Discovery of a novel class of imidazo[1,2-a ]pyridines with potent PDGFR activity and oral bioavailability

ACS Medicinal Chemistry Letters

Volumn 5, Issue 1, 2014, Pages 78-83

  Hicken, Erik J ^a   Marmsater, Fred P ^a   Munson, Mark C ^a   Schlachter, Stephen T ^a   Robinson, John E ^a   Allen, Shelley ^a   Burgess, Laurence E ^a   Delisle, Robert Kirk ^a   Rizzi, James P ^a   Topalov, George T ^a   Zhao, Qian ^a   Hicks, Julie M ^a   Kallan, Nicholas C ^a   Tarlton, Eugene ^a   Allen, Andrew ^a   Callejo, Michele ^a   Cox, April ^a   Rana, Sumeet ^a   Klopfenstein, Nathalie ^a   Woessner, Richard ^a   Lyssikatos, Joseph P ^a   more..

^a Department of Drug Discovery Array BioPharma ^*  (United States)

Author keywords

fluorine; fluoro piperidine; Pgp; Platelet derived growth factor

Indexed keywords

IMIDAZO[1,2 A]PYRIDINE DERIVATIVE; MULTIDRUG RESISTANCE PROTEIN; PLATELET DERIVED GROWTH FACTOR RECEPTOR;

ARTICLE; DRUG BIOAVAILABILITY; DRUG STRUCTURE; DRUG SYNTHESIS; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION;

EID: 84892623447     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml4003953     Document Type: Article

References (27)

1. Lewis, N. L. The platelet-derived growth factor receptor as a therapeutic target Curr. Oncol. Rep. 2007, 9, 89-95
2. Board, R.; Jayson, G. C. Platelet-derived growth factor receptor (PDGFR): A target for anticancer therapeutics Drug Resist. Updates 2005, 8, 75-83
3. Wong, N. A. C. S.; Mangwana, S. KIT and PDGFRα mutational analyses of mixed cell-type gastrointestinal stromal tumors Histopathology 2007, 51, 758-762
4. Joyce, J. A. Therapeutic targeting of the tumor microenvironment Cancer Cell 2005, 7, 513-520
5. Huang, J.; Soffer, S. Z.; Kim, E. S.; McCrudden, K. W.; Huang, J.; New, T.; Manley, C. A.; Middlesworth, W.; O'Toole, K.; Yamashiro, D. J.; Kandel, J. Vascular remodeling marks tumors that recur during chronic suppressionof angiogenesis J. Mol. Cancer Res. 2004, 2, 36-42
6. Bonner, J. C.; Lindroos, P. M.; Rice, A. B.; Moomaw, C. R.; Morgan, D. L. Induction of PDGF receptor-α in rat myofibroblasts during pulmonary fibrogenesis in vivo Am. J. Physiol.: Lung Cell. Mol. Physiol. 1998, 274, L72-L80
7. Matsuno, K.; Nakajima, T.; Ichimura, M.; Giese, N. A.; Yu, J.-C.; Lokker, N. A.; Ushiki, J.; Ide, S.; Oda, S.; Nomoto, Y. Potent and selective inhibitors of PDGFR receptor phosphorylation. 2. Synthesis, structure activity relationship, improvement of aqueous solubility, and biological effects of 4-[4-(N-substituted(thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline derivatives J. Med. Chem. 2002, 45, 4513-4523
8. Roberts, W. G.; Whalen, P. M.; Soderstrom, E.; Moraski, G.; Lyssikatos, J. P.; Wang, H.-F.; Cooper, B.; Baker, D. A.; Savage, D.; Dalvie, D.; Atherton, J. A.; Ralston, S.; Szewc, R.; Kath, J. C.; Lin, J.; Soderstrom, C.; Tkalcevic, G.; Cohen, B. D.; Pollack, V.; Barth, W.; Hungerford, W.; Ung, E. Antiangiogenic and antitumor activity of a selective PDGFR tyrosine kinase inhibitor, CP-673,451 Cancer Res. 2005, 65, 957-966
9. For a more recent review see: Dai, Y. Platelet-derived growth factor receptor kinase inhibitors: a review of the recent patent literature Expert Opin. Ther. Patents 2010, 20, 885-907
10. Robinson, D. R.; Wu, Y.-M.; Lin, S.-F. The protein tyrosine kinase family of the human genome Oncogene 2000, 19, 5548-557
11. Ullrich, A.; Schlessinger, J. Signal transduction by receptors with tyrosine activity Cell 1990, 61, 203-212
12. Kaipainen, A.; Korhonen, J.; Pajusola, K.; Aprelikova, O.; Persico, M. G.; Terman, B. I.; Alitalo, K. The related FLT4, FLT1, and KDR receptor tyrosine kinases show distinct expression patterns in human endothelial cells J. Exp. Med. 1993, 178, 2077-2088
13. Allen, S.; Greschuk, J. M.; Kallan, N. C.; Marmsater, F. P.; Munson, M. C.; Rizzi, J. P.; Robinson, J. E.; Schlachter, S. P.; Topalov, G. T.; Zhao, Q. Imidazo[1,2-A] Pyridine Compounds as Receptor Tyrosine Kinase Inhibitors. International Patent Application WO 2008/124323 A1, 2008.
14. Huang, X.; Buchwald, S. L. New ammonia equivalents for the Pd-catalyzed amination of aryl halides Org. Lett. 2001, 3, 3417-3419
15. Touré, B. B.; Lane, B. S.; Sames, D. Catalytic C-H arylation of SEM-protected azoles with palladium complexes of NHCs and phosphines Org. Lett. 2006, 8, 1979-1982
16. Koubachi, J.; El Kazzouli, S.; Berteina-Raboin, S.; Mouaddib, A.; Guillaumet, G. Regioselective palladium-catalyzed arylation and heteroarylation of imidazo[1,2-a]pyridines Synlett 2006, 19, 3237-3242
17. Faller, B.; Urban, L.; Mannhold, R. Hit and Lead Profiling: Identification and Optimization of Drug-Like Molecules; Wiley-VCH: Berlin, Germany, 2009.
18. Kerns, E. H.; Di, L. Drug-Like Properties: Concepts, Structure Design and Methods: from ADME to Toxicity Optimization; Academic Press: New York, 2008.
19. Gleeson, M. P. Generation of a set of simple, interpretable ADMET rules of thumb J. Med. Chem. 2008, 51, 817-834
20. Thomas, V. H.; Bhattachar, S.; Hitchingham, L.; Zocharski, P.; Naath, M.; Surendran, N.; Stoner, C. L.; El-Kattan, A. The road map to oral bioavailability: an industrial perspective Expert Opin. Drug Metab. Toxicol. 2006, 2, 591-608
21. Lerchner, A.; Machauer, R.; Betschart, C.; Veenstra, S.; Rueeger, H.; McCarthy, C.; Tintelnot-Blomley, M.; Jaton, A.-L.; Rabe, S.; Desrayaud, S.; Enz, A.; Staufenbiel, M.; Paganetti, P.; Rondeau, J.-M.; Neumann, U. Macrocyclic BACE-1 inhibitors acutely reduce Aβ in brain after po application Bioorg. Med. Chem. Lett. 2010, 20, 603-607
22. Su, D.-S.; Lim, J. L.; Tinney, E.; Wan, B.-L.; Murphy, K. L.; Reiss, D. R.; Harrell, C. M.; O'Malley, S. S.; Ransom, R. W.; Chang, R. S. L.; Pettibone, D. J.; Yu, J.; Tang, C.; Prueksaritanont, T.; Freidinger, R. M.; Bock, M. G.; Anthony, N. J. 2-Aminobenzophenones as a novel class of bradykinin B1 receptor antagonists J. Med. Chem. 2008, 51, 3946-3952
23. Cox, C. D.; Breslin, M. J.; Whitman, D. B.; Coleman, P. J.; Garbaccio, R. M.; Fraley, M. E.; Zrada, M. M.; Buser, C. A.; Walsh, E. S.; Hamilton, K.; Lobell, R. B.; Tao, W.; Abrams, M. T.; South, V. J.; Huber, H. E.; Kohl, N. E.; Hartman, G. D. Kinesin spindle protein (KSP) inhibitors. Part V: Discovery of 2-propylamino-2,4-diaryl-2,5-dihydropyrroles as potent, water-soluable KSP inhibitors, and modulation of their basicity by b-fluorination to overcome cellular efflux by P-glycoprotein Bioorg. Med. Chem. Lett. 2007, 17, 2697-2702
24. Morgenthaler, M.; Schweizer, E.; Hoffmann-Roder, A.; Benini, F.; Martin, R. E.; Jaeschke, G.; Wagner, B.; Fischer, H.; Bendels, S.; Zimmerli, D.; Schneider, J.; Diederich, F.; Kansy, M.; Muller, K. Predicting and tuning physicochemical properties in lead optimization: Amine basicities ChemMedChem 2007, 2, 1100-1115
25. 1D receptor ligands with improved pharmacokinetic profiles J. Med. Chem. 1999, 42, 2087-2104
26. Meanwell, N. A. Synopsis of some recent tactical application of bioisosteres in drug design J. Med. Chem. 2011, 54, 2529-2591
27. Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Fluorine in medicinal chemistry Chem. Soc. Rev. 2008, 37, 320-330