitro antitumor activity. J. Med. Chem. 1999, 42, 2909-2919.
(10) Voet, D.; Voet, J.: Biochemie, VCH Verlagsgesellschaft mbH, Weinheim (Bundesrepublik Deutschland), 1992.
(11) Leclerc, S.; Garnier, M.; Hoessel, R.; Marko, D.; Bibb, J.A.; Snyder, G.L.; Greengard, P.; Biernat, J.; Wu, Y.-Z.; Mandelkow, E.-M.; Eisenbrand, G.; Meijer, L.: Indirubins inhibit Glycogen Synthase Kinase-3b and CDK5/p25, two protein kinases involved in abnormal tau phosphorylation in Alzheimer's disease. J. Biol. Chem. 2001, 276, 251-260.
(12) Sielecki, T.M.; Boylan, J.F.; Benfield, P.A.; Trainor, G.L.: Cyclin-dependent kinase inhibitors: Useful targets in cell cycle regulation. J. Med. Chem. 2000, 43, 1-18.
(13) Krauss, G.: Regulation des Zellzyklus, Wiley-VCH, Weinheim (Bundesrepublik Deutschland), 1997, 392-463.
(14) Jeffrey, P.D.; Russo, A.A.; Polyak, K.; Gibbs, E.; Hurwitz, J.; Massague, J.; Pavletich, N.P.: Mechanism of CDK activation revealed by the structure of a cyclin A-CDK2 complex. Nature 1995, 376, 313-320.
(15) Morgan, D.O.: Cyclin-dependent kinases: engines, clocks, and microprocessors. Annu. Rev. Cell Dev. Biol. 1997, 13, 261-291.
(16) Barvian, M.; Boschelli, D.H.; Crossrow, J.; Dobrusin, E.; Fattaey, A.; Fritsch, A.; Fry, D.; Harvey, P.; Keller, P.; Garrett, M.; La, F.; Leopold, W.; McNamara, D.; Quin, M.; Trumpp-Kallmeyer, S.; Toogood, P.; Wu, Z.; Zhang, E.: Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases. J. Med. Chem. 2000, 43, 4606-4616.
(17) Gray, N.; Detivaud, L.; Doerig, C.; Meijer, L.: ATP-site directed inhibitors of cyclin-dependent kinases. Curr. Med. Chem. 1999, 6, 859-875.
(18) Rosania, G.R.; Chang, Y.-T.: Targeting hyperproliferative disorders with cyclin dependent kinase inhibitors. Expert Opin. Ther. Patents 2000, 10, 1-13.
(19) Meijer, L.; Thunnissen, A.-M.W.H.; White, A.W.; Garnier, M.; Nikolic, M.; Tsai, L.-H.; Walter, J.; Cleverly, K.E.; Salinas, P.C.; Wu, Y.-Z.; Biernat, J.; Mandelkow, E.-M.; Kim, S.-H.; Pettit, G.R.: Inhibition of cyclin-dependent kinases, GSK-3b and CK1 by hymenialdisine, a marine sponge constituent. Chem. Biol. 2000, 7, 51-63.
(20) Meijer, L.; Leclerc, S.; Leost, M.: Properties and potential applications of chemical inhibitors of cyclin-dependent kinases. Pharmacol. Ther. 1999, 82, 279-284.
(21) Mandelkow, E.: The tangled tale of tau. Nature 1999, 402, 588-589.
(22) Morgan, D.O.: Principles of CDK regulation. Nature 1995, 374, 131-134.
(23) Manser, E.; Chong, C.; Zhao, Z.S.; Leung, T.; Michael, G.; Hall, C.; Lim, L.: Molecular cloning of a new member of the p21-Cdc42/Rac-activated kinase (PAK) family. J. Biol. Chem. 1995, 270, 25070-25078.
(24) Yee, A.; Nichols, M.A.; Wu, L.; Hall, F.L.; Kobayashi, R.; Xiong, Y.: Molecular cloning of CDK7-associated human MAT1, a cyclin-dependent kinase-activating kinase (CAK) assembly factor. Cancer Res. 1995, 55, 60-6062.
(25) Fujinaga, K.; Taube, R.; Wimmer, J.; Cujec, T.P.; Peterlin, B.M.: Interactions between human cyclin T, Tat, and the transactivation response element (TAR) are disrupted by a cysteine to tyrosine substitution found in mouse cyclin T. Proc. Natl. Acad. Sci. U.S.A. 1999, 4, 1285-1290.
(26) Webster, K.R.: The therapeutic potential of targeting the cell cycle. Expert Opin. Invest. Drugs 1998, 7, 865-887.
(27) Draetta, G.; Pagano, M.: Cell cycle control and cancer. Annu. Rep. Med. Chem. 1996, 31, 241-248.
(28) Kim, S.-H.: Structure-based inhibitor design for CDK2, a cell cycle controlling protein kinase. Pure Appl. Chem. 1998, 70, 555-565.
(29) Garrett, M.D.; Fattaey, A.: CDK inhibition and cancer therapy. Curr. Opin. Genet. Dev. 1999, 9, 104-111.
(30) Pavletich, N.P.: Mechanisms of cyclin-dependent kinase regulation: structures of cdks, their cyclin activators, and cip and INK4 inhibitors. J. Mol. Biol. 1999, 287, 821-828.
(31) Berman, H.M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T.N.; Weissig, H.; Shindyalov, I.N.; Bourne, P.E.: The Protein Data Bank. Nucleic Acids Res. 2000, 28, 235-242.
(32) Schulze-Gahmen, U.; De Bondt, H.L.; Kim, S.-H.: High-resolution crystal structures of human cyclin-dependent kinase 2 with and without ATP: bound waters and natural ligand as guides for inhibitor design. J. Med. Chem. 1996, 39, 4540-4546.
(33) SYBYL 6.7, Tripos Inc., 1699 South Hanley Rd., St. Louis, Missouri, 63144, USA.
(34) Kraker, A.J.; Booher, R.N.: New targets in cell cycle regulation. Annu. Rep. Med. Chem. 1999, 34, 247-256.
(35) Arris, C.E.; Boyle, F.T.; Calvert, A.H.; Curtin, N.J.; Endicott, J.A.; Garman, E.F.; Gibson, A.E.; Golding, B.T.; Grant, S.; Griffin, R.J.; Jewsbury, P.; Johnson, L.N.; Lawrie, A.M.; Newell, D.R.; Noble, M.E.M.; Sausville, E.A.; Schultz, R.; Yu, W.: Identification of novel purine and pyrimidine cyclin-dependent kinase inhibitors with distinct molecular interactions and tumor cell growth inhibition profiles. J. Med. Chem. 2000, 43, 2797-2804.
(36) Russo, A.A.; Jeffrey, P.D.; Pavletich, N.P.: Structural basis of cyclin-dependent kinase activation by phosphorylation. Nat. Struct. Biol. 1996, 3, 696-700.
(37) Kamb, A.: Cyclin-dependent kinase inhibitors and human cancer. Curr. Top. Microbiol. Immunol. 1998, 227, 139-148.
(38) Brooks, G.; La Thangue, N.B.: The cell cycle and drug discovery: the promise and the hope. Drug Discovery Today 1999, 4, 455-464.
(39) Russo, A.A.; Jeffrey, P.D.; Patten, A.K.; Massague, J.; Pavletich, N.P.: Crystal structure of the p27 KIP1 cyclin-dependent kinase inhibitor bound to the cyclin A-CDK2-complex. Nature 1996, 382, 325-331.
(40) Munk, K.: Grundstudium Biologie, Spektrum, Akademischer Verlag GmbH, Heidelberg, Berlin, 2000.
(41) Broers, J.L.V.; Machiels, B.M.; van Eys, G.J.J.M.; Kuijpers, H.J.H.; Manders, E.M.M.; van Driel, R.; Ramaekers, C.S.: Dynamics of the nuclear lamina as monitored by GFP-tagged A-type lamins. J. Cell Science 1999, 112, 3463-3475.
(42) Yamamoto, H.; Monden, T.; Miyoshi, H.; Izawa, H.; Ikeda, K.; Tsujie, M.; Ohnishi, T.; Sekimoto, M.; Tomita, N.; Monden, M.: Cdk2/cdc2 expression in colon carcinogenesis and effects of cdk2/cdc2 inhibitor in colon cancer cells. Int. J. Oncol. 1998, 13, 233-239.
(43) Meijer, L.: Chemical inhibitors of cyclin-dependent kinases. Trends Cell Biol. 1996, 6, 393-397.
(44) Albrecht, T.; Thompson, E.A.; Bresnahan, W.; Meijer, L.: Suppression of cyclin kinase 2 activity for prevention and treatment of DNA viral infections. PCT Int. Appl. WO 98 39007, 1998.
(45) Pippin, J.W.; Qu, Q.; Meijer, L.; Shankland, S.J.: Direct in vivo inhibition of the nuclear cell cycle cascade in experimental mesangial proliferative glomerulonephritis with roscovitine, a novel cyclin-dependent kinase antagonist. J. Clin. Invest. 1997, 100, 2512-2520.
(46) Pei, J.-J.; Grundke-Iqbal, I.; Iqbal, K.; Bogdanovic, N.; Winblad, B.; Cowburn, R.F.: Accumulation of cyclin-dependent kinase 5 (cdk5) in neurons with early stages of Alzheimer's disease neurofibrillary degeneration. Brain Res. 1998, 797, 267-277.
(47) Osuga, H.; Osuga, S.; Wang, F.; Fetni, R.; Hogan, M.J.; Slack, R.S.; Hakim, A.M.; Ikeda, J.-E.; Park, D.S.: Cyclin-dependent kinases as a therapeutic target for stroke. Proc. Natl. Acad. Sci. USA 2000, 97, 10254-10259.
(48) Davis, S.T.; Benson, B.G.; Bramson, H.N.; Chapman, D.E.; Dickerson, S.H.; Dold, K.M.; Eberwein, D.J.; Edelstein, M.; Frye, S.V.; Gampe Jr., R.T.; Griffin, R.J.; Harris, P.A.; Hassell, A.M.; Holmes, W.D.; Hunter, R.N.; Knick, V.B.; Lackey, K.; Lovejoy, B.; Luzzio, M.J.; Murray, D.; Parker, P.; Rocque, W.J.; Shewchuk, L.; Veal, J.M.; Walker, D.H.; Kuyper, L.F.: Prevention of chemotherapy-induced alopecia in rats by CDK-inhibitors. Science 2001, 291, 134-137.
(49) Colas, P.; Cohen, B.; Jessen, T.; Grishina, I.; McCoy, J.; Brent, R.: Genetic selection of peptide aptamers that recognize and inhibit cyclin-dependent kinase 2. Nature 1996, 380, 548-550.
(50) Thompson, A.M.; Bridges, A.J.; Fry, D.W.; Kraker, A.J.; Denny, W.A.: Tyrosine kinase inhibitors. 7. 7-Amino-4-(phenylamino)- and 7-amino-4-[(phenylmethyl)amino]-pyrido[4,3-d]pyrimidines: a new class of inhibitors of tyrosine kinase activity of the epidermal growth factor receptor. J. Med. Chem. 1995, 38, 3780-3788.
(51) Chang, Y.-T.; Gray, N.S.; Rosania, G.R.; Sutherlin, D.P.; Kwon, S.; Norman, T.C.; Sarohia, R.; Leost, M.; Meijer, L.; Schultz, P.G.: Synthesis and application of functionally diverse 2,6,9-trisubstituted purine libraries as CDK inhibitors. Chem. Biol. 1999, 6, 361-375.
(52) Meijer, L.; Kim, S.-H.: Chemical inhibitors of cyclin-dependent kinases. Methods Enzymol. 1997, 283, 113-128.
(53) Vesely, J.; Havlicek, L.; Strnad, M.; Blow, J.J.; Donella-Deana, A.; Pinna, L.; Letham, D.S.; Kato, J.-Y.; Detivaud, L.; Leclerc, S.; Meijer, L.: Inhibition of cyclin-dependent kinases by purine analogues. Eur. J. Biochem. 1994, 224, 771-786.
(54) Ducrot, P.; Legraverend, M.; Grierson, D.S.: 3D-QSAR CoMFA on cyclin-dependent kinase inhibitors. J. Med. Chem. 2000, 43, 4098-4108.
(55) Gussio, R.; Zaharevitz, D.W.; McGrath, C.F.; Pattabiraman, N.; Kellogg, G.E.; Schultz, C.; Link, A.; Kunick, C.; Leost, M.; Meijer, L.; Sausville, E.A.: Structure-based design modifications of the paullone moleculare scaffold for cyclin-dependent kinase inhibition. Anti-Cancer Drug Des. 2000, 15, 53-66.
(56) Legraverend, M.; Tunnah, P.; Noble, M.; Ducrot, P.; Ludwig, O.; Grierson, D.S.; Leost, M.; Meijer, L.; Endicott, J.: Cyclin-dependent kinase inhibition by new C-2 alkynylated purine derivatives and molecular structure of a CDK2-inhibitor complex. J. Med. Chem. 2000, 43, 1282-1292.
(57) Shewchuk, L.; Hassell, A.; Wisely, B.; Rocque, W.; Holmes, W.; Veal, J.; Kuyper, L.F.: Binding mode of the 4-anilinoquinazoline class of protein kinase inhibitor: X-ray crystallographic studies of 4-anilinoquinazolines bound to cyclin-dependent kinase 2 and p38 kinase. J. Med. Chem. 2000, 43, 133-138.
(58) Whiteway, M.; Dignard, D.; Thomas, D.Y.: Dominant negative selection of heterologous genes: isolation of Candida albicans genes that interfere with Saccharomyces cerevisiae mating factor-induced cell cycle arrest. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 9410-9414.
(59) Abraham, R.T.; Acquarone, M.; Andersen, A.; Asensi, A.; Belle, R.; Berger, F.; Bergounioux, C.; Brunn, G.; Buquet-Fagot, C.; Fagot, D.; Glab, N.; Goudeau, H.; Goudeau, M.; Guerrier, P.; Houghton, P.; Hendriks, H.; Kloareg, B.; Lippai, M.; Marie, D.; Maro, B.; Meijer, L.; Mester, J.; Mulner-Lorillon, O.; Poulet, S.A.; Schierenberg, E.; Schutte, B.; Vaulot, D.; Verlhac, M.H.: Cellular effects of olomoucine, an inhibitor of cyclin-dependent kinases. Biol. Cell 1995, 83, 105-120.
(60) De Azevedo, W.F.; Leclerc, S.; Meijer, L.; Havlicek, L.; Strnad, M.; Kim, S.-H.: Inhibition of cyclin-dependent kinases by purine analogues. Crystal structure of human cdk2 complexed with roscovitine. Eur. J. Biochem. 1997, 243, 518-526.
(61) Gray, N.S.; Wodicka, L.; Thunnissen, A.-M.W.H.; Norman, T.C.; Kwon, S.; Espinoza, F.H.; Morgan, D.O.; Barnes, G.; Leclerc, S.; Meijer, L.; Kim, S.-H.; Lockhart, D.J.; Schultz, P.G.: Exploiting chemical libraries, structure, and genomics in the search of kinase inhibitors. Science 1998, 281, 533-538.
(62) Oh, C.-H.; Lee, S.-C.; Lee, K.-S.; Woo, E.-R.; Hong, C.Y.; Yang, B.-S.; Baek, D.J.; Cho, J.-H.: Synthesis and biological activities of C-2, N-9 substituted 6-benzylaminopurine derivatives as cyclin-dependent kinase inhibitor. Arch. Pharm. Pharm. Med. Chem. 1999, 332, 187-190.
(63) Legraverend, M.; Ludwig, O.; Bisagni, E.; Leclerc, S.; Meijer, L.; Giocanti, N.; Sadri, R.; Favaudon, V.: Synthesis and in vitro evaluation of novel 2,6,9-trisubstituted purines acting as cyclin-dependent kinase inhibitors. Bioorg. Med. Chem. 1999, 7, 1281-1293.
(64) Legraverend, M.; Ludwig, O.; Bisagni, E.; Leclerc, S.; Meijer, L.: Synthesis of C2 alkynylated purines, a new family of potent inhibitors of cyclin-dependen kinases. Bioorg. Med. Chem. Lett. 1998, 8, 793-798.
(65) Imbach, P.; Capraro, H.-G.; Furet, P.; Mett, H.; Meyer, T.; Zimmermann, J.: 2,6,9-Trisubstituted purines: optimization towards highly potent and selective CDK1 inhibitors. Bioorg. Med. Chem. Lett. 1999, 9, 91-96.
(66) Griffin, R.J.; Calvert, A.H.; Curtin, N.J.; Newell, D.R.; Golding, B.T.; Endicott, J.A.; Noble, M.E.M.; Boyle, F.T.; Jewsbury, P.J.: Preparation of cyclohexylmethoxypyrimidineamines and analogs as cyclin dependent kinase inhibitors. PCT Int. Appl. WO 99 50,251 1999.
(67) Löffler, G.; Petrides, P.E.: Biochemie und Pathobiochemie, 5. Auflage, Springer-Verlag, Berlin, Heidelberg, New York, 1997.
(68) Carlson, B.A.; Dubay, M.M.; Sausville, E.A.; Brizuela, L.; Worland, P.: Flavopiridol induces G1 arrest with inhibition of cyclin-dependent kinase (CDK) 2 and CDK4 in human breast carcinoma cells. Cancer Res. 1996, 56, 2973-2978.
(69) Kelley, M.J.; Nakagawa, K.; Dent, B.R. Cyclin dependent kinase (CDK)4 inhibitors and their use for treating cancer. In PCT Int. Appl. WO 98 49,146, 1998.
(70) Hu, M.C.; Wang, Y.P.; Mikhail, A.; Qui, W.R.; Tan, T.H.: Murine p38-delta mitogen-activated protein kinase, a developmentally regulated protein kinase that is activated by stress and proinflammatory cytokines. J. Biol. Chem. 1999, 274, 7095-7102.
(71) Kumar, S.; McDonnel, P.C.; Gum, R.J.; Hand, A.T.; Lee, J.C.; Young, P.R.: Novel homologues of CSBP / p38 MAP kinase: activation, substrate specificity and sensitivity to inhibition by pyridinyl imidazoles. Biochem. Biophys. Res. Commun. 1997, 235, 533-538.
(72) Thompson, A.M.; Murray, D.K.; Ellicott, W.L.; Fry, D.W.; Nelson, J.A.; Showalter, H.D.H.; Roberts, B.J.; Vincent, P.W.; Denny, W.A.: Tyrosine kinase inhibitors. 13. Structure-activity relationships for soluble 7-substituted 4-[(3-bromophenyl)amino]pyrido[4,3-d]pyrimidines designed as inhibitors of the tyrosine kinase activity of the epidermal growth factor receptor. J. Med. Chem. 1997, 40, 3915-3925.
(73) Rewcastle, G.W.; Murray, D.K.; Ellicott, W.L.; Fry, D.W.; Howard, C.T.; Nelson, J.A.; Roberts, B.J.; Vincent, P.W.; Showalter, H.D.H.; Winters, R.T.; Denny, W.A.: Tyrosine kinase inhibitors. 14. Structure-activity relationships for methylamino-substituted derivatives of 4-[(3-bromophenyl)amino]-6-(methylamino)-pyrido[3,4-d]pyrimidine (PD 158780), a potent and specific inhibitor of the tyrosine kinase activity of receptors for the EGF family of growth factors. J. Med. Chem. 1998, 41, 742-751.
(74) Dobrusin, E.M.; Hamby, J.M.; Kramer, J.B.; Schroeder, M.C.; Showalter, H.D.H.; Toogood, P.; Trumpp-Kallmeyer, S.A.: Preparation of oxopyrido- and -pyrimidopyrimidines as cellular proliferation inhibitors. PCT Int. Appl. WO 99 61,444 2000.
(75) El-Subbagh, H.I.; Abadi, A.H.; Al-Khawad, I.E.; Al-Rashood, K.A.: Synthesis and antitumor activity of some new substituted quinolin-4-one and 1,7-naphthyridin-4-one analogs. Arch. Pharm. Pharm. Med. Chem. 1999, 332, 19-24.
(76) Chong, W.K.; Chu, S.S.; Duvadie, R.R.; Li, L.; Xiao, W.: 4-Aminothiazole derivatives, their preparation and their use as inhibitors of cyclin-dependent kinases. PCT Int. Appl. WO 99 21845 1999.
(77) Kent, L.L.; Hull-Campbell, N.E.; Lau, T.; Wu, J.C.; Thompson, S.A.; Nori, M.: Characterization of novel inhibitors of cyclin-dependent kinases. Biochem. Biophys. Res. Commun. 1999, 260, 768-774.
(78) Sun, L.; Tran, N.; Tang, F.; App, H.; Hirth, P.; McMahon, G.; Tang, C.: Synthesis and biological evaluations of 3-substituted indolin-2-ones: A novel class of tyrosine kinase inhibitors that exhibit selectivity toward particular receptor tyrosin kinases. J. Med. Chem. 1998, 41, 2588-2603.
(79) Grell, W.; Walter, R.; Heckel, A.; Himmelsbach, F.; Wittneben, H.; van Meel, J.; Redemann, N.; Haigh, R.: Preparation of 3-(a-heteroarylaminobenzylidene)-2-indolinones as Cyclin dependent kinase inhibitors. Ger. Offen. DE 19,815020 1999.
(80) Misra, R.N.; Kimball, S.D.; Rawlines, D.B.; Webster, K.R.; Bursuker, I.: Preparation of benzoylpyrazolo[3,4-b]pyridines and analogs as cyclin dependent kinase inhibitors. PCT Int. Appl. WO 99 30,710 1999.
(81) Markwalder, J.A.; Seitz, S.P.; Sherk, S.R.: Preparation of 6-substituted pyrazolo[3,4-d]pyrimidin-4-ones as cyclin dependent kinase inhibitors. PCT Int. Appl. WO 00 21,926 2000.
(82) Hoessel, R.; Leclerc, S.; Endicott, J.; Nobel, M.E.M.; Lawrie, A.; Tunnah, P.; Leost, M.; Damiens, E.; Marie, D.; Marko, D.; Niederberger, E.; Tang, W.; Eisenbrand, G.; Meijer, L.: Indirubin, the active constituent of a Chinese antileukaemia medicine, inhibits cyclin-dependent kinases. Nat. Cell Biol. 1999, 1, 60-67.
(83) Eisenbrand, G.: Use of indigoid bisindole derivatives for the manufacture of a medicament to inhibit cyclin dependent kinases. PCT Int. Appl. WO 99 62,503 2000.
(84) Zaharevitz, D.W.; Gussio, R.; Leost, M.; Senderowicz, A.; Lahusen, T.; Kunick, C.; Meijer, L.; Sausville, E.A.: Discovery and initial characterization of the paullones, a novel class of small-molecule inhibitors of cyclin-dependent kinases. Cancer Res. 1999, 59, 2566-2569.
(85) Kunick, C.: Synthese [b]-kondensierter Azepindione durch Dealkoxycarbonylierung. Arch. Pharm. (Weinheim, Ger.) 1991, 324, 579-581.
(86) Bleeker, C.: [c]-Anellierte 1-Benzazepine - Synthese und antivirale Eigenschaften. Dissertation Universität Hamburg 1998.
(87) Chen, J.-l.; Steglich, W.: Synthesis of some benzofuronaphthyridines and benzofuronaphthyridine derivatives. J. Heterocycl. Chem. 1993, 30, 909-912.
(88) MacPhillamy, H.B.; Dziemian, R.L.; Lucas, R.A.; Kuehne, M.E.: The alkaloids of Tabernanthe iboga. Part VI. The synthesis of the selenium dehydrogenation products from ibogamine. J. Am. Chem. Soc. 1958, 80, 2172-2178.
(89) Sucharda, E.: Über eine neue Darstellungsmethode der Chinolinsäure und einiger Derivate derselben. Chem. Ber. 1925, 58, 1727-1729.
(90) Oakes, V.; Pascoe, R.; Rydon, H.N.: Polyazanaphthalenes. Part III. Some derivatives of 1:3:5- and 1:3:8-triazanaphthalene. J. Chem. Soc. 1956, 1045-1054.
(91) Chen, Q.; Deady, L.W.: Synthesis of some benzo[b][1,8] and [1,5]naphthyridines. J. Heterocycl. Chem. 1992, 29, 1197-1201.
(92) Link, A.: Antitumoraktive Pyrido[3,2-d]-1-benzazepine. Dissertation Universität Hamburg 1996.
(93) Kunick, C.: unveröffentlichte Ergebnisse.
(94) Da Settimo, A.; Saettone, M.F.: The nitration of some phenyl substituted indoles. Tetrahedron 1965, 21, 823-829.
(95) Hellmann, H.; Opitz, G.: a-Aminoalkylierungen, Verlag Chemie, GmbH, Weinheim / Bergstraße, 1969.
(96) Tramontini, M.: Advances in the chemistry of Mannich bases. Synthesis 1973, 703-775.
(97) Mannich, C.; Reichert, B.: Über eine Synthese von Chinolinderivaten mit basicher Seitenkette. Arch. Pharm. Ber. Dtsch. Pharm. Ges. 1933, 271, 116-127.
(98) Nisbet, H.B.: Pyrazoline ring formation. Part I. The action of phenylhydrazine on some saturated and unsaturated b-amino-ketones. J. Chem. Soc. (London) 1945, 126-129.
(99) Nisbet, H.B.: Pyrazoline local anaesthetics. Part I. Derivatives of benzylidene- and anisylidene-acetone. J. Chem. Soc. 1938, 1237-1241.
(100) Mannich, C.; Schütz, M.: Über die Synthese von ungesättigten 1,3-Ketobasen und ihre Reduktionsprodukte. Arch. Pharm. Ber. Dtsch. Pharm. Ges. 1927, 265, 684-695.
(101) Becker, H.G.O.; Berger, W.; Domschke, G.; Fanghänel, E.; Faust, J.; Fischer, M.; Gentz, F.; Gewald, K.; Gluch, R.; Mayer, R.; Müller, K.; Pavel, D.; Schmidt, H.; Schollberg, K.; Schwetlick, K.; Seiler, E.; Zeppenfeld, G.: Organikum, Barth, Deutscher Verlag der Wissenschaften, Leipzig, 1993, 485.
(102) Hösch, C.: b-Substituierte g-Oxosulfone - Darstellung, kinetische und enzymatische Untersuchungen. Dissertation Universität Hamburg 1997.
(103) Lindsay, B.S.; Christiansen, H.C.; Copp, B.R.: Structural studies of cytotoxic marine alkaloids: Synthesis of novel ring-E analogues of Ascididemin and their in vitro and in vivo biological evaluation. Tetrahedron 2000, 56, 497-505.
(104) Hulin, B.; Clark, D.A.; Goldstein, S.W.; McDermott, R.E.; Dambeck, P.J.; Kappeler, W.H.; Lamphere, C.H.; Lewis, D.M.; Rizzi, J.P.: Novel thiazolidine-2,4-diones as potent euglycemic agents. J. Med. Chem. 1992, 35, 1853-1864.
(105) Salaski, E.J.: Synthesis of imidazobenzazepinthiones: A new series of HIV-1 reverse transcriptase inhibitors. Tetrahedron Lett. 1995, 36, 1387-1390.
(106) Hesse, M.; Meier, H.; Zeeh, B.: Spektroskopische Methoden in der organischen Chemie, 5. überarbeitete Auflage, G. Thieme, Stuttgart, 1995, 152-153.
(107) Boyd, M.R.; Paull, K.D.: Some practical considerations and applications of the National Cancer Institute in vitro anticancer drug discovery screen. Drug Dev. Res. 1995, 34, 91-109.
(108) Monks, A.; Scudiero, D.A.; Johnson, G.S.; Paull, K.D.; Sausville, E.A.: The NCI anti-cancer drug screen: a smart screen to identify effectors of novel targets. Anti-Cancer Drug Des. 1997, 12, 533-541.
(109) Paull, K.D.; Shoemaker, R.H.; Hodes, L.; Monks, A.; Scudiero, D.A.; Rubinstein, L.; Plowman, J.; Boyd, M.R.: Display and analysis of patterns of differential activity of drugs against human tumor cell lines: development of meangraph and COMPARE algorithm. J. Natl. Cancer Inst. 1989, 81, 1088-1092.
(110) Robert, J.: Anticancer drug screening with in vitro models. Drugs Fut. 1997, 22, 739-746.
(111) Kunick, C.; Leost, M.; Meijer, L. unveröffentlichte Resultate.
(112) SPARTAN Vers. 5.0.1, Wavefunction Inc., Irvine, USA.
(113) Perrin, D.D.; Armarego, W.L.F.: Purification of Laboratory Chemicals, 3rded, Pergamon Press, Oxford, 1988, 57-371.
(114) Fox, H.H.: Synthetic tuberculostats. II. Amino- and hydroxy-pyridin carboxylic acid derivatives. J. Org. Chem. 1952, 17, 547-554.
(115) Hou, G.; Gravier, D.; Casadebaig, F.; Dupin, J.-P.; Bernard, H.; Boisseau, M.: Pyrido[2,3-d]pyrimidin-4(3H)-one derivatives and 1,2,3,4-tetrahydro-pyrido[2,3-d]pyrimidine derivatives: Synthesis and in vitro study of their activity against platelet aggregation. Pharmazie 1995, 50, 719-722.
(116) Philips, A.: Untersuchungen in der Pyridinreihe. Liebigs Ann. Chem. 1895, 288, 253-265.
(117) Crum, J.D.; Fuchsman, C.H.: The chemistry of heterocycles. IV. 2H-Pyrido[4,3-e]-1,3-oxazine-2,4(3H)-dione, its precursors and some 3-substituted derivatives. J. Heterocycl. Chem. 1966, 3, 252-256.
(118) Spiessens, L.I.M.; Anteunis, M.J.O.: Preparation and structural assignments of some isomeric 2,3-disubstituted pyridines. Bull. Soc. Chim. Belg. 1980, 89, 205-231.
(119) Kirpal, A.: Über den Abbau des Chinolinsäure-b-Esters. Monatsh. 1908, 29, 227-231.
(120) Meijer, L.; Borgne, A.; Mulner, O.; Chong, J.P.J.; Blow, J.J.; Inagaki, N.; Inagaki, M.; Delcros, J.-G.; Moulinoux, J.-P.: Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. Eur. J. Biochem. 1997, 243, 527-536.
(121) Lew, J.; Beaudette, K.; Litwin, C.M.E.; Wang, J.H.: Purification and characterization of a novel proline-directed protein kinase from bovine brain. J. Biol. Chem. 1992, 267, 13383-13390.