Design, synthesis, and evaluation of 3,4-dihydro-2H-[1,4]diazepino[6,7,1- hi]indol-1-ones as inhibitors of poly(ADP-ribose) polymerase

Journal of Medicinal Chemistry

Volumn 47, Issue 22, 2004, Pages 5467-5481

  Tikhe, Jayashree G ^a   Webber, Stephen E ^b   Hostomsky, Zdenek ^a   Maegley, Karen A ^a   Ekkers, Anne ^a   Li, Jianke ^a   Yu, Xiao Hong ^a   Almassy, Robert J ^c   Kumpf, Robert A ^a   Boritzki, Theodore J ^a   Zhang, Cathy ^a   Calabrese, Chris R ^d   Curtin, Nicola J ^d   Kyle, Suzanne ^d   Thomas, Huw D ^d   Wang, Lan Zhen ^d   Calvert, A Hilary ^d   Golding, Bernard T ^d   Griffin, Roger J ^d   Newell, David R ^d  

^a PFIZER INC   (United States)

^b F HOFFMANN LA ROCHE LTD   (Switzerland)

^c Quorex Pharmaceuticals   (United States)

^d NEWCASTLE UNIVERSITY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

3,4 DIHYDRO 2H [1,4]DIAZEPINO[6,7,1 HI]INDOL 1 ONE DERIVATIVE; ANTINEOPLASTIC AGENT; NICOTINAMIDE ADENINE DINUCLEOTIDE; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR; TOPOTECAN; UNCLASSIFIED DRUG;

ARTICLE; CANCER INHIBITION; CRYSTAL STRUCTURE; DRUG CONFORMATION; DRUG DESIGN; DRUG POTENTIATION; DRUG SYNTHESIS; ENZYME INHIBITOR INTERACTION; HUMAN; HUMAN CELL; INHIBITION KINETICS; MOLECULAR MODEL; STRUCTURE ACTIVITY RELATION;

ANTINEOPLASTIC AGENTS; AZEPINES; CELL LINE, TUMOR; CELL PROLIFERATION; CRYSTALLOGRAPHY, X-RAY; DNA TOPOISOMERASES, TYPE I, EUKARYOTIC; DRUG DESIGN; DRUG RESISTANCE, NEOPLASM; DRUG SYNERGISM; HUMANS; INDOLES; MODELS, MOLECULAR; POLY(ADP-RIBOSE) POLYMERASES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 6044250300     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm030513r     Document Type: Article

References (51)

1. From DNA Damage and Stress Signaling to Cell Death: Poly ADP-Ribosylation Reactions; de Murcia, G., Shall, S., Eds; Oxford University Press: Oxford, United Kingdom, 2000; and references therein.
2. Cell Death: The Role of PARP; Szabo, C., Ed.; CRC Press: Boca Raton, FL, 2000; and references therein.
3. Ame, J. C.; Rolli, V.; Schreiber, V.; Niedergang, C.; Apiou, F.; Decker, P.; Muller, S.; Hoger, T.; Ménissier de Murcia, J.; de Murcia, G. PARP-2, a novel mammalian DNA damage-dependent poly (ADP-ribose) polymerase. J. Biol. Chem. 1999, 274, 17860-17868.
4. Johansson, M. A human poly (ADP-ribose) polymerase gene family (ADPRTL): cDNA cloning of two novel poly (ADP-ribose) polymerase homologues. Genomics 1999, 57, 442-445.
5. Kickhoefer, V. A.; Siva, A. C.; Kedersha, N. L.; Inman, E. M.; Ruland, C.; Streuli, M.; Rome, L. H. The 193-kD vault protein, VPARP, is a novel poly (ADP-ribose) polymerase. J. Cell Biol. 1999, 146, 917-928.
6. Smith, S.; Girat, I.; Schmitt, A.; De Lange, T. Tankyrase, a poly (ADP-ribose) polymerase at human telomeres. Science 1998, 282, 1484-1487.
7. de Murcia, G.; Ménissier de Murcia, J. Poly (ADP-ribose) polymerase: A molecular nick-sensor. TIBS 1994, 19, 172-176.
8. Benjamin, R. C.; Gill, D. M. Poly (ADP-ribose) synthesis in vitro programmed by damaged DNA. J. Biol. Chem. 1981, 255, 10502-10508.
9. Satoh, M.; Lindahl, T. Role of poly (ADP-ribose) formation in DNA repair. Nature 1992, 356, 356-358.
10. Pieper, A. A.; Verma, A.; Zhang, J.; Snyder, S. H. Poly (ADP-ribose) polymerase, nitric oxide and cell death. TIPS 1999, 20, 171-181.
11. D'Amours, D.; Desnoyers, S.; D'Silva, I.; Poirier, G. G. Poly (ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem. J. 1999, 342, 249.
12. Lautier, D.; Lagueux, J.; Thibodeau, J.; Menard, L.; Poirier, G. G. Molecular and biochemical features of poly (ADP-ribose) metabolism. Mol. Cell. Biochem. 1993, 122, 171-193.
13. Lindahl, T.; Satoh, M. S.; Porier, G. G.; Klungland, A. Post-translational modification of poly (ADP-ribose) polymerase induced by DNA strand breaks. TIBS 1995, 20, 405-411.
14. Dantzer, F.; Schreiber, V.; Niedergang, C.; Trucco, C.; Flatter, E.; De La Rubia, G.; Pliver, J.; Rolli, V.; Ménissier de Murcia, J.; de Murcia, G. Involvement of poly (ADP-ribose) polymerase in base excision repair. Biochemie 1999, 81, 69-75.
15. Arundel-Suto, C. A.; Scavone, S. V.; Turner, W. R.; Suto, M. J.; Sebolt-Leopold, J. S. Effects of PD 128763, a new potent inhibitor of poly (ADP-ribose) polymerase, on X-ray-induced cellular recovery processes in Chinese hamster v79 cells. Radiat. Res. 1991, 126, 367-371.
16. Sheng, H.; Olive, P. L. Reduction of tumor hypoxia and inhibition of DNA repair by nicotinamide after irradiation of SCCVII murine tumor and normal tissue. Cancer Res. 1996, 56, 2801-2808.
17. Griffin, R. J.; Srinivasan, S.; Bowman, K.; Calvert, A. H.; Curtin, N. J.; Newell, D. R.; Pemberton, L. C.; Golding, B. T. Resistance-modifying agents. 5. Synthesis and biological properties of quinazoline inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP). J. Med. Chem. 1998, 41, 5247-5256.
18. Delaney, C. A.; Wang, L. Z.; Kyle, S.; White, A. W.; Calvert, A. H.; Curtin, N. J.; Durkacz, B. W.; Hostomsky, Z.; Newell, D. R. Potentiation of temozolomide and topotecan growth inhibition and cytotoxicity by novel poly(adenosine diphosphoribose) polymerase inhibitors in a panel of human tumor cell lines. Clin. Cancer Res. 2000, 6, 2860-2867.
19. Bowman, K. J.; Newell, D. R.; Calvert, A. H.; Curtin, N. J. Differential effects of the poly(ADP-ribose) polymerase (PARP) inhibitor NU1025 on topoisomerase I and II inhibitor cytotoxicity. Br. J. Cancer 2001, 84, 106-112.
20. Calabrese, C. R.; Almassy, R.; Barton, S.; Batey, M. A.; Boritzki, T.; Calvert, A. H.; Canan-Koch, S.; Durkacz, B. W.; Hostomsky, Z.; Kumpf, R. A.; Kyle, S.; Li, J.; Maegley, K.; Newell, D. R.; North, M.; Notarianni, E.; Stratford, I. J.; Skalitzky, D.; Thomas, H. D.; Wang, L.-Z.; Webber, S. E.; Williams, K. J.; Curtin, N. J. Anticancer chemo- and radio-sensitization in vitro and in vivo by a potent novel poly(ADP-ribose) polymerase inhibitor, AG14361. J. Natl. Can. Inst. 2004, 96, 56-67.
21. Tentori, L.; Portarena, I.; Graziani, G. Potential clinical applications of poly(ADP-ribose) polymerase (PARP) inhibitors. Pharmacol. Res. 2002, 45, 73-85.
22. Zhang, J. PARP inhibition: A novel approach to treat ischemia/ reperfusion and inflammation-related injuries. Emerging Drugs 1999, 4, 209-221 and references therein.
23. Szabó, C.; Dawson, V. L. Role of poly(ADP-ribose) synthetase in inflammation and ischemia-reperfusion. TIPS 1998, 19, 287-298.
24. Cosi, C.; Suzuki, H.; Skaper, S. D.; Milani, D.; Facci, L.; Menegazzi, M.; Vantini, G.; Kanai, Y.; Degryse, A.; Colpaert, F.; Koek, W.; Marien, M. R. Poly(ADP-ribose) polymerase (PARP) revisited. A new role for an old enzyme: PARP involvement in neurodegeneration and PARP inhibitors as possible neuroprotective agents. Ann. N. Y. Acad. Sci. 1997, 825 (Neuroprotective Agents), 366-379.
25. Szabá, C.; Virág, L.; Cuzzocrea, S.; Scott, G. S.; Hake, P.; O'Connor, M. P.; Zingarelli, B.; Salzman, A.; Kun, E. Protection against peroxy-nitrite-induced fibroblast injury and arthritis development by inhibition of poly(ADP-ribose) synthetase. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 3867-3872.
26. Purnell, M. R.; Whish, W. J. D. Novel inhibitors of poly(ADP-ribose) synthetase. Biochem. J. 1980, 185, 775-777.
27. Banasik, M.; Komura, H.; Shimoyama, M.; Ueda, K. Specific inhibitors of poly(ADP-ribose) synthetase and mono(ADP-ribosyltransferase. J. Biol. Chem. 1992, 267, 1569-1575.
28. Suto, M. J.; Turner, W. R.; Arundel-Suto, C. M.; Werbel, L. M.; Sebolt-Leopold, J. S. Dihydroisoquinolinones: The design and synthesis of a new series of potent inhibitors of poly(ADP-ribose) polymerase. Anti-Cancer Drug Des. 1991, 7, 107-117.
29. White, A. W.; Almassy, R.; Calvert, A. H.; Curtin, N. J.; Griffin, R. J.; Hostomsky, Z.; Maegley, K.; Newell, D. R.; Srinivasan, S.; Golding, B. T. Resistance-modifying agents. 9. Synthesis and biological properties of benzimidazole inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase. J. Med. Chem. 2000, 43, 4084-4097.
30. Canan Koch, S. S.; Thoresen, L. H.; Tikhe, J. G.; Maegley, K. A.; Almassy, R. J.; Li, J.; Yu, X.-H.; Zook, S. E.; Kumpf, R. A.; Zhang, C.; Boritzki, T. J.; Mansour, R. N.; Zhang, K. E.; Ekker, A.; Calabrese, C. R.; Curtin, N. J.; Kyle, S.; Thomas, H. D.; Wang, L.-Z.; Calvert, A. H.; Golding, B. T.; Griffin, R. J.; Newell, D. R.; Webber, S. E.; Hostomsky, Z. Novel tricyclic poly(ADP-ribose) polymerase-1 inhibitors with potent anticancer chemopotentiating activity: Design, synthesis, and X-ray cocrystal structure. J. Med. Chem. 2002, 45, 4961-4974.
31. Skalitzky, D. J.; Marakovits, J. T.; Maegley, K. A.; Ekker, A.; Yu, X.-H.; Hostomsky, Z.; Webber, S. E.; Eastman, B. W.; Almassy, R. J.; Li, J.; Curtin, N. J.; Newell, D. R.; Calvert, A. H.; Griffin, R. J.; Golding, B. T. Tricyclic benzimidazoles as potent PARP-1 inhibitors. J. Med. Chem. 2003, 46, 210-213.
32. Ruf, A.; Rolli, V.; de Murcia, G.; Schulz, G. E. The mechanism of the elongation and branching reaction of poly(ADP-ribose) polymerase as derived from crystal structures and mutagenesis. J. Mol. Biol. 1998, 278, 57-65.
33. Marsischky, G. T.; Wilson, B. A.; Collier, R. J. Role of glutamic acid 988 of human poly(ADP-ribose) polymerase in polymer formation. J. Biol. Chem. 1995, 270, 3247-3254.
34. Ruf, A.; de Murcia, J. M.; de Murcia, G. M.; Schulz, G. E. Structure of the catalytic fragment of poly(ADP-ribose) polymerase from chicken. Proc. Natl. Acad. Sci. U.S.A. 1998, 93, 7481-7485.
35. Chen, X.-Y.; Berti, P. J.; Schramm, V. L. Ricin A-chain: Kinetic isotope effect and transition state structure with stem-loop RNA. J. Am. Chem. Soc. 2000, 722, 1609-1617.
36. Han, S.; Craig, J. A.; Putnam, C. D.; Carozzi, N. B.; Tainer, J. A. Evolution and mechanism from structures of an ADP-ribosylating toxin and NAD complex. Nat. Struct. Biol. 1999, 6, 932-936.
37. + binding to poly(ADP-ribose) polymerase as derived from crystal structures and homology modeling. Biochemistry 1998, 37, 3893-3900.
38. Watson, C. Y.; Whish, W. J. D.; Threadgill, M. D. Synthesis of 3-substituted benzamides and 5-substituted isoquinolin-1-(2H)-ones and preliminary evaluation as inhibitors of poly(ADP-ribose) polymerase (PARP). Bioorg. Med. Chem. 1998, 6, 721-734.
39. In the human PARP-1 enzyme, amino acid 763 is a glutamic acid. See Computational Methods in the Experimental Section for details.
40. Hester, J.B.; Rudzik, A.D.; Veldkamp, W. Pyrrolo[3,2,1,-jk[1,4] benzodiazepines which have central nervous system activity. J. Med. Chem. 1970, 13, 827-835.
41. Miyaura, N.; Suzuki, A. Palladium-catalyzed cross-coupling reactions of organoboronic compounds. Chem. Rev. 1995, 95, 2457-2483.
42. Bradley, G.; Clark, J. 2,3-Dihydroqumolin-4(1H)-ones. Part I. Halogen-substituted 2,3-dihydroquinolin-4(1H)-ones and their 1-(2-acylethyl) derivatives. J. Chem. Soc., Perkins 1 1972, 2019-2023.
43. Eaton, P. E.; Carlson, G. R.; Lee, J. T. Phosphorous pentoxidemethanesulfonic acid. A convenient alternative to polyphosphoric acid. J. Org. Chem. 1973, 38, 4071-4073.
44. For a review of the Schmidt reaction, see Wolff, H. Organic Reactions; 1946; Vol. 3, Chapter 8, pp 307-336.
45. Taylor, E. C.; Katz, A. H.; Salgado-Zamora, H.; McKillop, A. Thallium in organic synthesis. 68. A convenient synthesis of 2-phenylindoles from anilides. Tetrahedron Lett. 1985, 26, 5963-5966.
46. Sakamoto, T.; Kondo, Y.; Yamanaka, H. Synthesis of condensed heteroaromatic compounds using palladium-catalyzed reaction, Heterocycles 1988, 27, 2225-2249.
47. Simonin, F.; Poch, O.; Delarue, M.; de Murcia, G. Identification of potential active-site residues in the human poly(ADP-ribose) polymerase. J. Biol. Chem. 1993, 268, 8529-8535.
48. Segel, I. H. Enzyme Kinetics: Behavior and Analysis of Rapid Equilibrium and Steady-State Enzyme Systems; John Wiley & Sons: New York, 1975; pp 100-125.
49. Sculley, M. J.; Morrison, J. F. The determination of kinetic constants governing the slow, tight-binding inhibition of enzyme-catalyzed reactions. Biochim. Biophys. Acta 1986, 874, 44-53.
50. Brunger, A. T.; Adams, P. D.; Clore, G. M.; DeLano, W. L.; Gros, P.; Grosse-Kunstleve, R. W.; Jiang, J. S.; Kuszewski, J.; Nilges, M.; Pannu, N. S.; Read, R. J.; Rice, L. M.; Simonson, T.; Warre, G. L. Crystallography and NMR system: A new software suite for macromolecular structure determination. Acta Crystallogr. D: Biol. Crystallogr. 1998, 54, 905-921.
51. Mohamadi, F.; Richards, N. G. J.; Guida, W. C.; Liskamp, R.; Lipton, M.; Caufield, C.; Chang, G.; Hendrickson, T.; Still, W. C. Macromodel V5.5; Macromodel-An integrated software system for modeling organic and bioorganic molecules using mechanics. J. Comput. Chem. 1990, 11, 440-467.