Design, synthesis, and preliminary pharmacological evaluation of new quinoline derivatives as nicotinic ligands

Journal of Medicinal Chemistry

Volumn 50, Issue 20, 2007, Pages 4993-5002

  Guandalini, Luca ^a   Norcini, Monica ^a   Varani, Katia ^b   Pistolozzi, Marco ^c   Gotti, Cecilia ^d   Bazzicalupi, Carla ^a   Martini, Elisabetta ^a   Dei, Silvia ^a   Manetti, Dina ^a   Scapecchi, Serena ^a   Teodori, Elisabetta ^a   Bertucci, Carlo ^c   Ghelardini, Carla ^a   Romanelli, Maria Novella ^a  

^a UNIVERSITY OF FLORENCE   (Italy)

^b UNIVERSITY OF FERRARA   (Italy)

^c UNIVERSITY OF BOLOGNA   (Italy)

^d CNR   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

1 METHYL 2 PYRROLIDINYL 6 QUINOLINE; 6 (1 METHYLPYRROLIDIN 2 YL)QUINOLINE; LIGAND; MECAMYLAMINE; N,N,N TRIMETHYL 4 (QUINOLIN 6 YL) BUT 3 YN 1 AMMONIUM IODIDE; NICOTINE; NICOTINIC AGENT; NICOTINIC RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BRAIN CORTEX; CHOLINERGIC SYSTEM; CONTROLLED STUDY; DRUG DESIGN; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG SYNTHESIS; ENANTIOMER; ENANTIOSELECTIVITY; HOT PLATE TEST; MOUSE; NONHUMAN; RAT; RECEPTOR AFFINITY; STRUCTURE ACTIVITY RELATION; TRANS ISOMER;

ANALGESICS; ANIMALS; CEREBRAL CORTEX; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; LIGANDS; MICE; MOLECULAR CONFORMATION; PAIN MEASUREMENT; QUINOLINES; RADIOLIGAND ASSAY; RATS; RECEPTORS, NICOTINIC; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 34948865721     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm070325r     Document Type: Article

References (50)

1. Karlin, A. Emerging structure of the nicotinic acetylcholine receptors. Nat. Rev. Neurosci. 2002, 3, 102-114.
2. Gotti, C.; Clementi, F. Neuronal nicotinic receptors: From structure to pathology. Prog. Neurobiol. (Oxford) 2004, 74, 363-396.
3. Picciotto, M. R.; Caldarone, B. J.; Brunzell, D. H.; Zachariou, V.; Stevens, T. R.; King, S. L. Neuronal nicotinic acetylcholine receptor subunit knockout mice: Physiological and behavioral phenotypes and possible clinical implications. Pharmacol. Ther. 2001, 92, 89-108.
4. Jensen, A. A.; Frølund, B.; Liljefors, T.; Krogsgaard-Larsen, P. Neuronal nicotinic acetylcholine receptors: Structural revelations, target identifications, and therapeutic inspirations. J. Med. Chem. 2005, 48, 4705-4745.
5. Dani, J. A.; Bertrand, D. Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system. Annu. Rev. Pharmacol. Toxicol. 2007, 47, 699-729.
6. Gotti, C.; Riganti., L.; Vailati, S.; Clementi, F. Brain neuronal nicotinic receptors as new targets for drug discovery. Curr. Pharm. Des. 2006, 12, 407-428.
7. Romanelli, M. N.; Gratteri, P.; Guandalini, L.; Martini, E.; Bonaccini, C.; Gualtieri, F. Central nicotinic receptors: Structure, function, ligands, and therapeutic potential. ChemMedChem 2007, 2, 746-767.
8. Buccafusco, J. J.; Letchworth, S. R.; Bencherif, M.; Lippiello, P. M. Long-lasting cognitive improvement with nicotinic receptor agonists: Mechanisms of pharmacokinetic-pharmacodynamic discordance. Trends Pharmacol. Sci. 2005, 26, 352-360.
9. The asterisk used in the receptor nomenclature means that the receptor complex may contain additional subunits.
10. Jain, K. K. Modulators of nicotinic acetylcholine receptors as analgesics. Curr. Opin. Invest. Drugs 2004, 5, 76-81.
11. Guandalini, L.; Martini, E.; Dei, S.; Manetti, D.; Scapecchi, S.; Teodori, E.; Romanelli, M. N.; Varani, K.; Greco, G.; Spadola, L.; Novellino, E. Design of novel nicotinic ligands through 3D database searching. Bioorg. Med. Chem. 2005, 13, 799-807.
12. For the sake of clarity, we have adopted the same identification number for each family of compounds using the label a for secondary amines, b for tertiary amines, and c for ammonium salts.
13. Beers, W. H.; Reich, E. Structure and activity of acetylcholine. Nature 1970, 225, 917-922.
14. Glennon, R. A.; Herndon, J. L.; Dukat, M. Epibatidine-aided studies toward definition of a nicotine receptor pharmacophore. Med. Chem. Res. 1994, 4, 461-473.
15. Abreo, M. A.; Lin, N.-H.; Garvey, D. S.; Gunn, D. E.; Hettinger, A.-M.; Wasicak, J. T.; Pavlik, P. A.; Martin, Y. C.; Donnelly-Roberts, D. L.; Anderson, D. J.; Sullivan, J. P.; Williams, M.; Arneric, S. P.; Holladay, M. W. Novel 3-pyridyl ethers with subnanomolar affinity for central neuronal nicotinic acetylcholine receptors. J. Med. Chem. 1996, 39, 817-825.
16. Glennon, R. A.; Dukat, M. α4β2 nACh receptor pharmacophore models. Bioorg. Med. Chem. Lett. 2004, 14, 1841-1844.
17. Dull, G. M.; Bencherif, M.; Bhatti, B. S.; Deo, N. M.; Dobson, G. P.; Lippiello, P. M.; Miller, C. H.; Ravard, A.; Schmitt, J. D.; Crooks, P. A.; Caldwell, W. S. Book of Abstracts, August 23-27 1998, 216th National Meeting of the American Chemical Society, Boston, MA, 1998; American Chemical Society: Washington, DC, 1998.
18. Schmitt, J. D. Exploring the nature of molecular recognition in nicotinic acetylcholine receptors. Curr. Med. Chem. 2000, 7, 749-800.
19. Guandalini, L.; Martini, E.; Gratteri, P.; Ghelardini, C.; Varani, K.; Romanelli, M. N. Design, synthesis and binding affinity of new nicotinic ligands. ARKIVOC 2006, viii, 50-65.
20. Aceto, M. D.; Martin, B. R.; Uwaydah, I. M.; May, E. L.; Harris, L. S.; Izazola-Conde, C.; Dewey, W. L.; Bradshaw, T. J.; Vincek, W. C. Optically pure (+)-nicotine from (.H-.)-nicotine and biological comparisons with (-)-nicotine. J. Med. Chem. 1979, 22, 174-177.
21. Jacob, P. I. Resolution of (±)-5-bromonornicotine. Synthesis of (R)-and (S)-nornicotine of high enantiomeric purity. J. Org. Chem. 1982, 47, 4165-4167.
22. Bleicher, L. S.; Cosford, N. D. P.; Herbaut, A.; McCallum, J. S.; McDonald, I. A. A practical and efficient synthesis of the selective neuronal acetylcholine-gated ion channel agonist (S)-(-)-5-ethynyl-3-(1-methyl-2- pyrrolidinyl)pyridine maleate (SIB-1508Y). J. Org. Chem. 1998, 63, 1109-1118.
23. Dei, S.; Bellucci, C.; Buccioni, M.; Ferraroni, M.; Gualtieri, F.; Guandalini, L.; Manetti, D.; Matucci, R.; Romanelli, M. N.; Scapecchi, S.; Teodori, E. Synthesis and cholinergic affinity of diastereomeric and enantiomeric isomers of 1-methyl-2-(2-methyl-1,3-dioxolan-4-yl)-pyrrolidine, 1-methyl-2-(2-methyl-1,3-oxafhiolan-5-yl)pyrrolidine, and of their iodomethylates. Bioorg. Med. Chem. 2003, 11, 3153-3164.
24. Misaki, T.; Nagase, R.; Matsumoto, K.; Tanabe, Y. Ti-crossed-Claisen condensation between carboxylic esters and acid chlorides or acids: A highly selective and general method for the preparation of various α-keto esters. J. Am. Chem. Soc 2005, 127, 2854-2855.
25. Flack, H. D. On enantiomorph-polarity estimation. Acta Crystallogr., Sect. A 1983, A39, 876-881.
26. 4-phenylpiperazinium iodide (DMPP). J. Med. Chem. 2001, 44, 3946-3955.
27. Carbonnelle, E.; Sparatore, F.; Canu-Boido, C.; Salvagno, C.; Baldani-Guerra, B.; G., T.; Zwart, R.; Vijverberg, H.; Clementi, F.; Gotti, C. Nitrogen substitution modifies the activity of cytisine on neuronal nicotinic receptor subtypes. Eur. J. Pharmacol. 2003, 471, 85-96.
28. O'Callaghan, J. P.; Holtzman, S. G. Quantification of the analgesic activity of narcotic antagonists by a modified hot-plate procedure. J. Pharmacol. Exp. Ther. 1975, 192, 497-505.
29. Carroll, F. I.; Hu, X.; Navarro, H. A.; Deschamps, J.; Abdrakhmanova, G. R.; Damaj, M. I.; Martin, B. R. Synthesis and pharmacological characterization of nicotinic acetylcholine receptor properties of (+)- and (-)-pyrido-[3,4- b]homotropanes. J. Med. Chem. 2006, 49, 3244-3250.
30. Garvey, D. S.; Wasicak, J. T.; Decker, M. W.; Brioni, J. D.; Buckley, M. J.; Sullivan, J. P.; Carrera, G. M.; Holladay, M. W.; Arneric, S. P.; Williams, M. Novel isoxazoles which interact with brain cholinergic channel receptors have intrinsic cognitive enhancing and anxiolytic activities. J. Med. Chem. 1994, 37, 1055-1059.
31. 3H] nicotine binding by the enantiomers of nicotine, nornicotine and anatoxin-a in membranes and solubilized preparations of different brain regions of rat. Naunyn-Schmiedeberg's Arch. Pharmacol. 1993, 348, 28-34.
32. Bunnelle, W. H.; Dart, M. J.; Schrimpf, M. R. Design of ligands for the nicotinic acetylcholine receptors: The quest for selectivity. Curr. Top. Med. Chem. 2004, 4, 229-334.
33. Damaj, M. I.; Creasy, K. R.; Grove, A. D.; Rosecrans, J. A.; Martin, B. R. Pharmacological effects of epibatidine optical enantiomers. Brain Res. 1994, 664, 34-40.
34. The analgesic activity of rac-1b and rac-1c, after icv injection, have been reported in ref 19; analgesia was prevented by mecamylamine.
35. Rueter, L.; Decker, M. W.; Bitner, R. S. Improving the therapeutic window in the treatment of pain with nicotinic ligands. Drug Discovery Today: Therapeutic Strategies 2004, 1, 89-96.
36. Dogruer, D.; Lee, M.; Dukat, M.; Damaj, M. I.; Martin, B.; Glennon, R. A. 3-(4-Aminobutyn-1-yl)pyridines: Binding at α4β2 nicotinic cholinergic receptors. Bioorg. Med. Chem. Lett. 2004, 14, 523-526.
37. Elliott, R. L.; Kopecka, H.; Gunn, D. E.; Lin, N.-H.; Garvey, D. S.; Ryther, K. B.; Holladay, M. W.; Anderson, D. J.; Campbell, J. E.; Sullivan, J. P.; Buckley, M. J.; Gunther, K. L.; O'Neill, A. B.; Decker, M. W.; Arneric, S. P. 2-(Aryloxymethyl) azacyclic analogues as novel nicotinic acethylcholine receptor (nAChR) ligands. Bioorg. Med. Chem. Lett. 1996, 6, 2283-2288.
38. Cheng, Y.-X.; Dukat, M.; Dowd, M.; Fiedler, W.; Martin, B.; Damaj, M. I.; Glennon, R. A. Synthesis and binding of 6,7,8,9-tetrahydro-5H-pyrido[3, 4-d]azepine and related ring-opened analogs at central nicotinic receptors. Eur. J. Med. Chem. 1999, 34, 177-190.
39. Gündisch, D.; Andrä, M.; Munoz, L.; Tilotta, M. C. Synthesis and evaluation of phenylcarbamate derivatives as ligands for nicotinic acetylcholine receptors. Bioorg. Med. Chem. 2004, 12, 4953-4962.
40. Ragab, H. M.; Kim, J. S.; Dukat, M.; Navarro, H. A.; Glennon, R. A. Aryloxyethylamines: Binding at α7 nicotinic acetylcholine receptors. Bioorg. Med. Chem. Lett. 2006, 16, 4283-4286.
41. Gotti, C.; Zoli, M.; Clementi, F. Brain nicotinic acetylcholine receptors: native subtypes and their relevance. Trends Pharmacol. Sci. 2006, 27, 482-491.
42. Xiao, Y.; Kellar, K. J. The comparative pharmacology and upregulation of rat neuronal nicotinic receptor subtype binding sites stably expressed in transfected mammalian cells. J. Pharmacol. Exp. Ther. 2004, 310, 98-107.
43. Jensen, A. A.; Mikkelsen, I.; Frølund, B.; Brauner-Osborne, H.; Falch, E.; Krogsgaard-Larsen, P. Carbamoylcholine homologs: Novel and potent agonists at neuronal nicotinic acetylcholine receptors. Mol. Pharmacol. 2003, 64, 865-875.
44. Grinevich, V. P.; Letchworth, S. R.; Lindenberger, K. A.; Menager, J.; Mary, V.; Sadieva, K. A.; Buhlman, L. M.; Bohme, G. A.; Pradier, L.; Benavides, J.; Lukas, R. J.; Bencherif, M. Heterologous expression of human {alpha}6{beta}4{beta}3{alpha}5 nicotinic acetylcholine receptors: Binding properties consistent with their natural expression require quaternary subunit assembly including the {alpha}5 subunit. J. Pharmacol. Exp. Ther. 2005, 312, 619-626.
45. Mukhin, A. G.; Gundisch, D.; Horti, A. G.; Koren, A. O.; Tamagnan, G.; Kimes, A. S.; Chambers, J.; Vaupel, D. B.; King, S. L.; Picciotto, M. R.; Innis, R. B.; London, E. D. 5-Iodo-A-85380, an alpha 4beta 2 subtype-selective ligand for nicotinic acetylcholine receptors. Mol. Pharmacol. 2000, 57, 642-649.
46. 3H]norepinephrine release from mouse hippocampal synaptosomes. Mol. Pharmacol. 2006, 70, 967-976.
47. La Coste, W. Zur Kenntniss der halogenoderivate des chinolins. Chem. Ber. 1882, 15, 557-563.
48. CrysAlis RED, version 1.171; Oxford Diffraction, Ltd.: Abingdon, U.K.; pre23_10beta (release June 21, 2004, CrysAlis171.NET; compiled June 21, 2004, 12:00:08).
49. Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, G. L.; Giacovazzo, C.; Guagliardi, A.; Moliterni, A. G. G.; Polidori, G.; Spagna, R. SIR97: A new tool for crystal structure determination and refinement. J. Appl. Crystallogr. 1999, 32, 115-119.
50. Sheldrick, G. M. SHELXL-97, Göttingen, Germany, 1997.