Inhibitors of Protein Kinase C. 2. Substituted Bisindolylmaleimides with Improved Potency and Selectivity

Journal of Medicinal Chemistry

Volumn 35, Issue 6, 1992, Pages 994-1001

  Davis, Peter D ^a   Elliott, Lucy H ^a   Harris, William ^a   Hill, Christopher H ^a   Hurst, Steven A ^a   Keech, Elizabeth ^a   Kumar, M K Hari ^a   Lawton, Geoffrey ^a   Nixon, John S ^a   Wilkinson, Sandra E ^a  

^a ROCHE PRODUCTS LTD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ACETIC ANHYDRIDE; CYCLIC AMP DEPENDENT PROTEIN KINASE; ETHYLENE OXIDE; MALEIMIDE DERIVATIVE; PROTEIN KINASE C; STAUROSPORINE;

ABSORPTION; ALKYLATION; ANIMAL EXPERIMENT; ARTICLE; AUTOIMMUNITY; CHROMATOGRAPHY; COMPETITIVE INHIBITION; CRYSTAL STRUCTURE; DIAGNOSIS; DRUG POTENCY; ENZYME INHIBITION; FEMALE; IMMUNOSUPPRESSIVE TREATMENT; MIXED LYMPHOCYTE REACTION; NONHUMAN; ORAL DRUG ADMINISTRATION; PRIORITY JOURNAL; RAT; SEQUENCE HOMOLOGY; SIGNAL TRANSDUCTION; SPECTROMETRY; STRUCTURE ACTIVITY RELATION;

ANIMAL; CATTLE; FEMALE; HUMAN; MALEIMIDES; MODELS, MOLECULAR; PROTEIN KINASE C; RATS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0026538078     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm00084a004     Document Type: Article

References (26)

1. Farago, A.; Nishizuka, Y. Protein Kinase C in Transmembrane Signalling. FEBS Lett. 1990, 268, 350-354.
2. Tritton, T. R.; Hickman, J. A. How to kill Cancer Cells: Membranes and Cell Signalling as Targets in Cancer Chemotherapy. Cancer Cells 1990, 2, 95-105.
3. Garland, L. G. Is There a Biochemical Lesion in Intrinsic Asthma? Agents Actions Suppl. 1989, 28, 135-145.
4. Jakobovits, A.; Rosenthal, A.; Capon, D. J. Trans-activation of HIV-1 LTR-directed Gene Expression by TAT Requires Protein Kinase C. EMBO J. 1990, 9, 1165-1170.
5. Murakawa, K.; Kohno, M.; Yasunari, K.; Hono, T.; Takeda, T. Possible Involvement of Protein Kinase C in the Maintainance of Hypertension in Spontaneously Hypertensive Rats. J. Hypertens. Suppl. 1988, 6, S157-S159
6. Nagao, S.; Seishima, M.; Mori, S.; Nozawa, Y. Increased Protein Kinase C Activity in Fibroblast Membranes from Psoriatic Patients. J. Invest. Dermatol. 1988, 90, 406-408.
7. Berry, N.; Nishizuka, Y. Protein Kinase C and T Cell Activation. Eur. J. Biochem. 1990, 189, 205-214.
8. Davis, P. D.; Hill, C. H.; Lawton, G.; Nixon, J. S.; Wilkinson, S. E.; Hurst, S. A.; Keech, E.; Turner, S. E. Inhibitors of Protein Kinase C (1): 2,3-Bisarylmaleimides. J. Med. Chem. 1992, 35, 177-184
9. Meyer, T.; Reganass, U.; Fabbro, D.; Alteri, E.; Rosel, J.; Muller, M.; Caravatti, G.; Matter, M. A Derivative of Staurosporine (CGP 41 251) shows Selectivity for Protein Kinase C Inhibition and In Vitro Anti-proliferative Aswell as In Vivo Anti-tumor Activity. Int. J. Cancer 1989, 43, 851-856.
10. Osada, H.; Takahashi, H.; Tsunoda, H.; Kusakabe, H.; Isono, K. A New Inhibitor of Protein Kinase C, RK-286C (4'-Demethylamino-4'-hydroxystaurosporine). J. Antibiotics 1990, 43, 163-167.
11. Gross, J. L.; Herblin, W.; Do, U. H.; Pounds, S. P.; Buenaga, L. J.; Stephens, L. E. Characterisation of Specific [3H]Dimethylstaurosporine Binding to Protein Kinase C. Biochem. Pharmacol. 1990, 40, 343-350.
12. Davis, P. D.; Hill, C. H.; Thomas, W. A.; Whitcombe, I. W. A. The Design of Inhibitors of Protein Kinase C: The Solution Conformation of Staurosporine. J. Chem. Soc., Chem. Commun. 1991, 182-184
13. Davis, P. D.; Bit, R. A.; Hurst, S. A. A Convenient Synthesis of Bisindolyl-and Indolylaryl-maleic Anhydrides. Tetrahedron Lett. 1990, 31, 2353-2356
14. Sapse, A. M.; Russell, C. S. Theoretical Studies of the Binding of Methylamine and Guanidine to Carboxylate. J. Mol. Struct. (Theochem) 1986, 137, 43-53
15. Fersht, A. Enzyme Structure and Mechanism, 2nd ed.; W. H. Freeman: New York, 1985; Chapter 11.
16. Rebek, J. Model Studies in Molecular Recognition. Science 1987, 235, 1478-1484.
17. Agranat, I.; Riggs, N. V.; Radom, L. The Formamidine-Formic Acid Dimer: A Theoretical Examination of its Equilibrium Structure and of the Double-Proton-Transfer Process. J. Chem. Soc., Chem. Commun. 1991, 80-81
18. Perrin, D. D. Dissociation Constants of Organic Bases in Aqueous Solution; Butterworths: London, 1965; p 446.
19. Young, R. C.; Durant, G. J.; Emmett, J. C.; Ganellin, C. R.; Graham, M. J.; Mitchell, R. C.; Prain, D. H.; Roantree, M. L. Dipole Moment in Relation to H2 Receptor Histamine Antagonist Activity for Cimetidine Analogues. J. Med. Chem. 1986, 29, 44-49
20. Spacey, G. D.; Bonser, R. W.; Randall, R. W.; Garland, L. G. Selectivity of Protein Kinase Inhibitors in Human Intact Platelets. Cell. Signaling 1990, 2, 329-338.
21. Davis, P. D.; Hill, C. H.; Keech, E.; Lawton, G.; Nixon, J. S.; Sedgwick, A. D.; Wadsworth, J.; Westmacott, D.; Wilkinson, S. E. Potent Selective Inhibitors of Protein Kinase C. FEBS Lett. 1989, 259, 61-63
22. Hanks, S. K.; Quinn, A.; Hunter, T. The Protein Kinase C Family: Conserved Features and Deduced Phylogeny of the Catalytic Domains. Science 1988, 241, 42-52.
23. Elliott, L. H.; Wilkinson, S. E.; Sedgwick, A. D.; Hill, C. H.; Lawton, G.; Davis, P. D.; Nixon, J. S. K252a is a Potent and Selective Inhibitor of Phosphorylase Kinase. Biochem. Biophys. Res. Commun. 1990, 171, 148-154.
24. Bach, F.; Hirschhorn, K. Lymophocyte Interaction. A Potential Histocompatability Test In Vitro. Science 1964, 143, 813-817
25. Gerber, P. R.; Gubernator, K.; Mueller, K. Generic Shapes for the Conformation Analysis of Macrocyclic Structures. Helv. Chim. Acta 1988, 71, 1429-1441
26. Fitzharris, P.; Knight, R. A. Generation of Suppressor Cells in the Autologous Mixed Lymphocyte Reaction. Clin. Exp. Immunol. 1981, 46, 185-195