Structural analogues of the calanolide anti-HIV agents. Modification of the trans-10,11-dimethyldihydropyran-12-ol ring (ring C)

Journal of Medicinal Chemistry

Volumn 40, Issue 6, 1997, Pages 1005-1017

  Zembower, David E ^a   Liao, Shuyuan ^a   Flavin, Michael T ^a   Xu, Ze Qi ^a   Stup, Tracy L ^b   Buckheit Jr , Robert W ^b   Khilevich, Albert ^a   Mar, Aye Aye ^a   Sheinkman, Abram K ^a  

^a MediChem Research Inc   (United States)

^b Virology Research Division   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CALANOLIDE A; CALANOLIDE DERIVATIVE; RNA DIRECTED DNA POLYMERASE INHIBITOR; UNCLASSIFIED DRUG;

ANTIVIRAL ACTIVITY; ARTICLE; CELL PROTECTION; CONTROLLED STUDY; DRUG ISOLATION; DRUG SYNTHESIS; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION;

ANTI-HIV AGENTS; CELL SURVIVAL; COUMARINS; HIV-1; HIV-1 REVERSE TRANSCRIPTASE; HUMANS; MAGNETIC RESONANCE SPECTROSCOPY; MOLECULAR STRUCTURE; PYRANOCOUMARINS; REVERSE TRANSCRIPTASE INHIBITORS; TUMOR CELLS, CULTURED;

EID: 0030892239     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm960355m     Document Type: Article

References (34)

1. This material was presented at the 25th National Medicinal Chemistry Symposium of the American Chemical Society, Ann Arbor, MI, June 15-18, 1996; abstract no. 32.
2. Barre-Sinoussi, F.; Chermann, J. C.; Rey, F.; Chamaret, M. T.; Gruest, J.; Dauguet, C.; Axler-Blin, C.; Veinet-Brun, F.; Rouzioux, C.; Rosenbaum, W.; Montagnier, L. Isolation of a T-lymphotropic Retrovirus from a Patient at Risk for Acquired Immune Deficiency Syndrome (AIDS). Science 1983, 220, 868-870.
3. Gottlieb, M. S.; Schroff, R.; Schanker, H. M.; Weisman, J. D.; Fan, P. T.; Wolf, R. A.; Saxon, A. Pnemocystis carinii Pneumonia and Mucosal Candidiasis in Previously Healthy Homesexual Men: Evidence of a New Acquired Cellular Immunodeficiency. N. Engl. J. Med. 1981, 305, 1425-1431.
4. Pinner, R. W.; Teutsch, S. M.; Simonsen, L.; Klug, L. A.; Graber, J. M.; Clarke, M. A.; Berkelman, R. L. Trends in Infectious Diseases Mortality in the United States. J. Am. Med. Assoc. 1996, 275, 189-193.
5. Hu, D. J.; Dondero, T. J.; Rayfield, M. A.; George, J. R.; Schochetman, G.; Jaffe, H. W.; Luo, C.-C.; Kalish, M. L.; Weniger, B. G.; Pau, C.-P.; Schable, C. A.; Curran, J. W. The Emerging Genetic Diversity of HIV. J. Am. Med. Assoc. 1996, 275, 210-216.
6. Spence, R. A.; Anderson, K. S.; Johnson, K. A. HIV-1 Reverse Transcriptase Resistance to Nonnucleoside Inhibitors. Biochemistry 1996, 35, 1054-1063.
7. Larder, B. A. Interaction Between Drug Resistant Mutations in Human Immunodeficiency Virus Type 1 Reverse Transcriptase. J. Gen. Virol. 1994, 75, 951-957.
8. Cox, S. W.; Aperia, K.; Sandstrom, E.; Holmberg, V.; Morfeldt-Manson, L.; Brostrom, C.; Wahren, B.; Albert, J. Cross-resistance Between AZT, ddI and Other Antiretroviral Drugs in Primary Isolates of HIV-1. Antiviral Chem. Chemother. 1994, 5, 7-12.
9. Mellors, J. W.; Larder, B. A.; Shinazi, R. F. Mutations in HIV-1 Reverse Transcriptase and Protease Associated with Drug Resistance. Int. Antiviral News 1995, 3, 8-13.
10. De Clercq, E. Toward Improved Anti-HIV Chemotherapy: Therapeutic Strategies for Intervention with HIV Infections. J. Med. Chem. 1995, 38, 2491-2517.
11. Young, S. D. Non-nucleoside Inhibitors of HIV-1 Reverse Transcriptase. Persp. Drug Disc. Des. 1993, 1, 181-192.
12. Larder, B. A.; Kemp, S. D.; Harrigan, P. R. Potential Mechanism for Sustained Antiretroviral Efficacy of AZT-3TC Combination Therapy. Science 1995, 269, 696-699.
13. Buckheit, R. W., Jr.; Fliakas-Boltz, V.; Decker, W. D.; Roberson, J. L.; Pyle, C. A.; White, E. L.; Bowdon, B. J.; McMahon, J. B.; Boyd, M. R.; Bader, J. P.; Nickell, D. G.; Barth, H.; Antonucci, T. K. Biological and Biochemical Anti-HIV Activity of the Benzothiadiazine Class of Nonnucleoside Reverse Transcriptase Inhibitors. Antiviral Res. 1994, 25, 43-56.
14. Buckheit, R. W., Jr.; Hollingshead, M. G.; Germany-Decker, J.; White, E. L.; McMahon, J. B.; Allen, L. B.; Ross, L. J.; Decker, W. D.; Westbrook, L.; Shannon, W. M.; Weislow, O.; Bader, J. P.; Boyd, M. R. Thiazolobenzimidazole: Biological and Biochemical Anti-retroviral Activity of a New Nonnueleoside Reverse Transcriptase Inhibitor. Antiviral Res. 1993, 21, 247-265.
15. Kashman, Y.; Gustafson, K. R.; Fuller, R. W.; Cardellina, J. H., II; McMahon, J. B.; Currens, M. J.; Buckheit, R. W., Jr.; Hughes, S. H.; Cragg, G. M.; Boyd, M. R. The Calanolides, a Novel HIV-Inhibitory Class of Coumarin Derivatives from the Tropical Rainforest Tree, Calophyllum lanigerum. J. Med. Chem. 1992, 35, 2735-2743.
16. Patil, A. D.; Freyer, A. J.; Eggleston, D. S.; Haltwanger, R. C.; Bean, M. F.; Taylor, P. B.; Caranfa, M. J.; Breen, A. L.; Bartus, H. R.; Johnson, R. K.; Hertzberg, R. P.; Westley, J. W. The Inophyllums, Novel Inhibitors of HIV-1 Reverse Transcriptase Isolated from the Malaysian Tree, Calophyllum inophyllum Linn. J. Med. Chem. 1993, 36, 4131-4138.
17. Cardellina, J. H., II; Bokesch, H. R.; McKee, T. C.; Boyd, M. R. Resolution and Comparative Anti-HIV Evaluation of the Enantiomers of Calanolides A and B. Bioorg. Med. Chem. Lett. 1995, 5, 1011-1014.
18. Kucherenko, A.; Flavin, M. T.; Boulanger, W. A.; Khilevich, A.; Shone, R. L.; Rizzo, J. D.; Sheinkman, A. K.; Xu, Z.-Q. Novel Approach for Synthesis of (±)-Calanolide A and its Anti-HIV Activity. Tetrahedron Lett. 1995, 36, 5475-5478.
19. Flavin, M. T.; Rizzo, J. D.; Khilevich, A.; Kucherenko, A.; Sheinkman, A. K.; Vilaychack, V.; Lin, L.; Chen, W.; Greenwood, E. M.; Pengsuparp, T.; Pezzuto, J. M.; Hughes, S. H.; Flavin, T. M.; Cibulski, M.; Boulanger, W. A.; Shone, R. L.; Xu, Z.-Q. Synthesis, Chromatographic Resolution, and Anti-Human Immunodeficiency Virus Activity of (±)-Calanolide A and its Enantiomers. J. Med. Chem. 1996, 39, 1303-1313.
20. Chenera, B.; West, M. L.; Finkelstein, J. A.; Dreyer, G. B. Total Synthesis of (±)-Calanolide A, a Non-Nucleoside Inhibitor of HIV-1 Reverse Transcriptase. J. Org. Chem. 1993, 58, 5605-5606.
21. Palmer, C. J.; Josephs, J. L. Synthesis of the Calophyllum Coumarins. Tetrahedron Lett. 1994, 35, 5363-5366.
22. Palmer, C. J.; Josephs, J. L. Synthesis of the Calophyllum Coumarins. Part 2. J. Chem. Soc., Perhin Trans. 1 1995, 3135-3151.
23. For purposes of simplicity, we refer to the coumarin ring comprising ring positions 1-4 as ring A, the pyran ring comprising ring positions 5-8 as ring B, and the dihydropyran ring comprising ring positions 9-12 as ring C.
24. Rao, A. V. R.; Gaitonde, A. S.; Prakash, K. R. C.; Rao, S. P. A Concise Synthesis of Chiral 2-Methyl Chroman-4-ones: Stereoselective Build-Up of the Chromanol Moiety of Anti-HIV Agent, Calanolide A. Tetrahedron Lett. 1994, 35, 6347-6350.
25. Deshpande, P. P.; Baker, D. C. A Simple Approach to the Synthesis of the Chiral Substituted Chroman Ring of Calophyllum Coumarins. Synthesis 1996, 630-632.
26. Deshpande, P. P.; Tagliaferri, F.; Victory, S. F.; Yan, S.; Baker, D. C. Synthesis of Optically Active Calanolides A and B. J. Org. Chem. 1995, 60, 2964-2965.
27. Khilevich, A.; Rizzo, J. D.; Flavin, M. T.; Sheinkman, A. K.; Mar, A.; Kucherenko, A.; Yan, C.; Dzekhtser, S.; Brankovic, D.; Lin, L.; Liu, J.; Rizzo, T. M.; Xu, Z.-Q. A Versatile Approach for Synthesis of 2,3-Dimethyl Chroman-4-ones, Intermediates for Calanolide Anti-HIV Agents, via Aldol/Mitsunobu Reactions. Synth. Commun. 1996, 20, 3757-3771.
28. Crombie, L.; Jones, R. C. F.; Palmer, C. J. Synthesis of the Mammea Coumarins. Part 1. The Coumarins of the Mammea A, B, and C Series. J. Chem. Soc., Perkin Trans. 1 1987, 317-331.
29. Gemal, A. L.; Luche, J.-L. Lanthanoids in Organic Synthesis. 6. The Reduction of α-Enones by Sodium Borohydride in the Presence of Lanthanoid Chlorides: Synthetic and Mechanistic Aspects. J. Am. Chem. Soc. 1981, 103, 5454-5459.
30. McKee, T. C.; Cardellina, J. H., II; Dreyer, G. B.; Boyd, M. R. The Pseudocalanolides: Structure Revision of Calanolides C and D. J. Nat. Prod. 1995, 58, 916-920.
31. Anastasis, P.; Brown, P. E. Studies of Chromens. Part 2. Synthesis of 7-Methoxy-2,2-dimethylchromen-3-carboxylic Acid. J. Chem. Soc., Perkin Trans. 1 1983, 197-200.
32. Boyer, P. L.; Currens, M. J.; McMahon, J. B.; Boyd, M. R.; Hughes, S. H. Analysis of Nonnucleoside Drug-Resistant Variants of Human Immunodeficiency Virus Type 1 Reverse Transcriptase. J. Virol. 1993, 67, 2412-2420.
33. Patil, A. D.; Hertzberg, R. P.; Dreyer, G. B.; Freyer, A. J.; Westley, J. W.; Chenera, B.; West, M. L. Coumarin Derivatives as Retroviral Inhibitors. PCT Int. Appl. WO 94 14,789, 1994; Chem. Abstr. 1994, 121, 170524h.
34. During preparation of the revised version of this paper, other investigators reported the anti-HIV activity of ketone 5: Galinis, D. L.; Fuller, R. W.; McKee, T. C.; Cardellina, J. H.; Gulakowski, R. J.; McMahon, J. B.; Boyd, M. R. Structure-Activity Modifications of the HIV-1 Inhibitors (+)-Calanolide A and (-)-Calanolide B. J. Med. Chem. 1996, 39, 4507-4510.