Fragment-based discovery of bromodomain inhibitors part 2: Optimization of phenylisoxazole sulfonamides

Journal of Medicinal Chemistry

Volumn 55, Issue 2, 2012, Pages 587-596

  Bamborough, Paul ^a   Diallo, Hawa ^a   Goodacre, Jonathan D ^a   Gordon, Laurie ^a   Lewis, Antonia ^a   Seal, Jonathan T ^a   Wilson, David M ^a   Woodrow, Michael D ^a   Chung, Chun Wa ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

4 PHENYL 3,5 DIMETHYL ISOXAZOLE; INTERLEUKIN 6; PHENYLISOXAZOLE SULFONAMIDE; SULFONAMIDE; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ANTIINFLAMMATORY ACTIVITY; ARTICLE; CELL ASSAY; CRYSTAL STRUCTURE; DRUG SOLUBILITY; HUMAN; HUMAN CELL; HYDROGEN BOND; IC 50; PHARMACOPHORE; PHENOTYPE; PROCESS OPTIMIZATION; STRUCTURE ACTIVITY RELATION;

ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; CRYSTALLOGRAPHY, X-RAY; CYTOKINES; FLUORESCENCE POLARIZATION; HUMANS; ISOXAZOLES; LEUKOCYTES, MONONUCLEAR; MODELS, MOLECULAR; MOLECULAR STRUCTURE; NUCLEAR PROTEINS; PROTEIN BINDING; PROTEIN-SERINE-THREONINE KINASES; SOLUBILITY; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONAMIDES; SURFACE PLASMON RESONANCE; TRANSCRIPTION FACTORS;

EID: 84856399470     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm201283q     Document Type: Article

References (24)

1. Sanchez, R.; Zhou, M. M. The role of human bromodomains in chromatin biology and gene transcription Curr. Opin. Drug Discovery Dev. 2009, 12, 659-665
2. Denis, G. V. Bromodomain coactivators in cancer, obesity, type 2 diabetes, and inflammation Discoveries. Med. 2010, 10, 489-499
3. Denis, G. V.; Nikolajczyk, B. S.; Schnitzler, G. R. An emerging role for bromodomain-containing proteins in chromatin regulation and transcriptional control of adipogenesis FEBS Lett. 2010, 584, 3260-3268
4. Florence, B.; Faller, D. V. You bet-cha: a novel family of transcriptional regulators Front. Biosci. 2001, 6, D1008-D1018
5. Nicodeme, E.; Jeffrey, K. L.; Schaefer, U.; Beinke, S.; Dewell, S.; Chung, C. W.; Chandwani, R.; Marazzi, I.; Wilson, P.; Coste, H.; White, J.; Kirilovsky, J.; Rice, C. M.; Lora, J. M.; Prinjha, R. K.; Lee, K.; Tarakhovsky, A. Suppression of inflammation by a synthetic histone mimic Nature 2010, 468, 1119-1123
6. Filippakopoulos, P.; Qi, J.; Picaud, S.; Shen, Y.; Smith, W. B.; Fedorov, O.; Morse, E. M.; Keates, T.; Hickman, T. T.; Felletar, I.; Philpott, M.; Munro, S.; McKeown, M. R.; Wang, Y.; Christie, A. L.; West, N.; Cameron, M. J.; Schwartz, B.; Heightman, T. D.; La, T. N.; French, C. A.; Wiest, O.; Kung, A. L.; Knapp, S.; Bradner, J. E. Selective inhibition of BET bromodomains Nature 2010, 468, 1067-1073
7. Chung, C.; Dean, T.; Woolven, J.; Bamborough, P. Fragment-Based Discovery of Bromodomain Inhibitors Part 1: Inhibitor Binding Modes and Implications for Lead Discovery. J. Med. Chem. 10.1021/jm201320w.
8. Schulz, M. N.; Hubbard, R. E. Recent progress in fragment-based lead discovery Curr. Opin. Pharmacol. 2009, 9, 615-621
9. Hopkins, A. L.; Groom, C. R.; Alex, A. Ligand efficiency: a useful metric for lead selection Drug Discovery Today 2004, 9, 430-431 (Pubitemid 38510559)
10. Chung, C.; Coste, H.; White, J. H.; Mirguet, O.; Wilde, J.; Gosmini, R. L.; Delves, C.; Magny, S. M.; Woodward, R.; Hughes, S. A.; Boursier, E. V.; Flynn, H.; Bouillot, A. M.; Bamborough, P.; Brusq, J. M.; Gellibert, F. J.; Jones, E. J.; Riou, A. M.; Homes, P.; Martin, S. L.; Uings, I. J.; Toum, J.; Clement, C. A.; Boullay, A. B.; Grimley, R. L.; Blandel, F. M.; Prinjha, R. K.; Lee, K.; Kirilovsky, J.; Nicodeme, E. Discovery and Characterization of Small Molecule Inhibitors of the BET Family Bromodomains J. Med. Chem. 2011, 54, 3827-3838
11. The Structural Genomics Consortium. http://www.thesgc.org, 2011.
12. Wells, J. A.; McClendon, C. L. Reaching for high-hanging fruit in drug discovery at protein-protein interfaces Nature 2007, 450, 1001-1009 (Pubitemid 350273630)
13. Dömling, A. Small molecular weight protein-protein interaction antagonists: an insurmountable challenge? Curr. Opin. Chem. Biol. 2008, 12, 281-291
14. Meireles, L. M.; Mustata, G. Discovery of modulators of protein-protein interactions: current approaches and limitations Curr. Top. Med. Chem. 2011, 11, 248-257
15. Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J. Experimental and computational approaches to estimate solubiltiy and permeability in drug discovery and development settings Adv. Drug Delivery Rev. 1997, 23, 3-25 (Pubitemid 27046991)
16. Morelli, X.; Bourgeas, R.; Roche, P. Chemical and structural lessons from recent successes in protein-protein interaction inhibition (2P2I) Curr. Opin. Chem. Biol. 2011, 15, 475-481
17. Bouillot, A.-M.; Donche, F.; Gellibert, F.; Lamotte, Y.; Mirguet, O. Imidazo[4,5- c ]quinoline derivatives as bromodomain inhibitors and their preparation and use in the treatment of cancer, chronic autoimmune and inflammatory disease. WO2011054846, 2011.
18. Dawson, M. A.; Prinjha, R. K.; Dittmann, A.; Giotopoulos, G.; Bantscheff, M.; Chan, W. I.; Robson, S. C.; Chung, C. W.; Hopf, C.; Savitski, M. M.; Huthmacher, C.; Gudgin, E.; Lugo, D.; Beinke, S.; Chapman, T. D.; Roberts, E. J.; Soden, P. E.; Auger, K. R.; Mirguet, O.; Doehner, K.; Delwel, R.; Burnett, A. K.; Jeffrey, P.; Drewes, G.; Lee, K.; Huntly, B. J.; Kouzarides, T. Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia Nature 2011, 478, 529-533
19. Mirguet, O.; Lamotte, Y.; Donche, F.; Toum, J.; Gellibert, F.; Bouillot, A.; Gosmini, R.; Nguyen, V. L.; Delannée, D.; Seal, J.; Blandel, F.; Boullay, A. B.; Boursier, E.; Martin, S.; Brusq, J. M.; Krysa, G.; Riou, A.; Tellier, R.; Costaz, A.; Huet, P.; Dudit, Y.; Trottet, L.; Nicodeme, E. From ApoA1 upregulation to BET family Bromodomain inhibition: Discovery of I-BET151 (GSK1210151A). Submitted for publication.
20. Lamotte, Y.; Donche, F.; Bouillot, A.; Mirguet, O.; Gellibert, F.; Nicodeme, E.; Krysa, G.; Beinke, S.; McCleary, S.; Rioja, I.; Bamborough, P.; Chung, C.; Gordon, L.; Lewis, A.; Walker, A.; Cutler, L.; Lugo, J.; Seal, J. Identification of a novel series of BET family Bromodomain inhibitors: binding mode and profile of IBET-151 (GSK1210151A). Submitted for publication.
21. Hewings, D. S.; Wang, M.; Philpott, M.; Fedorov, O.; Uttarkar, S.; Filippakopoulos, P.; Picaud, S.; Vuppusetty, C.; Marsden, B.; Knapp, S.; Conway, S.; Heightman, T. D. 3,5-Dimethylisoxazoles act as acetyl-lysine-mimetic bromodomain ligands J. Med. Chem. 2011, 54, 6761-6770
22. Molecular Operating Environment (MOE), version 2008.10; Chemical Computing Group (CCG), 2011.
23. Jaguar, version 7.8; Schrodinger, LLC, New York, 2011.
24. Moriniere, J.; Rousseaux, S.; Steuerwald, U.; Soler-Lopez, M.; Curtet, S.; Vitte, A. L.; Govin, J.; Gaucher, J.; Sadoul, K.; Hart, D. J.; Krijgsveld, J.; Khochbin, S.; Muller, C. W.; Petosa, C. Cooperative binding of two acetylation marks on a histone tail by a single bromodomain Nature 2009, 461, 664-668