De novo fragment design: A medicinal chemistry approach to fragment-based lead generation

Journal of Medicinal Chemistry

Volumn 56, Issue 7, 2013, Pages 3115-3119

  Talamas, Francisco X ^a   Ao Ieong, Gloria ^a   Brameld, Ken A ^a   Chin, Elbert ^a   De Vicente, Javier ^a   Dunn, James P ^a   Ghate, Manjiri ^a   Giannetti, Anthony M ^a   Harris, Seth F ^a   Labadie, Sharada S ^a   Leveque, Vincent ^a   Li, Jim ^a   Lui, Alfred S T ^a   McCaleb, Kristen L ^a   Nájera, Isabel ^a   Schoenfeld, Ryan C ^a   Wang, Beihan ^a   Wong, April ^a  

^a HOFFMANN LA ROCHE INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; BINDING AFFINITY; CHEMICAL MODEL; FRAGMENTATION REACTION; MOLECULAR LIBRARY;

CHEMISTRY, PHARMACEUTICAL; DRUG DESIGN; MODELS, MOLECULAR;

EID: 84876240636     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm4002605     Document Type: Article

References (19)

1. Wendt, M. D. Discovery of ABT-263, a Bcl-Family Protein Inhibitor: Observations on Targeting a Large Protein-Protein Interaction Expert Opin. Drug Discovery 2008, 3, 1123-1143
2. Wyatt, P. G.; Woodhead, A. J.; Berdini, V.; Boulstridge, J. A.; Carr, M. G.; Cross, D. M.; Davis, D. J.; Devine, L. A.; Early, T. R.; Feltell, R. E.; Lewis, E. J.; McMenamin, R. L.; Navarro, E. F.; O'Brien, M. A.; O'Reilly, M.; Reule, M.; Saxty, G.; Seavers, L. C. A.; Smith, D. M.; Squires, M. S.; Trewartha, G.; Walker, M. T.; Woolford, A. J. A. Identification of N -(4-Piperidinyl)-4-(2,6-dichlorobenzoylamino)-1 H -pyrazole-3-carboxamide (AT7519), A Novel Cyclin Dependent Kinase Inhibitor Using Fragment-Based X-Ray Crystallography and Structure Based Drug Design J. Med. Chem. 2008, 51, 4986-4999
3. Bollag, G.; Tsai, J.; Zhang, J.; Zhang, Ch.; Ibrahim, P.; Nolop, K.; Hirth, P. Vemurafenib: The First Drug Approved for BRAF-Mutant Cancer Nature Rev. Drug Discovery 2012, 11, 873-886
4. Erlanson, D. A. Introduction to Fragment-Based Drug Discovery Top. Curr. Chem. 2012, 317, 1-32
5. Nishibata, Y.; Itai, A. Automatic Creation of Drug Candidate Structures Based on Receptor Structure. Starting Point for Artificial Lead Generation Tetrahedron 1991, 47, 8985-8990
6. Loving, K.; Alberts, I.; Sherman, W. Computational Approaches for Fragment-Based and de Novo Design Curr. Top. Med. Chem. 2010, 10, 14-32
7. Rognan, D. Fragment-Based Approaches and Computer-Aided Drug Discovery Top. Curr. Chem. 2012, 317, 201-222
8. Sofia, M. J.; Chang, W.; Furman, P. A.; Mosley, R. T.; Ross, B. S. Nucleoside, Nucleotide, and Non-Nucleoside Inhibitors of Hepatitis C Virus NS5B RNA-Dependent RNA-Polymerase J. Med. Chem. 2012, 55, 2481-2531
9. Le Pogam, S.; Seshaadri, A.; Kosaka, A.; Chiu, S.; Kang, H.-S.; Hu, S.; Rajyaguru, S.; Symons, J.; Cammack, N.; Najera, I. Existence of Hepatitis C Virus NS5B Variants Naturally Resistant to Non-Nucleoside, but not to Nucleoside, Polymerase Inhibitors Among Untreated Patients J. Antimicrob. Chemother. 2008, 61, 1205-1216
10. de Vicente, J.; Hendricks, R. T.; Smith, D. B.; Fell, J. B.; Fischer, J.; Spencer, S. R.; Stengel, P. J.; Mohr, P.; Robinson, J. E.; Blake, J. F.; Hilgenkamp, R. K.; Yee, C.; Adjabeng, G.; Elworthy, T. R.; Tracy, J.; Chin, E.; Li, J.; Wang, B.; Bamberg, J. T.; Stephenson, R.; Oshiro, C.; Harris, S. F.; Ghate, M.; Leveque, V.; Najera, I.; Le Pogam, S.; Rajyaguru, S.; Ao-Ieong, G.; Alexandrova, L.; Larrabee, S.; Brandl, M.; Briggs, A.; Sukhtankar, S.; Farrell, R.; Xu, B. Non-Nucleoside Inhibitors of HCV Polymerase NS5B. Part 2: Synthesis and Structure-Activity Relationships of Benzothiazine-Substituted Quinolinediones Bioorg. Med. Chem. Lett. 2009, 19, 3642-3646
11. de Vicente, J.; Hendricks, R. T.; Smith, D. B.; Fell, J. B.; Fischer, J.; Spencer, S. R.; Stengel, P. J.; Mohr, P.; Robinson, J. E.; Blake, J. F.; Hilgenkamp, R. K.; Yee, C.; Zhao, J.; Elworthy, T. R.; Tracy, J.; Chin, E.; Li, J.; Lui, A.; Wang, B.; Oshiro, C.; Harris, S. F.; Ghate, M.; Leveque, V. J. P.; Najera, I.; Le Pogam, S.; Rajyaguru, S.; Ao-Ieong, G.; Alexandrova, L.; Fitch, B.; Brandl, M.; Masjedizadeh, M.; Wu, S.; de Keczer, S.; Voronin, T. Non-Nucleoside Inhibitors of HCV Polymerase NS5B. Part 3: Synthesis and Optimization Studies of Benzothiazine-Substituted Tetramic Acids Bioorg. Med. Chem. Lett. 2009, 19, 5648-5651
12. Pfefferkorn, J. A.; Greene, M. L.; Nugent, R. A.; Gross, R. J.; Mitchell, M. A.; Finzel, B. C.; Harris, M. S.; Wells, P. A.; Shelly, J. A.; Anstadt, R. A.; Kilkuskie, R. E.; Koptab, L. A.; Schwendea, F. J. Inhibitors of HCV NS5B Polymerase. Part 1: Evaluation of the Southern Region of (2 Z)-2-(Benzoylamino)- 3-(5-phenyl-2-furyl)acrylic Acid Bioorg. Med. Chem. Lett. 2005, 15, 2481-2486
13. Gopalsamy, A.; Chopra, R.; Lim, K.; Ciszewski, G.; Shi, M.; Curran, K. J.; Sukits, S. F.; Svenson, K.; Bard, J.; Ellingboe, J. W.; Agarwal, A.; Krishnamurthy, G.; Howe, A. Y. M.; Orlowski, M.; Feld, B.; O′Connell, J.; Mansour, T. S. Discovery of Proline Sulfonamides as Potent and Selective Hepatitis C Virus NS5b Polymerase Inhibitors. Evidence for a New NS5b Polymerase Binding Site J. Med. Chem. 2006, 49, 3052-3055
14. Slater, M. J.; Amphlett, E. M.; Andrews, D. M.; Bravi, G.; Burton, G.; Cheasty, A. G.; Corfield, J. A.; Ellis, M. R.; Fenwick, R. H.; Fernandes, S.; Guidetti, R.; Haigh, D.; Hartley, C. D.; Howes, P. D.; Jackson, D. L.; Jarvest, R. L.; Lovegrove, V. L. H.; Medhurst, K. J.; Parry, N. P.; Price, H.; Shah, P.; Singh, O. M. P.; Stocker, R.; Thommes, P.; Wilkinson, C.; Wonacott, A. Optimization of Novel Acyl Pyrrolidine Inhibitors of Hepatitis C Virus RNA-Dependent RNA Polymerase Leading to a Development Candidate J. Med. Chem. 2007, 50, 897-900
15. Brameld, K. A.; Kuhn, B.; Reuter, D. C.; Stahl, M. Small Molecule Conformational Preferences Derived from Crystal Structure Data. A Medicinal Chemistry Focused Analysis J. Chem. Inf. Model. 2008, 48, 1-24
16. Molecular Operating Environment (MOE); Chemical Computing Group Inc.: 1010 Sherbooke Street West, Suite #910, Montreal, QC, Canada, H3A 2R7, 2008.
17. Hopkins, A. L.; Groom, C. R.; Alex, A. Ligand Efficiency: A Useful Metric for Lead Selection Drug Discovery Today 2004, 9, 430-431
18. Hajduk, P. J. Fragment-Based Drug Design: How Big is Too Big? J. Med. Chem. 2006, 49, 6972-6976
19. The PyMOL Molecular Graphics System, version 1.5.0.4; Schrödinger, LLC.