Fragment-based and structure-guided discovery and optimization of Rho kinase inhibitors

Journal of Medicinal Chemistry

Volumn 55, Issue 5, 2012, Pages 2474-2478

  Li, Rongshi ^a   Martin, Mathew P ^a   Liu, Yan ^a   Wang, Binglin ^a   Patel, Ronil A ^a   Zhu, Jin Yi ^a   Sun, Nan ^a   Pireddu, Roberta ^a   Lawrence, Nicholas J ^a   Li, Jiannong ^a   Haura, Eric B ^a   Sung, Shen Shu ^b   Guida, Wayne C ^a   Schonbrunn, Ernst ^a   Sebti, Said M ^a  

^a H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

^b PENN STATE COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 CHLOROSUBSITUTED NICOTINAMIDE; 4 PARA FLUROPHENYL NICOTINAMIDE; 5 AMINOINDAZOLE; 5 BROMOSUBSITUTED NICOTINAMIDE; 5 PARA FLUROPHENYL NICOTINAMIDE; ADENOSINE TRIPHOSPHATE; ISONICOTINAMIDE; NICOTINAMIDE; PICOLINAMIDE; RHO KINASE INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; BINDING SITE; BREAST CANCER; CANCER CELL; CHEMICAL ANALYSIS; DRUG DESIGN; DRUG STRUCTURE; ENZYME PHOSPHORYLATION; ENZYME SUBSTRATE; HINGE REGION; HUMAN; HUMAN CELL;

ADENOSINE TRIPHOSPHATE; BINDING SITES; CARDIAC MYOSINS; CELL LINE, TUMOR; CRYSTALLOGRAPHY, X-RAY; HUMANS; MITOGEN-ACTIVATED PROTEIN KINASE 1; MITOGEN-ACTIVATED PROTEIN KINASE 3; MODELS, MOLECULAR; MOLECULAR STRUCTURE; MYOSIN LIGHT CHAINS; PHOSPHORYLATION; RHO-ASSOCIATED KINASES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84863237488     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm201289r     Document Type: Article

References (26)

1. Hajduk, P. J.; Greer, J. A decade of fragment-based drug design: strategic advances and lessons learned Nat. Rev. Drug Discovery 2007, 6, 211-219
2. Bohacek, R. S.; McMartin, C.; Guida, W. C. The art and practice of structure-based drug design: a molecular modeling perspective Med. Res. Rev. 1996, 16, 3-50
3. Fink, T.; Reymond, J. L. Virtual exploration of the chemical universe up to 11 atoms of C, N, O, F: assembly of 26.4 million structures (110.9 million stereoisomers) and analysis for new ring systems, stereochemistry, physicochemical properties, compound classes, and drug discovery J. Chem. Inf. Model. 2007, 47, 342-353
4. Jhoti, H.; Cleasby, A.; Verdonk, M.; Williams, G. Fragment-based screening using X-ray crystallography and NMR spectroscopy Curr. Opin. Chem. Biol. 2007, 11, 485-493
5. Navratilova, I.; Hopkins, A. L. Fragment Screening by Surface Plasmon Resonance ACS Med. Chem. Lett. 2010, 1, 44-48
6. Ladbury, J. E.; Klebe, G.; Freire, E. Adding calorimetric data to decision making in lead discovery: a hot tip Nat. Rev. Drug Discovery 2010, 9, 23-27
7. Siegal, G.; Hollander, J. G. Target immobilization and NMR screening of fragments in early drug discovery Curr. Top. Med. Chem. 2009, 9, 1736-1745
8. Hannah, V. V.; Atmanene, C.; Zeyer, D.; Dorsselaer, A. V.; Sanglier-Cianférani, S. Native MS: An 'ESI, way to support structure- and fragment-based drug discovery Future Med. Chem. 2010, 2, 35-50
9. Duong-Thi, M. D.; Meiby, E.; Bergstrom, M.; Fex, T.; Isaksson, R.; Ohlson, S. Weak affinity chromatography as a new approach for fragment screening in drug discovery Anal. Biochem. 2011, 414, 138-146
10. Medina, J. R.; Blackledge, C. W.; Heerding, D. A.; Campobasso, N.; Ward, P.; Briand, J.; Wright, L.; Axten, J. M. Aminoindazole PDK1 Inhibitors: A Case Study in Fragment-Based Drug Discovery ACS Med. Chem. Lett. 2010, 1, 439-442
11. Godemann, R.; Madden, J.; Kramer, J.; Smith, M.; Fritz, U.; Hesterkamp, T.; Barker, J.; Hoppner, S.; Hallett, D.; Cesura, A.; Ebneth, A.; Kemp, J. Fragment-based discovery of BACE1 inhibitors using functional assays Biochemistry 2009, 48, 10743-10751
12. Matthews, T. P.; Klair, S.; Burns, S.; Boxall, K.; Cherry, M.; Fisher, M.; Westwood, I. M.; Walton, M. I.; McHardy, T.; Cheung, K. M.; Van Montfort, R.; Williams, D.; Aherne, G. W.; Garrett, M. D.; Reader, J.; Collins, I. Identification of inhibitors of checkpoint kinase 1 through template screening J. Med. Chem. 2009, 52, 4810-4819
13. Barker, J. J.; Barker, O.; Boggio, R.; Chauhan, V.; Cheng, R. K.; Corden, V.; Courtney, S. M.; Edwards, N.; Falque, V. M.; Fusar, F.; Gardiner, M.; Hamelin, E. M.; Hesterkamp, T.; Ichihara, O.; Jones, R. S.; Mather, O.; Mercurio, C.; Minucci, S.; Montalbetti, C. A.; Muller, A.; Patel, D.; Phillips, B. G.; Varasi, M.; Whittaker, M.; Winkler, D.; Yarnold, C. J. Fragment-based identification of Hsp90 inhibitors ChemMedChem 2009, 4, 963-966
14. Dong, M.; Yan, B. P.; Liao, J. K.; Lam, Y. Y.; Yip, G. W.; Yu, C. M. Rho-kinase inhibition: A novel therapeutic target for the treatment of cardiovascular diseases Drug Discovery Today 2010, 15, 622-629
15. LoGrasso, P. V.; Feng, Y. Rho kinase (ROCK) inhibitors and their application to inflammatory disorders Curr. Top. Med. Chem. 2009, 9, 704-723
16. Micuda, S.; Rosel, D.; Ryska, A.; Brabek, J. ROCK inhibitors as emerging therapeutic candidates for sarcomas Curr. Cancer Drug Targets 2010, 10, 127-134
17. Yang, X.; Zhang, Y.; Wang, S.; Shi, W. Effect of fasudil on growth, adhesion, invasion, and migration of 95D lung carcinoma cells in vitro Can. J. Physiol. Pharmacol. 2010, 88, 874-879
18. Kidera, Y.; Tsubaki, M.; Yamazoe, Y.; Shoji, K.; Nakamura, H.; Ogaki, M.; Satou, T.; Itoh, T.; Isozaki, M.; Kaneko, J.; Tanimori, Y.; Yanae, M.; Nishida, S. Reduction of lung metastasis, cell invasion, and adhesion in mouse melanoma by statin-induced blockade of the Rho/Rho-associated coiled-coil-containing protein kinase pathway J. Exp. Clin. Cancer Res. 2010, 29, 127
19. Hajduk, P. J. Fragment-based drug design: How big is too big? J. Med. Chem. 2006, 49, 6972-6976
20. Iwakubo, M.; Takami, A.; Okada, Y.; Kawata, T.; Tagami, Y.; Ohashi, H.; Sato, M.; Sugiyama, T.; Fukushima, K.; Iijima, H. Design and synthesis of Rho kinase inhibitors (II) Bioorg. Med. Chem. 2007, 15, 350-364
21. Takami, A.; Iwakubo, M.; Okada, Y.; Kawata, T.; Odai, H.; Takahashi, N.; Shindo, K.; Kimura, K.; Tagami, Y.; Miyake, M.; Fukushima, K.; Inagaki, M.; Amano, M.; Kaibuchi, K.; Iijima, H. Design and synthesis of Rho kinase inhibitors (I) Bioorg. Med. Chem. 2004, 12, 2115-2137
22. Jacobs, M.; Hayakawa, K.; Swenson, L.; Bellon, S.; Fleming, M.; Taslimi, P.; Doran, J. The structure of dimeric ROCK I reveals the mechanism for ligand selectivity J. Biol. Chem. 2006, 281, 260-268
23. Sehon, C. A.; Wang, G. Z.; Viet, A. Q.; Goodman, K. B.; Dowdell, S. E.; Elkins, P. A.; Semus, S. F.; Evans, C.; Jolivette, L. J.; Kirkpatrick, R. B.; Dul, E.; Khandekar, S. S.; Yi, T.; Wright, L. L.; Smith, G. K.; Behm, D. J.; Bentley, R.; Doe, C. P.; Hu, E.; Lee, D. Potent, selective and orally bioavailable dihydropyrimidine inhibitors of Rho kinase (ROCK1) as potential therapeutic agents for cardiovascular diseases J. Med. Chem. 2008, 51, 6631-6634
24. Yoshimi, E.; Kumakura, F.; Hatori, C.; Hamachi, E.; Iwashita, A.; Ishii, N.; Terasawa, T.; Shimizu, Y.; Takeshita, N. Antinociceptive effects of AS1892802, a novel Rho kinase inhibitor, in rat models of inflammatory and noninflammatory arthritis J. Pharmacol. Exp. Ther. 2010, 334, 955-963
25. Ray, P.; Wright, J.; Adam, J.; Bennett, J.; Boucharens, S.; Black, D.; Cook, A.; Brown, A. R.; Epemolu, O.; Fletcher, D.; Haunso, A.; Huggett, M.; Jones, P.; Laats, S.; Lyons, A.; Mestres, J.; de Man, J.; Morphy, R.; Rankovic, Z.; Sherborne, B.; Sherry, L.; van Straten, N.; Westwood, P.; Zaman, G. Z. Fragment-based discovery of 6-substituted isoquinolin-1-amine based ROCK-I inhibitors Bioorg. Med. Chem. Lett. 2011, 21, 97-101
26. Ray, P.; Wright, J.; Adam, J.; Boucharens, S.; Black, D.; Brown, A. R.; Epemolu, O.; Fletcher, D.; Huggett, M.; Jones, P.; Laats, S.; Lyons, A.; de Man, J.; Morphy, R.; Sherborne, B.; Sherry, L.; Straten, N.; Westwood, P.; York, M. Optimisation of 6-substituted isoquinolin-1-amine based ROCK-I inhibitors Bioorg. Med. Chem. Lett. 2011, 21, 1084-1088