Synthesis and antitumor activity of 4-aminomethylthioxanthenone and 5- aminomethylbenzothiopyranoindazole derivatives

Journal of Medicinal Chemistry

Volumn 41, Issue 19, 1998, Pages 3645-3654

  Perni, Robert B ^a,d   Wentland, Mark P ^a,e   Huang, Jianhua I ^a   Powles, Ronald G ^a   Aldous, Suzanne ^a   Klingbeil, Kristina M ^a   Peverly, A Danielle ^a   Robinson, Ronald G ^a   Corbett, Thomas H ^b   Jones, Julie L ^b   Mattes, Kenneth C ^c   Rake, James B ^a   Coughlin, Susan A ^a  

^a Sanofi Winthrop Inc   (United States)

^b WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c EASTMAN KODAK COMPANY   (United States)

^d VERTEX PHARMACEUTICALS   (United States)

^e Research Rensselaer Polytechnic Institute   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DNA TOPOISOMERASE INHIBITOR; INDAZOLE DERIVATIVE; THIOXANTHENE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CHEMICAL ANALYSIS; CHEMICAL MODIFICATION; CYTOTOXICITY TEST; DRUG CYTOTOXICITY; DRUG DNA BINDING; DRUG SYNTHESIS; ENZYME INHIBITION; MOUSE; NONHUMAN;

ADENOCARCINOMA; ANIMALS; ANTINEOPLASTIC AGENTS; DNA TOPOISOMERASES, TYPE II; DNA, NEOPLASM; DRUG SCREENING ASSAYS, ANTITUMOR; ENZYME INHIBITORS; HUMANS; INDAZOLES; INTERCALATING AGENTS; LEUKEMIA P388; MICE; NEOPLASM TRANSPLANTATION; PANCREATIC NEOPLASMS; PYRANS; STRUCTURE-ACTIVITY RELATIONSHIP; THIOXANTHENES; TUMOR CELLS, CULTURED;

EID: 15144340193     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm9708083     Document Type: Article

References (28)

1. (a) Beardsley, T. Trends in Cancer Epidemiology-A War Not Won. Sci. Am. 1994, 130-138.
2. (b) Oldhan, R. K. Cancer Research: Does it Deliver for the Patient. Cancer Biother. 1994, 9, 99-102.
3. (a) Corbett, T. H.; Valeriote, F. A.; Polin, L.; Panchapor, C.; Pugh, S.; White, K.; Lowichik, N.; Knight, J.; Bissery, M.-C.; Wozniak, A.; LoRusso, P.; Biernat, L.; Polin D.; Knight, L.; Biggar, S.; Looney, D.; Demchik, L.; Jones, J.; Jones, L.; Blair, S.; Palmer, K.; Essenmacher, S.; Lisow, L.; Mattes, K. C.; Cavanaugh, P. F.; Rake, J. B.; Baker, L. In Cytotoxic Anticancer Drugs: Models and Concepts for Drug Discovery and Development; Valeriote, F. A., Corbett, T. H., Baker, L. H., Eds.; Kluwer Academic Publishers: Boston, 1992; pp 35-87.
4. (b) Corbett, T. H.; Roberts, B. J.; Leopold, W. R.; Peckham, J. C.; Wilkoff, L. J.; Griswold, D. P., Jr.; Schabel, F. M., Jr. Induction and Chemotherapeutic Response of Two Transplantable Ductal Adenocarcinoma of the Pancreas in C57BL/6 Mice. Cancer Res. 1984, 44, 717-726.
5. (c) LoRusso, P.; Wozniak, A. J.; Polin, L.; Capps, D.; Leopold, W. R.; Werbel, L. M.; Biernat, L.; Dan, M. E.; Corbett, T. H. Antitumor Efficacy of PD115934 (NSC 366140) against Solid Tumor of Mice. Cancer Res. 1990, 50, 4900-4905.
6. Wentland, M. P.; Perni, R. B.; Powles, R. G.; Hlavac, A. G.; Mattes, K. C.; Corbett, T. H.; Coughlin, S. A.; Rake, J. B. Anti-Solid Tumor Efficacy and Preparation of N-[[1-[[2-(Diethylamino)ethyl]amino]-9-oxo-9H-thioxantheN-4-yl]methyl]methane- sulfonamide (WIN 33377) and Related Derivatives. Bioorg. Med. Chem. Lett. 1994, 4, 609-614.
7. (a) Archer, S.; Pica-Mattoccia, L.; Cioli, D.; Seyed-Mozaffari, A.; Zayed, A.-H. Preparation and Antischistosomal and Antitumor Activity of Hycanthone and Some of its Congeners. Evidence for Mode of Action of Hycanthone. J. Med. Chem. 1988, 31, 254-260.
8. (b) Archer, S.; Zayed, A.-H.; Rej, R.; Rugino, T. A. Analogues of Hycanthone and Lucanthone as Antitumor Agents. J. Med. Chem. 1983, 26, 1240-1246.
9. For a preliminary account of this work see: (a) Wentland, M. P.; Perni, R. B.; Huang, J. L; Powles, R. G.; Aldous, S. A.; Klingbeil, K. M.; Peverly, A. D.; Robinson, R. G.; Corbett, T. H.; Rake, J. B.; Coughlin, S. A. Thioxanthone antitumor agents: effects of variation of the 1- and 9-positions of Win 33377 on antitumor activity. Proceedings of the Eighty-sixth Annual Meeting of the American Association for Cancer Research, Toronto, Canada, March 18-22, 1995; Abstr. 2289. (b) Wentland, M. P.; Perni, R. B.; Huang, J. I.; Powles, R. G.; Aldous, S. A.; Klingbeil, K. M.; Peverly, A. D.; Robinson, R. G.; Corbett, T. H.; Jones, J. L.; Rake, J. B.; Coughlin, S. A. Cyclic Variations of SR 233377 (WIN 33377) and Effects on Antitumor Activity. Bioorg. Med. Chem. Lett. 1996, 6, 1345-1350.
10. For a preliminary account of this work see: (a) Wentland, M. P.; Perni, R. B.; Huang, J. L; Powles, R. G.; Aldous, S. A.; Klingbeil, K. M.; Peverly, A. D.; Robinson, R. G.; Corbett, T. H.; Rake, J. B.; Coughlin, S. A. Thioxanthone antitumor agents: effects of variation of the 1- and 9-positions of Win 33377 on antitumor activity. Proceedings of the Eighty-sixth Annual Meeting of the American Association for Cancer Research, Toronto, Canada, March 18-22, 1995; Abstr. 2289. (b) Wentland, M. P.; Perni, R. B.; Huang, J. I.; Powles, R. G.; Aldous, S. A.; Klingbeil, K. M.; Peverly, A. D.; Robinson, R. G.; Corbett, T. H.; Jones, J. L.; Rake, J. B.; Coughlin, S. A. Cyclic Variations of SR 233377 (WIN 33377) and Effects on Antitumor Activity. Bioorg. Med. Chem. Lett. 1996, 6, 1345-1350.
11. Showalter, H. D. H.; Angelo, M. M.; Berman, E. M.; Kanter, G. D.; Ortwine, D. F.; Ross-Kesten, S. G.; Surcel, A. D.; Turner, W. R.; Werbel, L. M.; Worth, D. F.; Elslager, E. F.; Leopold, W. R.; Shillis, J. L. Benzothiopyranoindazoles, a New Class of Chromophore Modified Anthracenedione Anticancer Agents. Synthesis and Activity against Murine Leukemias. J. Med. Chem. 1988, 31, 1527-1539.
12. Capps, D. B.; Dunbar, J.; Kesten, S. R.; Shillis, J.; Werbel, L. M.; Plowman, J.; Ward, D. L. 2-(Aminoalkyl)-5-nitropyrazolo-[3,4,5-kl]acridines, a New Class of Anticancer Agents. J. Med. Chem. 1992, 35, 4770-4778.
13. Sebolt, J. S.; Scavone, S. V.; Pinter, C. D.; Hamelehle, K. L.; Von Hoff, D. D.; Jackson, R. C. Pyrazolacridines, a New Class of Anticancer Agents with Selectivity Against Solid Tumors in Vitro. Cancer Res. 1987, 47, 4299-4304.
14. Rosi, D.; Peruzzotti, G.; Dennis, E. W.; Berberian, D. A.; Freele, H.; Tullar, B. F.; Archer, S. Hycanthone, a New Active Metabolite of Lucanthone. J. Med. Chem. 1967, 10, 867-876.
15. Laidlaw, G. M.; Collins, J. C.; Archer, S.; Rosi, D.; Schulenberg, J. W. The Synthesis of Hycanthone. J. Org. Chem. 1973, 38, 1743-1746.
16. Elslager, E. F.; Weinstein, E. A.; Worth, D. F. Synthesis and Biological Properties of Aminoalkylhydrazines. A Unique Nitrogen-Nitrogen Scission of 1-(2-Diethylaminoethyl)-2-(1-phenyl-2-propyl)hydrazine. J. Med. Chem. 1964, 7, 493-500.
17. Rieche, A.; Gross, H.; Höft, E. Syntheses of Aromatic Aldehydes with Dichloromethyl-alkylethers. Chem. Ber. 1960, 93, 88-94.
18. Nabih, I.; Elsheikh, M. Chlorination and Condensation Reactions at the 4-Methyl Group of Lucanthone and Oxalucanthone. J. Pharm. Sci. 1965, 54, 1672-1673.
19. Ruckdeschel, J. C.; Modi, S. P.; El-Hamouly, W.; Portuese, E.; Archer, S. N-Methylcarbamate Derivatives of Ellipticine and Olivacine with Cytotoxic Activity against Four Human Lung Cancer Cell Lines. J. Med. Chem. 1992, 35, 4854-4857.
20. (a) Le Pecq, J.-B.; Dat-Xuong, N.; Gosse, C.; Paoletti, C. A New Antitumoral Agent: 9-Hydroxyellipticine. Possibility of a Rational Design of Anticancerous Drugs in the Series of DNA Intercalating Drugs. Proc. Natl. Acad. Sci. U.S.A. 1974, 71, 5078-5082.
21. (b) LoRusso, P. M.; Demchick, L. L.; Mondesir, J. M.; Azab, M.; Blair, S.; Knight, J.; Corbett, T. H. Preclinical antitumor activity of SR26050. Proceedings of the Eighty-third Annual Meeting of American Association for Cancer Research, San Diego, CA, May 20-23, 1992; Abstr. 3118.
22. (c) LoRusso, P.; Mucci, P.; Biernat, L.; Mondesir, J. M.; Gros, P.; Corbett, T. Antitumor efficacy of SR95325B against murine tumor models. Proceedings of the Eighty-second Annual Meeting of American Association for Cancer Research, Houston, TX, May 15-18, 1991; Abstr. 2417.
23. Coughlin, S. C.; Danz, D. W.; Robinson, R. G.; Klingbeil, K. M.; Wentland, M. P.; Corbett, T. H.; Waud, W. R.; Zwelling, L. A.; Altschuler, E.; Bales, E.; Rake, J. B. Mechanism of Action and Antitumor Activity of (S)-10-(2,6-Dimethyl-4-pyridinyl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H- pyrido[1,2,3-de][1,4]benzothiazine-6-carboxylic Acid (WIN 58161). Biochem. Pharmacol. 1995, 50, 111-122.
24. Cain, B. F.; Baguley, B. C.; Denny, W. A. Potential Antitumor Agents. 28. Deoxyribonucleic Acid Polyintercalating Agents. J. Med. Chem. 1978, 21, 658-668.
25. Hopfinger, J. A.; Kawakami, Y. QSAR Analysis of a set of benzothiopyranoindazole anti-cancer analogues based upon their DNA intercalation properties as determined by molecular dynamics simulation. Anti-Cancer Drug Des. 1992, 7, 203-217.
26. Trask, D. K.; DiDonato, J. A.; Muller, M. T. Detection and Isolation of Covalent DNA/protein Complexes: Application to Topoisomerase I and II. EMBO J. 1984, 3, 671-676.
27. Pommier, Y.; Minford, J. K; Schwartz, R. E.; Zwelling, L. A.; Kohn, K. W. Effects of the DNA Intercalators 4′-(9-Acridinyl-amino)methansulfon-m-anisidide and 2-Methyl-9-hydroxyellipticinium on Topoisomerase II Mediated DNA Strand Cleavage and Strand Passage. Biochemistry 1985, 24, 6410-6416.
28. Corbett, T.; Lowichik, N.; Pugh, S.; Polin, L.; Panchapor, C.; White, K.; Knight, J.; Demchik, L.; Jones, J.; Jones, L.; Biernat, L.; LoRusso, P.; Foster, B.; Heilbnin, L.; Rake, J.; Mattes, K. C.; Perni, R.; Powles, R. G.; Hlavac, A. G.; Wentland, M. P.; Coughlin, S. A.; Baker, L.; Valeriote, F. Antitumor activity of N-[[1-[[2-(diethylamino)ethyl]amino]-9-oxo-9H-thioxanthen-4-yl]-methyl] methanesulfonamide (WIN 33377) and analogues. Exp. Opin. Invest. Drugs 1994, 3, 1281-1292.