Ligand based approach to L-type calcium channel by imidazo[2,1-b]thiazole- 1,4-dihydropyridines: From heart activity to brain affinity

Journal of Medicinal Chemistry

Volumn 56, Issue 10, 2013, Pages 3866-3877

  Locatelli, Alessandra ^a   Cosconati, Sandro ^b   Micucci, Matteo ^a   Leoni, Alberto ^a   Marinelli, Luciana ^c   Bedini, Andrea ^a   Ioan, Pierfranco ^a   Spampinato, Santi Mario ^a   Novellino, Ettore ^c   Chiarini, Alberto ^a   Budriesi, Roberta ^a  

^a UNIVERSITY OF BOLOGNA   (Italy)

^b SECOND UNIVERSITY OF NAPLES   (Italy)

^c UNIVERSITY OF NAPLES FEDERICO II   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

CALCIUM CHANNEL BLOCKING AGENT; CALCIUM CHANNEL L TYPE; DIETHYL 4 (6 (2,5 DIMETHOXYPHENYL)IMIDAZO[2,1 B]THIAZOL 5 YL) 2,6 DIMETHYL 1,4 DIHYDROPYRIDINE 3,5 DICARBOXYLATE; DIHYDROPYRIDINE DERIVATIVE; DIMETHYL 2,6 DIMETHYL 4 (2 METHYL 6 (PYRIDIN 2 YL)IMIDAZO[2,1 B]THIAZOL 5 YL) 1,4 DIHYDROPYRIDINE 3,5 DICARBOXYLATE; DIMETHYL 2,6 DIMETHYL 4 (2 METHYL 6 (PYRIDIN 3 YL)IMIDAZO[2,1 B]THIAZOL 5 YL) 1,4 DIHYDROPYRIDINE 3,5 DICARBOXYLATE; DIMETHYL 2,6 DIMETHYL 4 (2 METHYL 6 (PYRIDIN 4 YL)IMIDAZO[2,1 B]THIAZOL 5 YL) 1,4 DIHYDROPYRIDINE 3,5 DICARBOXYLATE; DIMETHYL 2,6 DIMETHYL 4 (2 METHYL 6 (THIOPHEN 2 YL)IMIDAZO [2,1 B]THIAZOL 5 YL) 1,4 DIHYDROPYRIDINE 3,5 DICARBOXYLATE; DIMETHYL 2,6 DIMETHYL 4 (2 METHYL 6 (THIOPHEN 3 YL)IMIDAZO[2,1 B]THIAZOL 5 YL) 1,4 DIHYDROPYRIDINE 3,5 DICARBOXYLATE; DIMETHYL 2,6 DIMETHYL 4 (6 (PYRIDIN 2 YL)IMIDAZO[2,1 B]THIAZOL 5 YL) 1,4 DIHYDROPYRIDINE 3,5 DICARBOXYLATE; DIMETHYL 2,6 DIMETHYL 4 (6 (PYRIDIN 3 YL)IMIDAZO[2,1 B]THIAZOL 5 YL) 1,4 DIHYDROPYRIDINE 3,5 DICARBOXYLATE; DIMETHYL 2,6 DIMETHYL 4 (6 (PYRIDIN 4 YL)IMIDAZO[2,1 B]THIAZOL 5 YL) 1,4 DIHYDROPYRIDINE 3,5 DICARBOXYLATE; DIMETHYL 2,6 DIMETHYL 4 (6 (THIOPHEN 2 YL)IMIDAZO[2,1 B] THIAZOL 5 YL) 1,4 DIHYDROPYRIDINE 3,5 DICARBOXYLATE; DIMETHYL 2,6 DIMETHYL 4 (6 (THIOPHEN 3 YL)IMIDAZO[2,1 B] THIAZOL 5 YL) 1,4 DIHYDROPYRIDINE 3,5 DICARBOXYLATE; DIMETHYL 4 (6 (2,5 DICHLOROTHIOPHEN 3 YL) 2 METHYLIMIDAZO[2,1 B]THIAZOL 5 YL) 2,6 DIMETHYL 1,4 DIHYDROPYRIDINE 3,5 DICARBOXYLATE; DIMETHYL 4 (6 (2,5 DICHLOROTHIOPHEN 3 YL)IMIDAZO[2,1 B]THIAZOL 5 YL) 2,6 DIMETHYL 1,4 DIHYDROPYRIDINE 3,5 DICARBOXYLATE; UNCLASSIFIED DRUG;

ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; CARDIOVASCULAR EFFECT; CONTROLLED STUDY; DRUG SYNTHESIS; GUINEA PIG; HEART ATRIUM; HEART VENTRICLE; IN VITRO STUDY; MOLECULAR MODEL; NONHUMAN; PHYSICAL CHEMISTRY; STRUCTURE ACTIVITY RELATION;

ANIMALS; CALCIUM CHANNEL BLOCKERS; CALCIUM CHANNELS; CALCIUM CHANNELS, L-TYPE; CEREBRAL CORTEX; COMPUTER SIMULATION; DIHYDROPYRIDINES; GUINEA PIGS; HEART; HEART RATE; IMIDAZOLES; MODELS, MOLECULAR; MUSCLE, SMOOTH; MYOCARDIAL CONTRACTION; MYOCARDIUM; MYOCYTES, CARDIAC; RATS; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZOLES;

EID: 84878038726     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm301839q     Document Type: Article

References (29)

1. Triggle, D. J. L-Type calcium channels Curr. Pharm. Des. 2006, 12, 443-457
2. Catterall, W. A.; Perez-Reyes, E.; Snutch, T. P.; Striessnig, J. International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels Pharmacol. Rev. 2005, 57, 411-425
3. Zuccotti, A.; Clementi, S.; Reinbothe, T.; Torrente, A.; Vandael, D. H.; Pirone, A. Structural and functional differences between L-type calcium channels: crucial issues for future selective targeting Trends Pharmacol. Sci. 2011, 6, 366-375
4. Fleckenstein, A. Specific pharmacology of calcium in myocardium, cardiac pacemakers, and vascular smooth muscle Annu. Rev. Pharmacol. Toxicol. 1977, 17, 149-166
5. 2+ channels Trends Pharmacol. Sci. 1998, 19, 108-115
6. McDonough, S. I., Ed. Calcium Channels Pharmacology; Kluwer Academic/Plenum Publishers: New York, 2004.
7. Triggle, D. J. Calcium channel antagonists: clinical uses-past, present and future Biochem. Pharmacol. 2007, 74, 1-9
8. 2+- channels: contribution of Ca(V)1.3 and Ca(V)1.2 isoforms Neuroscience 2006, 139, 1005-1015
9. Sinnegger-Brauns, M. J.; Huber, I. G.; Koschak, A.; Wild, C.; Obermair, G. J.; Einzinger, U.; Hoda, J. C.; Sartori, S. B.; Striessnig, J. Expression and 1,4-dihydropyridine-binding properties of brain L-type calcium channel isoforms Mol. Pharmacol. 2009, 75, 407-414
10. Ioan, P.; Carosati, E.; Micucci, M.; Cruciani, G.; Broccatelli, F.; Zhorov, B. S.; Chiarini, A.; Budriesi, R. 1,4-Dihydropyridine Scaffold in Medicinal Chemistry, The Story So Far and Perspectives. Part 1: Action in Ion Channels and GPCRs Curr. Med. Chem. 2011, 18, 4901-4922
11. Carosati, E.; Ioan, P.; Micucci, M.; Broccatelli, F.; Cruciani, G.; Zhorov, B. S.; Chiarini, A.; Budriesi, R. 1,4-Dihydropyridine Scaffold in Medicinal Chemistry, The Story So Far and Perspectives. Part 2: Action in Other Targets and Antitargets Curr. Med. Chem. 2012, 19, 4306-4323
12. 2+ channel isoforms for brain function Biochem. Soc. Trans. 2006, 34, 903-909
13. Budriesi, R.; Ioan, P.; Leoni, A.; Locatelli, A.; Cosconati, S.; Ugenti, M. P.; Andreani, A.; Di Toro, R.; Bedini, A.; Spampinato, S.; Marinelli, L.; Novellino, E.; Chiarini, A. Imidazo[2,1- b ]thiazole System: A Scaffold Endowing Dihydropyridines With Selective Cardiodepressant Activity J. Med. Chem. 2008, 51, 1592-1600
14. Phillips, A. P. Hantzsch's pyridine synthesis J. Am. Chem. Soc. 1949, 71, 4003-4007
15. Andreani, A.; Rambaldi, M.; Andreani, F.; Bossa, R.; Galatulas, I. 6-Pyridinylimidazo[2,1- b ]thiazoles and Thiazolines as Potential Cardiotonic Agents Eur. J. Med. Chem. 1985, 20, 93-94
16. Andreani, A.; Burnelli, S.; Granaiola, M.; Leoni, A.; Locatelli, A.; Morigi, R.; Rambaldi, M.; Varoli, L.; Farruggia, G.; Stefanelli, C.; Masotti, L.; Kunkel, M. W. Synthesis and Antitumor Activity of Guanylhydrazones from 6-(2,4-Dichloro-5-nitrophenyl)imidazo[2,1- b ]thiazoles and 6-Pyridilimidazo[2, 1- b ]thiazoles J. Med. Chem. 2006, 49, 7897-7901
17. Andreani, A.; Burnelli, S.; Granaiola, M.; Leoni, A.; Locatelli, A.; Morigi, R.; Rambaldi, M.; Varoli, L.; Calonghi, N.; Cappadone, C.; Farruggia, G.; Zini, M.; Stefanelli, C.; Masotti, L.; Radin, N. S.; Shoemaker, R. H. New Antitumor Imidazo[2,1- b ]thiazole Guanylhydrazones and Analogues J. Med. Chem. 2008, 51, 809-816
18. Andreani, A.; Rambaldi, M.; Locatelli, A.; Bossa, R.; Galatulas, I.; Ninci, M. Synthesis and cardiotonic activity of 2,5-dimethoxyphenylimidazo[2,1- b ]thiazoles Eur. J. Med. Chem. 1992, 27, 431-433
19. Budriesi, R.; Ioan, P.; Leoni, A.; Pedemonte, N.; Locatelli, A.; Micucci, M.; Chiarini, A.; Galietta, L. J. Cystic Fibrosis: A New Target for 4-Imidazo[2,1- b ]thiazole-1,4-DHPs J. Med. Chem. 2011, 54, 3885-3094
20. Tallarida, R. J.; Murray, R. B. Manual of Pharmacologic Calculations with Computer Programs, 2nd ed.; Springer-Verlag: New York, 1987.
21. Motulsky, H.; Christopoulos, A. Fitting Models to Biological Data Using Linear and Nonlinear Regression, 2003, www.graphpad.com. Accessed on 1/12/2011.
22. Motulsky, H. J. Prism 5 Statistics Guide; GraphPad Software Inc.: San Diego, CA, 2007; www.graphpad.com. Accessed on 1/12/2011.
23. GraphPad, version 3.0; GraphPad Software, Inc.: San Diego, CA.
24. Tarabová, B.; Nováková, M.; Lacinová, L. Haloperidol moderately inhibits cardiovascular L-type calcium current Gen. Physiol. Biophys. 2009, 28 (3) 249-529
25. 2+ channel: model construction and docking calculations J. Med. Chem. 2007, 50, 1504-1513
26. Pettersen, E. F.; Goddard, T. D.; Huang, C. C.; Couch, G. S.; Greenblatt, D. M.; Meng, E. C.; Ferrin, T. E. UCSF Chimera-a visualization system for exploratory research and analysis J. Comput. Chem. 2004, 25, 1605-1612
27. Limongelli, V.; Marinelli, L.; Cosconati, S.; La Motta, C.; Sartini, S.; Mugnaini, L.; Da Settimo, F.; Novellino, E.; Parrinello, M. Sampling protein motion and solvent effect during ligand binding Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 1467-1472
28. Limongelli, V.; Bonomi, M.; Marinelli, L.; Gervasio, F. L.; Cavalli, A.; Novellino, E.; Parrinello, M. Molecular basis of cyclooxygenase enzymes (COXs) selective inhibition Proc. Natl. Acad. Sci. U. S. A. 2010, 107, 5411-5416
29. Lo Monte, F.; Kramer, T.; Gu, J.; Anumala, U. R.; Marinelli, L.; La Pietra, V.; Novellino, E.; Franco, B.; Demedts, D.; Van Leuven, F.; Fuertes, A.; Dominguez, J. M.; Plotkin, B.; Eldar-Finkelman, H.; Schmidt, B. Identification of Glycogen Synthase Kinase-3 Inhibitors with a Selective Sting for Glycogen Synthase Kinase-3α J. Med. Chem. 2012, 55, 4407-4424