Quinolone 3-carboxylic acid pharmacophore: Design of second generation HIV-1 integrase inhibitors

Journal of Medicinal Chemistry

Volumn 51, Issue 5, 2008, Pages 1136-1144

  Dayam, Raveendra ^a,c   Al Mawsawi, Laith Q ^a   Zawahir, Zahrah ^a   Witvrouw, Myriam ^b   Debyser, Zeger ^b   Neamati, Nouri ^a  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^b UNIVERSITY OF LEUVEN   (Belgium)

^c GVK BIOSCIENCES PVT LTD   (India)

Author keywords

[No Author keywords available]

Indexed keywords

ELVITEGRAVIR; INTEGRASE INHIBITOR; QUINOLONE 3 CARBOXYLIC ACID; UNCLASSIFIED DRUG;

ARTICLE; CYTOTOXICITY; DRUG DETERMINATION; DRUG INHIBITION; DRUG STRUCTURE; HUMAN; HUMAN CELL; IN VITRO STUDY; PHARMACOPHORE;

ANIMALS; CARBOXYLIC ACIDS; CELL LINE; DATABASES, FACTUAL; DRUG DESIGN; HIV INTEGRASE; HIV INTEGRASE INHIBITORS; HIV-1; HUMANS; MICE; MODELS, MOLECULAR; MOLECULAR CONFORMATION; QUINOLONES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 41649096265     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm070609b     Document Type: Article

References (48)

1. Dieleman, J. P.; Jambroes, M.; Gyssens, I. C.; Sturkenboom, M. C.; Stricker, B. H.; Mulder, W. M.; de Wolf, F.; Weverling, G. J.; Lange, J. M.; Reiss, P.; Brinkman, K. Determinants of recurrent toxicity-driven switches of highly active antiretroviral therapy. The ATHENA cohort. AIDS 2002, 16 (5), 737-45.
2. Potter, S. J.; Dwyer, D. E.; Saksena, N. K. Differential cellular distribution of HIV-1 drug resistance in vivo: evidence for infection of CD8+ T cells during HAART. Virology 2003, 305 (2), 339-52.
3. Yusa, K.; Harada, S. Acquisition of multi-PI (protease inhibitor) resistance in HIV-1 in vivo and in vitro. Curr. Pharm. Des. 2004, 10 (32), 4055-64.
4. Fontas, E.; van Leth, F.; Sabin, C. A.; Friis-Moller, N.; Rickenbach, M.; d'Arminio Monforte, A.; Kirk, O.; Dupon, M.; Morfeldt, L.; Mateu, S.; Petoumenos, K.; El-Sadr, W.; de Wit, S.; Lundgren, J. D.; Pradier, C.; Reiss, P. Lipid profiles in HIV-infected patients receiving combination antiretroviral therapy: are different antiretroviral drugs associated with different lipid profiles. J. Infect. Dis. 2004, 189 (6), 1056-74.
5. de Bethune, M. P.; Hertogs, K. Screening and selecting for optimized antiretroviral drugs: rising to the challenge of drug resistance. Curr. Med. Res. Opin. 2006, 22 (12), 2603-12.
6. Machouf, N.; Thomas, R.; Nguyen, V. K.; Trottier, B.; Boulassel, M. R.; Wainberg, M. A.; Routy, J. P. Effects of drug resistance on viral load in patients failing antiretroviral therapy. J. Med. Virol. 2006, 78 (5), 608-13.
7. Potter, S. J.; Lemey, P.; Dyer, W. B.; Sullivan, J. S.; Chew, C. B.; Vandamme, A. M.; Dwyer, D. E.; Saksena, N. K. Genetic analyses reveal structured HIV-1 populations in serially sampled T lymphocytes of patients receiving HAART. Virology 2006, 348 (1), 35-46.
8. Tozzi, V.; Zaccarelli, M.; Bonfigli, S.; Lorenzini, P.; Liuzzi, G.; Trotta, M. P.; Forbici, F.; Gori, C.; Bertoli, A.; Bellagamba, R.; Narciso, P.; Perno, C. F.; Antinori, A. Drug-class-wide resistance to antiretrovirals in HIV-infected patients failing therapy: prevalence, risk factors and virological outcome. Antiviral Ther. 2006, 11 (5), 553-60.
9. Cozzi-Lepri, A.; Phillips, A. N.; Ruiz, L.; Clotet, B.; Loveday, C.; Kjaer, J.; Mens, H.; Clumeck, N.; Viksna, L.; Antunes, F.; Machala, L.; Lundgren, J. D. Evolution of drug resistance in HIV-infected patients remaining on a virologically failing combination antiretroviral therapy regimen. AIDS 2007, 21 (6), 721-32.
10. Friis-Moller, N.; Reiss, P.; Sabin, C. A.; Weber, R.; Monforte, A.; El-Sadr, W.; Thiebaut, R.; De Wit, S.; Kirk, O.; Fontas, E.; Law, M. G.; Phillips, A.; Lundgren, J. D. Class of antiretroviral drugs and the risk of myocardial infarction. N. Engl. J. Med. 2007, 356 (17), 1723-35.
11. Fatkenheuer, G.; Pozniak, A. L.; Johnson, M. A.; Plettenberg, A.; Staszewski, S.; Hoepelman, A. I.; Saag, M. S.; Goebel, F. D.; Rockstroh, J. K.; Dezube, B. J.; Jenkins, T. M.; Medhurst, C.; Sullivan, J. F.; Ridgway, C.; Abel, S.; James, I. T.; Youle, M.; van der Ryst, E. Efficacy of short-term monotherapy with maraviroc, a new CCR5 antagonist, in patients infected with HIV-1. Nat. Med. 2005, 11 (11), 1170-2.
12. Nelson, M.; Fätkenheuer, G.; Konourina, I.; Lazzarin, A.; Clumeck, N.; Horban, A.; Tawadrous, M.; Sullivan, J. H.; Mayer, H.; van der Ryst, E. Efficacy and Safety of Maraviroc Plus Optimized Background Therapy in Viremic, ART-Experienced Patients Infected with CCR5-Tropic HIV-1 in Europe, Australia, and North America: 24-Week Results.; 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, February 25-28, 2007; Los Angeles, CA, 2007.
13. Opar, A. New HIV drug classes on the horizon. Nat. Rev. Drug Discovery 2007, 6 (4), 258-9.
14. Dayam, R.; Al-Mawsawi, L. Q.; Neamati, N. HIV-1 Integrase inhibitors: An emerging clinical reality. Drugs R&D 2007, 8 (3), 155-68.
15. Bushman, F. D.; Craigie, R. Activities of human immunodeficiency virus (HIV) integration protein in vitro: specific cleavage and integration of HIV DNA. Proc. Natl. Acad. Sci. U. S. A. 1991, 88 (4), 1339-43.
16. Brown, P. O. Integration. In Retroviruses; Coffin, J. M., Hughes, S. H., Varmus, H. E., Eds.; Cold Spring Harbor Laboratory Press: Cold Spring Harbor, NY, 1997; pp 161-203.
17. Neamati, N. Patented small molecule inhibitors of HIV-1 integrase: a 10-year saga. Expert Opin. Ther. Pat. 2002, 12 (5), 709-724.
18. Dayam, R.; Neamati, N. Small-molecule HIV-1 integrase inhibitors: the 2001-2002 update. Curr. Pharm. Des. 2003, 9 (22), 1789-802.
19. Dayam, R.; Deng, J.; Neamati, N. HIV-1 integrase inhibitors: 2003-2004 update. Med. Res. Rev. 2006, 26 (3), 271-309.
20. Pommier, Y.; Johnson, A. A.; Marchand, C. Integrase inhibitors to treat HIV/AIDS. Nat Rev Drug Discovery 2005, 4 (3), 236-48.
21. Savarino, A. A historical sketch of the discovery and development of HIV-1 integrase inhibitors. Expert Opin Invest. Drugs 2006, 15 (12), 1507-22.
22. Hazuda, D. J.; Felock, P.; Witmer, M.; Wolfe, A.; Stillmock, K.; Grobler, J. A.; Espeseth, A.; Gabryelski, L.; Schleif, W.; Blau, C.; Miller, M. D. Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells. Science 2000, 287 (5453), 646-50.
23. Billich, A. S-1360 Shionogi-GlaxoSmithKline. Curr. Opin. Invest. Drugs 2003, 4 (2), 206-9.
24. Rosemond, M. J.; St. John-Williams, L.; Yamaguchi, T.; Fujishita, T.; Walsh, J. S. Enzymology of a carbonyl reduction clearance pathway for the HIV integrase inhibitor, S-1360: role of human liver cytosolic aldo-keto reductases. Chem. Biol. Interact. 2004, 147 (2), 129-39.
25. Deng, J.; Dayam, R.; Al-Mawsawi, L. Q.; Neamati, N. Design of second generation HIV-1 integrase inhibitors. Curr. Pharm. Des. 2007, 13 (2), 129-41.
26. Markowitz, M.; Morales-Ramirez, J. O.; Nguyen, B. Y.; Kovacs, C. M.; Steigbigel, R. T.; Cooper, D. A.; Liporace, R.; Schwartz, R.; Isaacs, R.; Gilde, L. R.; Wenning, L.; Zhao, J.; Teppler, H. Antiretroviral activity, pharmacokinetics, and tolerability of MK-0518, a novel inhibitor of HIV-1 integrase, dosed as monotherapy for 10 days in treatment-naive HIV-1-infected individuals. J. Acquired Immune Defic. Syndr. 2006, 43 (5), 509-15.
27. Grinsztejn, B.; Nguyen, B. Y.; Katlama, C.; Gatell, J. M.; Lazzarin, A.; Vittecoq, D.; Gonzalez, C. J.; Chen, J.; Harvey, C. M.; Isaacs, R. D. Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment-experienced patients with multidrug-resistant virus: a phase II randomised controlled trial. Lancet 2007, 369 (9569), 1261-9.
28. Cooper, D.; Gatell, J.; Rockstroh, J.; Katlama, C.; Yeni, P.; Lazzarin, A.; Chen, J.; Isaacs, R.; Teppler, H.; Nguyen, B.; and for the BENCHMRK-Study Group. Results of BENCHMRK-1, a Phase III Study Evaluating the Efficacy and Safety of MK-0518, a Novel HIV-1 Integrase Inhibitor, in Patients with Triple-Class Resistant Virus; 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, USA, February 25-28, 2007; Los Angeles, CA, 2007.
29. Steigbigel, R.; Kumar, P.; Eron, J.; Schechter, M.; Markowitz, M.; Loufty, M.; Zhao, J.; Isaacs, R.; Nguyen, B.; Teppler, H.; and for the BENCHMRK-Study Group. Results of BENCHMRK-2, a Phase III Study Evaluating the Efficacy and Safety of MK-0518, a Novel HIV-1 Integrase Inhibitor, in Patients with Triple-Class Resistant Virus; 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, USA, February 25-28, 2007; Los Angeles, CA, 2007.
30. Sato, M.; Motomura, T.; Aramaki, H.; Matsuda, T.; Yamashita, M.; Ito, Y.; Kawakami, H.; Matsuzaki, Y.; Watanabe, W.; Yamataka, K.; Ikeda, S.; Kodama, E.; Matsuoka, M.; Shinkai, H. Novel HIV-1 integrase inhibitors derived from quinolone antibiotics. J. Med. Chem. 2006, 49 (5), 1506-8.
31. DeJesus, E.; Berger, D.; Markowitz, M.; Cohen, C.; Hawkins, T.; Ruane, P.; Elion, R.; Farthing, C.; Zhong, L.; Cheng, A. K.; McColl, D.; Kearney, B. P. Antiviral activity, pharmacokinetics, and dose response of the HIV-1 integrase inhibitor GS-9137 (JTK-303) in treatment-naive and treatment-experienced patients. J. Acquired Immune Defic. Syndr. 2006, 43 (1), 1-5.
32. Zolopa, A. R.; Mullen, M.; Berger, D.; Ruane, P.; Hawkins, T.; Zhong, L.; Chuck, S.; Enejosa, J.; Kearney, B.; Cheng, A. The HIV Integrase Inhibitor GS-9137 Demonstrates Potent Antiretroviral Activity in Treatment-Experienced Patients; 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, USA., February 25-28, 2007; Los Angeles, CA, 2007.
33. Jones, G.; Ledford, R.; Yu, F.; Miller, M.; Tsiang, M.; McColl, D. Resistance Profile of HIV-1 Mutants in Vitro Selected by the HIV-1 Integrase Inhibitor, GS-9137 (JTK-303); 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, February 25-28, 2007; Los Angeles, CA, 2007.
34. Catalyst; Accelrys, Inc.: San Diego, CA.
35. Smellie, A.; Dyda, F.; Hickman, A. B. Poling-Promoting conformational variation. J. Comput. Chem. 1995, 16, 171-187.
36. Smellie, A.; Kahn, S. D.; Teig, S. L. Analysis of conformational coverage 0.1. Validation and estimation of coverage. J. Chem. Inf. Comput. Sci. 1995, 35 (2), 285-294.
37. Smellie, A.; Kahn, S. D.; Teig, S. L. Analysis of conformational coverage 0.2. Application of conformational models. J. Chem. Inf. Comput. Sci. 1995, 35 (2), 295-304.
38. Goldgur, Y.; Dyda, F.; Hickman, A. B.; Jenkins, T. M.; Craigie, R.; Davies, D. R. Three new structures of the core domain of HIV-1 integrase: an active site that binds magnesium. Proc. Natl. Acad. Sci. U. S. A. 1998, 95 (16), 9150-4.
39. Goldgur, Y.; Craigie, R.; Cohen, G. H.; Fujiwara, T.; Yoshinaga, T.; Fujishita, T.; Sugimoto, H.; Endo, T.; Murai, H.; Davies, D. R. Structure of the HIV-1 integrase catalytic domain complexed with an inhibitor: a platform for antiviral drug design. Proc. Natl. Acad. Sci. U. S. A. 1999, 96 (23), 13040-3.
40. GOLD 3.1; The Cambridge Crystallographic Data Centre: Cambridge, U.K., 2005.
41. 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 (1), 235-42.
42. Nissink, J. W.; Murray, C.; Hartshorn, M.; Verdonk, M. L.; Cole, J. C.; Taylor, R. A new test set for validating predictions of protein-ligand interaction. Proteins 2002, 49 (4), 457-71.
43. Verdonk, M. L.; Cole, J. C.; Hartshorn, M. J.; Murray, C. W.; Taylor, R. D. Improved protein-ligand docking using GOLD. Proteins 2003, 52 (4), 609-23.
44. Verdonk, M. L.; Chessari, G.; Cole, J. C.; Hartshorn, M. J.; Murray, C. W.; Nissink, J. W.; Taylor, R. D.; Taylor, R. Modeling water molecules in protein-ligand docking using GOLD. J. Med. Chem. 2005, 48 (20), 6504-15.
45. Miyoshi, L.; Taguchi, H.; Kobonishi, I.; Yoshimoto, S.; Ohtsuki, Y.; Shiraishi, Y. Type C virus-producing cell lines derived from adult T cell leukemia. Gann Monogr. Cancer Res. 1982, 28, 219-28.
46. Popovic, M.; Sarngadharan, M. G.; Read, E.; Gallo, R. C. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science 1984, 224 (4648), 497-500.
47. Pauwels, R.; Balzarini, J.; Baba, M.; Snoeck, R.; Schols, D.; Herdewijn, P.; Desmyter, J.; De Clercq, E. Rapid and automated tetrazolium-based colorimetric assay for the detection of anti-HIV compounds. J. Virol. Methods 1988, 20 (4), 309-21.
48. Witvrouw, M.; Pannecouque, C.; Switzer, W. M.; Folks, T. M.; De Clercq, E.; Heneine, W. Susceptibility of HIV-2, SIV and SHIV to various anti-HIV-1 compounds: implications for treatment and postexposure prophylaxis. Antiviral Ther. 2004, 9 (1), 57-65.