Strategies to reduce hERG K+ channel blockade. Exploring heteroaromaticity and rigidity in novel pyridine analogues of dofetilide

Journal of Medicinal Chemistry

Volumn 56, Issue 7, 2013, Pages 2828-2840

  Carvalho, João F S ^a   Louvel, Julien ^a   Doornbos, Maarten L J ^a   Klaasse, Elisabeth ^a   Yu, Zhiyi ^a   Brussee, Johannes ^a   Ijzerman, Adriaan P ^a  

^a LEIDEN UNIVERSITY   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIARRHYTHMIC AGENT; DOFETILIDE; POTASSIUM CHANNEL BLOCKING AGENT; POTASSIUM CHANNEL HERG; PYRIDINE DERIVATIVE;

ARTICLE; BINDING AFFINITY; BINDING ASSAY; CHANNEL GATING; CHEMICAL MODIFICATION; CONFORMATIONAL TRANSITION; DRUG DESIGN; DRUG PROTEIN BINDING; DRUG SYNTHESIS; HUMAN; HUMAN CELL; LIGAND BINDING; PATCH CLAMP; STRUCTURE ACTIVITY RELATION;

ETHER-A-GO-GO POTASSIUM CHANNELS; HEK293 CELLS; HUMANS; PATCH-CLAMP TECHNIQUES; PHENETHYLAMINES; POTASSIUM CHANNEL BLOCKERS; RADIOLIGAND ASSAY; SULFONAMIDES;

EID: 84876256428     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm301564f     Document Type: Article

References (40)

1. + Channel Cell 2005, 123, 463-475
2. Sanguinetti, M. C.; Tristani-Firouzi, M. hERG Potassium Channels and Cardiac Arrhythmia Nature 2006, 440, 463-469
3. Valentin, J.-P.; Hammond, T. Safety and Secondary Pharmacology: Successes, Threats, Challenges and Opportunities J. Pharmacol. Toxicol. Methods 2008, 58, 77-87
4. + Channel Blockade by Synthesis and Biological Evaluation of Dofetilide Analogues ChemMedChem 2009, 4, 1722-1732
5. + Channel Blockade: Synthesis and Biological Evaluation of E-4031 Analogues ChemMedChem 2012, 7, 107-113
6. Ponti, F. D.; Poluzzi, E.; Cavalli, A.; Recanatini, M.; Montanaro, N. Safety of Non-Antiarrhythmic Drugs that Prolong the QT Interval or Induce Torsade de Pointes: An Overview Drug Safety 2002, 25, 263-286
7. Aronov, A. M. Common Pharmacophores for Uncharged Human Ether-a-go-go-Related Gene (hERG) Blockers J. Med. Chem. 2006, 49, 6917-6921
8. Carvalho, J. F. S.; Silva, M. M. C.; Sá e Melo, M. L. Highly Efficient Epoxidation of Unsaturated Steroids Using Magnesium Bis(monoperoxyphthalate) Hexahydrate Tetrahedron 2009, 65, 2773-2781
9. Manchester, J.; Walkup, G.; Rivin, O.; You, Z. Evaluation of pKa Estimation Methods on 211 Druglike Compounds J. Chem. Inf. Model. 2010, 50, 565-571
10. Zachariae, U.; Giordanetto, F.; Leach, A. G. Side Chain Flexibilities in the Human Ether-a-go-go Related Gene Potassium Channel (hERG) Together with Matched-Pair Binding Studies Suggest a New Binding Mode for Channel Blockers J. Med. Chem. 2009, 52, 4266-4276
11. Lavrado, J.; Gani, K.; Nobre, P. A.; Santos, S. A.; Figueiredo, P.; Lopes, D.; Rosário, V.; Gut, J.; Rosenthal, P. J.; Moreira, R.; Paulo, A. Bis-alkylamine Quindolone Derivatives as New Antimalarial Leads Bioorg. Med. Chem. Lett. 2010, 20, 5634-5637
12. Alptüzün, V.; Parlar, S.; TaşlI, H.; Erciyas, E. Synthesis and Antimicrobial Activity of Some Pyridinium Salts Molecules 2009, 14, 5203-5215
13. Robertson, L.; Hartley, R. C. Synthesis of N-Arylpyridinium Salts Bearing a Nitrone Spin Trap as Potential Mitochondria-Targeted Antioxidants Tetrahedron 2009, 65, 5284-5292
14. Musilek, K.; Kucera, J.; Jun, D.; Dohnal, V.; Opletalova, V.; Kuca, K. Monoquaternary Pyridinium Salts with Modified Side Chain-Synthesis and Evaluation on Model of Tabun- and Paraoxon-Inhibited Acetylcholinesterase Bioorg. Med. Chem. 2008, 16, 8218-8223
15. + Channel HERG Mol. Pharmacol. 2001, 59, 122-126
16. Redfern, W. S.; Carlsson, L.; Davis, A. S.; Lynch, W. G.; MacKenzie, I.; Palethorpe, S.; Siegl, P. K. S.; Strang, I.; Sullivan, A. T.; Wallis, R.; Camm, A. J.; Hammond, T. G. Relationships between Preclinical Cardiac Electrophysiology, Clinical QT Interval Prolongation and Torsade de Pointes for a Broad Range of Drugs: Evidence for a Provisional Safety Margin in Drug Development Cardiovasc. Res. 2003, 58, 32-45
17. De Bruin, M. L.; Pettersson, M.; Meyboom, R. H. B.; Hoes, A. W.; Leufkens, H. G. M. Anti-HERG Activity and the Risk of Drug-Induced Arrhythmias and Sudden Death Eur. Heart J. 2005, 26, 590-597
18. Webster, R.; Leishman, D.; Walker, D. Towards a Drug Concentration Effect Relationship for QT Prolongation and Torsades de Pointes Curr. Opin. Drug Discovery Dev. 2002, 5, 116-126
19. Jamieson, C.; Moir, E. M.; Rankovic, Z.; Wishart, G. Medicinal Chemistry of hERG Optimizations: Highlights and Hang-Ups J. Med. Chem. 2006, 49, 5029-5046
20. + Channel Blockers J. Med. Chem. 2002, 45, 3844-3853
21. + Channel Blockers Bioorg. Med. Chem. 2004, 12, 2307-2315
22. Du, L.-P.; Tsai, K.-C.; Li, M.-Y.; You, Q.-D.; Xia, L. The Pharmacophore Hypotheses of IKr Potassium Channel Blockers: Novel Class III Antiarrhythmic Agents Bioorg. Med. Chem. Lett. 2004, 14, 4771-4777
23. Zacharias, N.; Dougherty, D. A. Cation-π Interactions in Ligand Recognition and Catalysis Trends Pharmacol. Sci. 2002, 23, 281-287
24. Fernandez, D.; Ghanta, A.; Kauffman, G. W.; Sanguinetti, M. C. Physicochemical Features of the hERG Channel Drug Binding Site J. Biol. Chem. 2004, 279, 10120-10127
25. + Currents in Rabbit Schwann Cells J. Physiol. 1991, 433, 183-205
26. Choquet, D.; Korn, H. Mechanism of 4-Aminopyridine Action on Voltage-Gated Potassium Channels in Lymphocytes J. Gen. Physiol. 1992, 99, 217-240
27. Kameda, M.; Kobayashi, K.; Ito, H.; Miyazoe, H.; Tsujino, T.; Nakama, C.; Kawamoto, H.; Ando, M.; Ito, S.; Suzuki, T.; Kanno, T.; Tanaka, T.; Tahara, Y.; Tani, T.; Tanaka, S.; Tokita, S.; Sato, N. Optimization of a Series of 2,4-Diaminopyridines as Neuropeptide Y Y1 Receptor Antagonists with Reduced hERG Activity Bioorg. Med. Chem. Lett. 2009, 19, 4325-4329
28. Owen, D. R.; Rodriguez-Lens, M.; Corless, M. D.; Gaulier, S. M.; Horne, V. A.; Kinloch, R. A.; Maw, G. N.; Pearce, D. W.; Rees, H.; Ringer, T. J.; Ryckmans, T.; Stammen, B. L. C. 2,4-Diaminopyridine δ-Opioid Receptor Agonists and Their Associated hERG Pharmacology Bioorg. Med. Chem. Lett. 2009, 19, 1702-1706
29. Perry, M.; Stansfeld, P. J.; Leaney, J.; Wood, C.; de Groot, M. J.; Leishman, D.; Sutcliffe, M. J.; Mitcheson, J. S. Drug Binding Interactions in the Inner Cavity of hERG Channels: Molecular Insights from Structure-Activity Relationships of Clofilium and Ibutilide Analogs Mol. Pharmacol. 2006, 69, 509-519
30. Scheel, O.; Himmel, H.; Rascher-Eggstein, G.; Knott, T. Introduction of a Modular Automated Voltage-Clamp Platform and Its Correlation with Manual Human Ether-à-go-go Related Gene Voltage-Clamp Data Assay Drug Dev. Technol. 2011, 9, 600-607
31. Lukevits, é. Pyridine Derivatives in the Drug Arsenal (150 years of pyridine chemistry) Chem. Heterocycl. Compd. 1995, 31, 639-650
32. Chaubey, A.; Pandeya, S. N. Pyridine: a Versatile Nucleuse in Pharmaceutical Field Asian J. Pharm. Clin. Res. 2011, 4, 5-8
33. Kumar, S.; Sharma, P. K.; Dudhe, R.; Kumar, N. Pyridine: Potential for Biological Activities J. Chronother. Drug Delivery 2011, 2, 71-78
34. Cavalli, A.; Buonfiglio, R.; Ianni, C.; Masetti, M.; Ceccarini, L.; Caves, R.; Chang, M. W. Y.; Mitcheson, J. S.; Roberti, M.; Recanatini, M. Computational Design and Discovery of "Minimally Structured" hERG Blockers J. Med. Chem. 2012, 55, 4010-4014
35. Cho, Y. S.; Whitehead, L.; Li, J.; Chen, C. H. T.; Jiang, L.; Vögtle, M.; Francotte, E.; Richert, P.; Wagner, T.; Traebert, M.; Lu, Q.; Cao, X.; Dumotier, B.; Fejzo, J.; Rajan, S.; Wang, P.; Yan-Neale, Y.; Shao, W.; Atadja, P.; Shultz, M. Conformational Refinement of Hydroxamate-Based Histone Deacetylase Inhibitors and Exploration of 3-Piperidin-3-ylindole Analogues of Dacinostat (LAQ824) J. Med. Chem. 2010, 53, 2952-2963
36. Patrick, G. L. An Introduction to Medicinal Chemistry; Oxford University Press: New York, 2001.
37. Lämsä, M.; Kiviniemi, S.; Kettukangas, E.-R.; Nissinen, M.; Pursiainen, J.; Rissanen, K. Synthesis and Characterization of New Aromatic Tweezers and Complex Formation with Tropylium Ion in 1,2-Dichloroethane J. Phys. Org. Chem. 2001, 14, 551-558
38. Yamaguchi, Y.; Kobayashi, S.; Wakamiya, T.; Matsubara, Y.; Yoshida, Z.-i. Banana-Shaped Oligo(aryleneethynylene)s: Synthesis and Light-Emitting Characteristics Angew. Chem., Int. Ed. 2005, 44, 7040-7044
39. Zheng, G.; Dwoskin, L. P.; Deaciuc, A. G.; Norrholm, S. D.; Crooks, P. A. Defunctionalized Lobeline Analogues: Structure-Activity of Novel Ligands for the Vesicular Monoamine Transporter J. Med. Chem. 2005, 48, 5551-5560
40. Sisido, K.; Yosikawa, Y. The Organic Reactions with Aluminum Chloride. XX. The Action of Aluminum Chloride upon Ethylene Chloride J. Am. Chem. Soc. 1948, 70, 1608-1609