From docking false-positive to active anti-HIV agent

Journal of Medicinal Chemistry

Volumn 50, Issue 22, 2007, Pages 5324-5329

  Barreiro, Gabriela ^a   Kim, Joseph T ^a   Guimarães, Cristiano R W ^a   Bailey, Christopher M ^b   Domaoal, Robert A ^b   Wang, Ligong ^b   Anderson, Karen S ^b   Jorgensen, William L ^a  

^a YALE UNIVERSITY   (United States)

^b YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; DIHYDROBENZOFURAN DERIVATIVE; EFAVIRENZ; ETRAVIRINE; N [4 CHLORO 3 (3 METHYL 2 BUTENYLOXY)PHENYL] 2 METHYL 3 FURANCARBOTHIOAMIDE; NEVIRAPINE; OXADIAZOLE DERIVATIVE; RNA DIRECTED DNA POLYMERASE INHIBITOR; S 10087; SDABO 3 W; SDABO 3W; STAVUDINE; UNCLASSIFIED DRUG;

ANTIVIRAL ACTIVITY; ARTICLE; CHEMICAL MODIFICATION; DRUG SYNTHESIS; FALSE POSITIVE RESULT; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MATHEMATICAL COMPUTING; MOLECULAR DOCKING; MOLECULAR MECHANICS; NONHUMAN; SCORING SYSTEM; SCREENING TEST; SURFACE PROPERTY; VIRTUAL REALITY MODELING LANGUAGE;

ANTI-HIV AGENTS; CELL LINE; DATABASES, FACTUAL; HIV REVERSE TRANSCRIPTASE; HIV-1; HUMANS; LIGANDS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; OXADIAZOLES; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; REVERSE TRANSCRIPTASE INHIBITORS; THERMODYNAMICS;

EID: 35848968698     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm070683u     Document Type: Article

References (39)

1. AIDS Epidemie Update: December 2006; UNAIDS/WHO: Geneva, Switzerland, 2006.
2. (a) Kohlstaedt, L. A.; Wang, J.; Friedman, J. M.; Rice, P. A.; Steitz, T. A. Crystal structure at 3.5 Å resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science 1992, 256, 1783-1790.
3. (b) Smerdon, S. J.; Jäger, J.; Wang, J.; Kohlstaedt, L. A.; Chirino, A. J.; Friedman, J. M.; Rice, P. A.; Steitz, T. A. Structure of the binding site for nonnucleoside inhibitors of reverse transcriptase of human immunodeficiency virus type 1. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 3911-3915.
4. (c) De Clercq, E. New approaches toward anti-HIV chemotherapy. J. Med. Chem. 2005, 48, 1297-313.
5. (a) Jorgensen, W. L.; Ruiz-Caro, J.; Tirado-Rives, J.; Basavapathruni, A.; Anderson, K. S.; Hamilton, A. D. Computer-aided design of non-nucleoside inhibitors of HIV-1 reverse transcriptase. Bioorg. Med. Chem. Lett. 2006, 16, 663-667.
6. (b) Ruiz-Caro, J.; Basavapathruni, A.; Kim, J. T.; Wang, L.; Bailey, C. M.; Anderson, K. S.; Hamilton, A. D.; Jorgensen, W. L. Optimization of diarylamines as non-nucleoside inhibitors of HIV-1 reverse transcriptase. Bioorg. Med. Chem. Lett. 2006, 16, 668-671.
7. (c) Thakur, V. V.; Kim, J. T.; Hamilton, A. D.; Bailey, C. M.; Domaoal, R. A.; Wang, L.; Anderson, K. S.; Jorgensen, W. L. Optimization of pyrimidinyl- and triazinylamines as non-nucleoside inhibitors of HIV-1 reverse transcriptase. Bioorg. Med. Chem. Lett. 2006, 16, 5664-5667.
8. (d) Kim, J. T.; Hamilton, A. D.; Bailey, C. M.; Domaoal, R. A.; Wang, L.; Anderson, K. S.; Jorgensen, W. L. FEP-guided selection of bicyclic heterocycles in lead optimization for non-nucleoside inhibitors of HIV-1 reverse transcriptase. J. Am. Chem. Soc. 2006, 128, 15372-15373.
9. (a) Blake, J. F.; Laird, E. R. Recent advances in virtual ligand screening. Annu. Rep. Med. Chem. 2003, 38, 305-314.
10. (b) Leach, A. R.; Shoichet, B. K.; Peishoff, C. E. Prediction of protein-ligand interactions. Docking and scoring: successes and gaps. J. Med. Chem. 2006, 49, 5851-5855.
11. Barreiro, G.; Guimarães, C. R. W.; Tubert-Brohman, I.; Lyons, T. M.; Tirado-Rives, J.; Jorgensen, W. L. Search for non-nucleoside inhibitors of HIV-1 reverse transcriptase using chemical similarity, molecular docking, and MM-GB/SA scoring. J. Chem. Inf. Model., in press.
12. Ren, J.; Esnouf, R. M.; Hopkins, A. L.; Warren, J.; Balzarini, J.; Stuart, D. I.; Stammers, D. K. Crystal structures of HIV-1 reverse transcriptase in complex with carboxanilide derivatives. Biochemistry 1998, 37, 14394-14403.
13. Friesner, R. A.; Banks, J. L.; Murphy, R. B.; Halgren, T. A.; Klicic, J. J.; Mainz, D. T.; Repasky, M. P.; Knoll, E. H.; Shelley, M.; Perry, J. K.; Shaw, D. E.; Francis, P.; Shenkin, P. S. Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J. Med. Chem. 2004, 47, 1739-1749.
14. (a) Jorgensen, W. L.; Maxwell, D. S.; Tirado-Rives, J. Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. J. Am. Chem. Soc. 1996, 118, 11225-11236.
15. (b) Jorgensen, W. L.; Tirado-Rives, J. Chemical theory and computation special feature: Potential energy functions for atomic-level simulations of water and organic and biomolecular systems. Proc. Natl. Acad. Sci U.S.A. 2005, 102, 6665-6670.
16. (a) Still, W. C.; Tempczyk, A.; Hawley, R. C.; Hendrickson, T. Semianalytical treatment of solvation for molecular mechanics and dynamics. J. Am. Chem. Soc. 1990, 112, 6127-6129.
17. (b) Jorgensen, W. L.; Ulmschneider, J. P.; Tirado-Rives, J. Free energies of hydration from a generalized Born model and an all-atom force field. J. Phys. Chem. B 2004, 108, 16264-16270.
18. MacroModel, version 9.0; Schrödinger LLC: New York, 2005.
19. (a) Lin, T. S.; Luo, M. Z.; Liu, M. C.; Pai, S. B.; Dutschman, G. E.; Cheng, Y. C. Antiviral activity of 2′,3′-dideoxy-β-L- 5-fluorocytidine (β-L-EddC) and 2′,3′-dideoxy-β- L-cytidine (β-L-ddC) against hepatitis B virus and human immunodeficiency virus type 1 in vitro. Biochem. Pharmacol. 1994, 47, 171-174.
20. (b) Ray, A. S.; Yang, Z.; Chu, C. K.; Anderson, K. S. Novel use of a guanosine prodrug approach to convert 2′,3′-didehydro-2′, 3′-dideoxyguanosine into a viable antiviral agent. Antimicrob. Agents Chemother. 2002, 46, 887-891.
21. (a) Muraglia, E.; Kinzel, O. D.; Laufer, R.; Miller, M. D.; Moyer, G.; Munshi, V.; Orvieto, F.; Palumbi, M. C.; Pescatore, G.; Rowley, M.; Williams, P. D.; Summa, V. Tetrazole thioacetanilides: Potent non-nucleoside inhibitors of WT HIV reverse transcriptase and its K103N mutant. Bioorg. Med. Chem. Lett. 2006, 16, 2748-2752.
22. (b) Wang, Z.; Wu, B.; Kuhen, K. L.; Bursulaya, B.; Nguyen, T. N.; Nguyen, D. G.; He, Y. Synthesis and biological evaluations of sulfanyltriazoles as novel HIV-1 non-nucleoside reverse transcriptase inhibitors. Bioorg. Med. Chem. Lett. 2006, 16, 4174-4177.
23. (c) De La Rosa, M.; Kim, H. W.; Gunic, E.; Jenket, C.; Boyle, U.; Koh, Y.-H.; Korboukh, I.; Allan, M.; Zhang, W.; Chen, H.; Xu, W.; Nilar, S.; Yao, N.; Hamatake, R.; Lang, S. A.; Hong, Z.; Zhang, Z.; Girardet, J.-L. Tri-substituted triazoles as potent non-nucleoside inhibitors of the HIV-1 reverse transcriptase. Bioorg. Med. Chem. Lett. 2006, 16, 4444-4449.
24. Tirado-Rives, J.; Jorgensen, W. L. Contribution of conformer focusing to the uncertainty in predicting free energies for protein-ligand binding. J. Med. Chem. 2006, 49, 5880-5884.
25. Hann, M. M.; Leach, A. R.; Harper, G. Molecular complexity and its impact on the probability of finding leads for drug discovery. J. Chem. Inf. Comput. Sci. 2001, 41, 856-864.
26. Rizzo, R. C.; Udier-Blagovic, M.; Wang, D. P.; Watkins, E. K.; Kroeger, Smith, M. B.; Smith, R. H., Jr.; Tirado-Rives, J.; Jorgensen, W. L. Prediction of activity for non-nucleoside inhibitors with HIV-1 reverse transcriptase based on Monte Carlo simulations. J. Med. Chem. 2002, 45, 2970-2987.
27. Blagovic, M. U.; Tirado-Rives, J.; Jorgensen, W. L. Validation of a model for the complex of HIV-1 reverse transcriptase with non-nucleoside inhibitor TMC125. J. Am. Chem. Soc. 2003, 125, 6016-6017.
28. Das, K.; Clark, A. D., Jr.; Lewi, P. J.; Heeres, J.; de Jonge, M. R.; Koymans, L. M. H.; Vinkers, H. M.; Daeyaert, F.; Ludovici, D. W.; Kukla, M. J.; De Corte, B.; Kavash, R. W.; Ho, C. Y.; Ye, H.; Lichtenstein, M. A.; Andries, K.; Pauwels, R.; de Béthune, M.-P.; Boyer, P. L.; Clark, P.; Hughes, S. H.; Janssen, P. A. J.; Arnold, E. Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (Etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants. J. Med. Chem. 2004, 47, 2550-2560.
29. Pyrimidines such as 2-6 are in the class Het-NH-Ph-U in which the U group is now delivered into the aryl box formed by Tyr181, Tyr188, Trp229, and Phe227 from the "right" instead of from the "left" as in Figure 1 for 1.
30. Ludovici, D. W.; De Corte, B. L.; Kukla, M. J.; Ye, H.; Ho, C. Y.; Lichtenstein, M. A.; Kavash, R. W.; Andries, K.; de Béthune, M.-P.; Azijn, H.; Pauwels, R.; Lewi, P. J.; Heeres, J.; Koymans, L. M. H.; de Jonge, M. R.; Van Aken, K. J. A.; Daeyaert, F. F. D.; Das, K.; Arnold, E.; Janssen, P. A. J. Evolution of anti-HIV drug candidates. Part 3: Diarylpyrimidine (DAPY) analogues. Bioorg. Med. Chem. Lett. 2001, 11, 2235-2239.
31. Heeres, J.; de Jonge, M. R.; Koymans, L. M. H.; Daeyaert, F. F. D.; Vinkers, M.; Van Aken Koen, J. A.; Arnold, E.; Das, K.; Kilonda, A.; Hoornaert, G. J.; Compernolle, F.; Cegla, M.; Azzam, R. A.; Andries, K.; de Bethune, M.-P.; Azijn, H.; Pauwels, R.; Lewi, P. J.; Janssen, P. A. J. Design, synthesis, and SAR of a novel pyrazinone series with non-nucleoside HIV-1 reverse transcriptase inhibitory activity. J. Med. Chem. 2005, 48, 1910-1918.
32. QikProp, version 3.0; Schrödinger LLC: New York, 2006. QikProp was used as a subroutine with BOMB for each generated structure.
33. Himmel, D. M.; Das, K.; Clark, A. D., Jr.; Hughes, S. H.; Benjahad, A.; Oumouch, S.; Guillemont, J.; Coupa, S.; Poncelet, A.; Csoka, I.; Meyer, C.; Andries, K.; Nguyen, C. H.; Grierson, D. S.; Arnold, E. Crystal structures for HIV-1 reverse transcriptase in complexes with three pyridinone derivatives: A new class of non-nucleoside inhibitors effective against a broad range of drug-resistant strains. J. Med. Chem. 2005, 48, 7582-7591.
34. Tsuzuki, S.; Houjou, H.; Nagawa, Y.; Hiratani, K. The second stable conformation of the methoxy groups of o-dimethoxybenzene: Stabilization of perpendicular conformation by CH-O interaction. J. Chem. Soc., Perkin Trans. 2 2002, 1271-1273.
35. Jorgensen, W. L.; Tirado-Rives, J. Molecular modeling of organic and biomolecular systems using BOSS and MCPRO. J. Comput. Chem. 2005, 26, 1689-1700.
36. 2A receptor antagonists. Bioorg. Med. Chem. Lett. 2004, 14, 817-821.
37. 2- adrenergic receptor. J. Med. Chem. 1987, 30, 1241-1244.
38. Zinner, G.; Heitmann, M. Arbimide and carbonyl cyclizations of semicarbazides. Arch. Pharm. 1981, 314, 193-196.
39. Barreca, M. L.; De Luca, L.; Iraci, N.; Rao, A.; Ferro, S.; Maga, G.; Chimirri, A. Structure-based pharmacophore identification of new chemical scaffolds as non-nucleoside reverse transcriptase inhibitors. J. Chem. Inf. Model. 2007, 47, 557-562.