Coaxing a pyridine nucleus to give up its aromaticity: Synthesis and pharmacological characterization of novel conformationally restricted analogues of nicotine and anabasine

Journal of Medicinal Chemistry

Volumn 47, Issue 27, 2004, Pages 6691-6701

  Sarkar, Tarun K ^a   Basak, Sankar ^a   Wainer, Irving ^b   Moaddel, Ruin ^b   Yamaguchi, Rika ^b   Jozwiak, Krzysztof ^b   Chen, Hui Ting ^c   Lin, Chun Cheng ^c  

^a INDIAN INSTITUTE OF TECHNOLOGY   (India)

^b NATIONAL INSTITUTE ON AGING   (United States)

^c INSTITUTE OF CHEMISTRY   (Taiwan)

Author keywords

[No Author keywords available]

Indexed keywords

ANABASINE DERIVATIVE; CHOLINERGIC RECEPTOR BLOCKING AGENT; CHOLINERGIC RECEPTOR STIMULATING AGENT; NICOTINE DERIVATIVE; NICOTINIC AGENT; PYRIDINE DERIVATIVE; PYRROLIDINE DERIVATIVE;

ARTICLE; BINDING AFFINITY; DIELS ALDER REACTION; DRUG CONFORMATION; DRUG SYNTHESIS; MOLECULAR INTERACTION; STRUCTURE ACTIVITY RELATION;

ANABASINE; CRYSTALLOGRAPHY, X-RAY; MOLECULAR CONFORMATION; NICOTINE; RECEPTORS, NICOTINIC; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 11144246890     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm049707c     Document Type: Article

References (69)

1. Romanelli, M. N.; Gualtieri, F. Cholinergic nicotinic receptors: competitive ligands, allosteric modulators, and their potential applications. Med. Res. Rev. 2003, 23, 393-426.
2. Olesen, P. H.; Tønder, J. E. Agonists at the α4β2 nicotinic acetylcholine receptors: structure-activity relationships and molecular modeling. Curr. Med. Chem. 2001, 8, 651-674.
3. Sharples, C. G. V.; Wonnacott, S. Neuronal nicotinic receptors Tocris Rev. 2001, No. 19, 1-12.
4. Holladay, M. W.; Dart, M. J.; Lynch, J. K. Neuronal nicotinic acetylcholine receptors as targets for drug discovery. J. Med. Chem. 1997, 40, 4169-4194.
5. McDonald, I. A.; Vernier, J.-M.; Cosford, N.; Corey-Naeve, J. Neuronal nicotinic acetylcholine receptor agonists. Curr. Pharm. Des. 1996, 2, 357-366.
6. Glennon, R. A.; Dukat, M. Nicotinic receptor ligands. Med. Chem. Res. 1996, 6, 465-486.
7. Bannon, A. W.; Decker,. W.; Holladay, M. W.; Curzon, P.; Donnelly-Roberts, D.; Puttfarcken, P. S.; Bitner, R. S.; Diaz, A.; Dickenson, A. H.; Porsolt, R. D.; Williams, M.; Arneric, S. P. Broad-spectrum, nonopioid analgesic activity by selective modulation of neuronal nicotinic acetylcholine receptors. Science 1998, 279, 77-81.
8. Newhouse, P. A.; Sunderland, T.; Tariot, P. N.; Blumhardt, C. L.; Weingartner, H.; Mellow, A.; Murphey, D. L. Intravenous nicotine in Alzheimer's disease: a pilot study. Psychopharmacology 1988, 95, 171-175.
9. Sahakian, B.; Jones, G.; Levy, R.; Gray, J.; Warburten, D. The effects of nicotine on attention, information processing, and short-term memory in patients with dementia of the Alzheimer type. Psychiatry 1989, 154, 797-800.
10. Newhouse, P. A.; Potter, A.; Levin, E. D. Nicotinic system involvement in Alzheimer's and Parkinson's diseases. Implications for therapeutics. Drug Aging 1997, 11, 206-228.
11. Fagerstrom, K. O.; Pomerlau, O.; Giordani, B.; Stelson, F. Nicotine may relieve symptoms of Parkinson's disease. Psychopharmacology 1994, 116, 117-119.
12. Prasad, C.; Ikegami, H.; Shimizu, I.; Onaivi, E. S. Chronic nicotine intake decelerates aging of nigrostriatal dopaminergic neurons. Life Sci. 1994, 54, 1169-1184.
13. Sanberg, P. R.; Silver, A. A.; Shytle, R. D.; Philipp, M. K.; Cahill, D. W.; Fogelson, H. M.; McConville, B. Nicotine for the treatment of Tourette's syndrome. J. Pharmacol Ther. 1997, 74, 21-25.
14. Levin, E. D.; Couriers, C. K.; Sparrow, E.; Hinton, S. C.; Erhardt, D.; Meck, W. H.; Rose, J. E.; March, J. Nicotine effects on adults with attention-deficit/hyperactivity disorder. Psychopharmacology 1996, 123, 55-63.
15. Salin-Pascual, R. J.; Rosas, M.; Jimenez-Genchi, A.; Rivera-Meza, B. L.; Delgado-Parra, V. Antidepressant effect of transdermal nicotine patches in non-smoking patients with major depression. J. Clin. Psychiatry 1996, 57, 387-389.
16. Catka, T. E.; Leete, E. Synthesis of a bridged nicotine: 1,2,3,5,6,-. 10b-hexahydropyrido[2,3-g]indolizine. J. Org. Chem. 1978, 43, 2125-2127.
17. Chavdarian, C. G.; Seeman, J. I.; Wooten, J. B. Bridged nicotines. Synthesis of cis-2,3,3a,4,5,9b-hexahydro-1-methyl-1H-pyrrolo-[2,3-f]quinoline. J. Org. Chem. 1983, 48, 492-494.
18. Kanne, D. B.; Ashworth, D. J.; Cheng, M. T.; Mutter, L. C.; Abood, L. G. Synthesis of the first highly potent bridged nicotinoid. 9-Azabicyclo[4.2.1] nona[2,3-c]pyridine (pyrido[3,4-b]-homotropane). J. Am. Chem. Soc. 1986, 108, 7864-7865.
19. Kanne, D. B.; Abood, L. G. Synthesis and biological characterization of pyridohomotropanes. Structure-activity relationships of conformationally restricted nicotinoids J. Med. Chem. 1988, 31, 506-509.
20. Glassco, W.; Suchocki, J.; George, C.; Martin, B. R.; May, E. L. Synthesis, optical resolution, absolute configuration, and preliminary pharmacology of (+)- and (-)-cis-2,3,3a,4,5,9b-hexahydro-1-methyl-1H-pyrrolo[3, 2-h]isoquinoline, a structural analog of nicotine. J. Med. Chem. 1993, 36, 3381-3385.
21. Damaj, M. I.; Glassco, W.; Dukat, M.; May, E. L.; Glennon, R. A.; Martin, B. R. Pharmacology of novel nicotinic analogs. Drug Dev. Res. 1988, 38, 177-187.
22. Szczepanski, S. W.; Anouna, K. G. Synthesis of semi-rigid analogs of anabasine. Tetrahedron Lett. 1996, 37, 8841-8844.
23. Vernier, J.-M.; Holsenback, H.; Cosford, N. D. P.; Whitten, J. P.; Menzaghi, F.; Reid, R.; Rao, T. S.; Scaan, A. I.; Lloyd, G. K; Suto, C. M.; Chavez-Noriega, L. E.; Washburn, M. S.; Urrutia, A.; McDonald, I. A. Conformationally restricted analogues of nicotine and anabasine. Bioorg. Med. Chem. Lett. 1998, 8, 2173-2178.
24. Xu, Y.-z.; Choi, J.; Calaza, M.; Turner, S.; Rapoport, H. Conformationally constrained nicotines. 1-Pyridinyl-7-azabicyclo[2.2.1]-heptane and 1-pyridinyl-8-azabicyclo[3.2.1]octane analogues. J. Org. Chem. 1999, 64, 4069-4078.
25. Turner, S. C.; Zhai, H.; Rapoport, H. Enantiospecific synthesis of annulated nicotine analogues from D- and L-glutamic acid. Pyridotropanes. J. Org. Chem. 2000, 65, 861-870.
26. Lindström, S.; Ripa, L.; Hallberg, A. Synthesis of two conformationally constrained analogues of the minor tobacco alkaloid anabasine. Org. Lett. 2000, 2, 2291-2293.
27. Xu, R.; Dwoskin, L. P.; Grinevich, V.; Sumithran, S. P.; Crooks, P. A. Neuronal nicotinic acetylcholine receptor binding affinities of boron-containing nicotine analogues. Bioorg. Med. Chem. Lett. 2001, 11, 1245-1248.
28. Xu, R.; Dwoskin, L. P.; Grinevich, V.; Sumithran, S. P.; Crooks, P. A. Synthesis and evaluation of conformationally restricted pyridino N-alkylated nicotine analogs as nicotinic acetylcholine receptor antagonists. Drug Dev. Res. 2002, 55, 173-186.
29. Ullrich, T.; Krich, S.; Binder, D.; Mereiter, K.; Anderson, D. J.; Meyer, M. D.; Pyerin, M. Conformationally Constrained Nicotines: Polycyclic, Bridged, and Spiro-Annulated Analogues as Novel Ligands for the Nicotinic Acetylcholine Receptor. J. Med. Chem. 2002, 45, 4047-4054.
30. Zhai, H.; Liu, P.; Luo, S.; Fang, F.; Zhao, M. A facile synthesis of cis-1-methyl-1,2,3,3a,4,8b-hexahydropyrrolo[3,2-f]pyrindine, an annulated nicotine analog. Org. Lett. 2002, 4, 4385-4386.
31. Meijler, M. M.; Matsushita, M.; Altobell, L. J., III; Wirsching, P.; Janda, K. D. A new strategy for improved nicotine vaccines using conformationally constrained haptens. J. Am. Chem. Soc. 2003, 125, 7164-7165.
32. Elmore, D. E.; Dougherty, D. A. A computational study of nicotine conformations in the gas phase and in water. J. Org. Chem. 2000, 65, 742-747.
33. Sarkar, T. K.; Basak, S.; Ghosh, S. K. A novel approach to conformationally restricted analogues of nicotine and anabasine by an intramolecular Hamaguchi-Ibata reaction. Tetrahedron Lett. 2000, 41, 759-762.
34. Sarkar, T. K.; Basak, S.; Slanina, Z.; Chow, T. J. Studies on intramolecular Diels-Alder reactions of furo[3,4-c]pyridines in the synthesis of conformationally restricted analogues of nicotine and anabasine. J. Org. Chem. 2003, 68, 4206-4214.
35. For reviews, see: Chou, T.-S. Heteroaromatic ortho-Quinodimethanes. Rev. Heteroat. Chem. 1993, 8, 65-104.
36. For reviews, see: Collier, S. J.; Storr, R. C. In Progress in Heterocyclic Chemistry: Gribble, W. W., Gilchrist, L., Eds.; Pergamon: New York, 1998; Vol. 10, p 25.
37. For reviews, see: Segura, J. L.; Martin, N. o-Quinodimethanes: Efficient Intermediates in Organic Synthesis. Chem. Rev. 1999, 99, 3199-3246.
38. Ito, Y.; Nakatsuka, M.; Saegusa, T. Syntheses of polycyclic ring systems based on the new generation of o-quinodimethanes. J. Am. Chem. Soc. 1982, 104, 7609-7622.
39. Carly, P. R.; Compernolle, F.; Hoornaert, G. J. Functionalized o-bis(chloromethyl)pyridines as precursors for pyridine o-quinodimethane analogs and their [4+2] cycloadducts. Tetrahedron Lett. 1995, 36, 2113-2116.
40. Carly, P. R.; Cappelle, S. L.; Compernolle, F.; Hoornaert, G. J. Diels-Alder reactions of pyridine o-quinodimethane analogs generated from functionalized o-bis(chloromethyl)pyridines. Tetrahedron 1996, 52, 11889-11904.
41. Horikawa, M.; Hashimoto, K.; Shirahama, H. Efficient synthesis of acromelic acids B and E, which are potent neuroexcitatory amino acids. Tetrahedron Lett. 1993, 34, 331-334.
42. Cappelle, S. L.; Vogels, I. A.; van Meervelt, L.; Compernolle, F.; Hoornaert, G. J. Functionalized pyridine sulfolenes as precursors to pyridine o-quinodimethane derivatives and their [4+2] cycloadducts. Tetrahedron Lett. 2001, 42, 3759-3762.
43. Carly, P. R.; Govaerts, T. C.; Cappelle, S. L.; Compernolle, F.; Hoornaert, G. J. 1,3-Dihydro-2,2-dioxothieno[3,4-c]pyridines as precursors for pyridine o-quinodimethane systems. Tetrahedron 2001, 57, 4203-4212.
44. Sarkar, T. K.; Ghosh, S. K.; Moorthy, J. N.; Fang, J.-M.; Nandy, S. K.; Sathyamurthy, N.; Chakraborty, D. Photochromism and photoreactivity of 2,6-dichloro-4-methyl-3-pyridinecarboxaldehyde in the solid state. Tetrahedron Lett. 2000, 41, 6909-6913.
45. Bergman, J.; Carlsson, R. Synthesis of the indole alkaloid ellipticine. Tetrahedron Lett. 1977, 4663-4666.
46. Bergman, J.; Carlsson, R. Conversion of diindolylmethanes to 3-vinylindoles. A simple synthesis of the indole alkaloid olivacine. Tetrahedron Lett. 1978, 4055-4058.
47. Magnus, P.; Gallagher, T.; Brown, P.; Pappalardo, P. The indole-2,3-quinodimethane strategy for the synthesis of indole alkaloids. Acc. Chem. Res. 1984, 17, 35-41.
48. Sarkar, T. K.; Ghosh, S. K.; Chow, T. J. Synthesis and Reactions of a Stable o-Quinoid 10-π-Electron System, Furo[3,4-c]pyridine. J. Org. Chem. 2000, 65, 3111-3115.
49. Gallagher, T.; Magnus, P. New methods for alkaloid synthesis: Generation of indole-2,3-diquinomethanes as a route to indole alkaloids. Tetrahedron 1981, 37, 3889-3897.
50. Joule, J. A.; Mills, K. Heterocyclic Chemistry; Blackwell Science: Oxford, 2000; p 3.
51. Leusink, F. R.; ten Have, R.; van den Berg, K. J.; van Leusen, A. M. Generation of 2,3-dimethylene-2,3-dihydropyrrole derivatives; intermediates in intra- and inter-molecular Diels-Alder reactions. J. Chem. Soc., Chem. Commun. 1992, 1401-1402.
52. Cardwell, K.; Hewitt, B.; Ladlow, M.; Magnus, P. Methods for indole alkaloid synthesis. A study of the compatibility of the indole-2,3- quinodimethane strategy for the synthesis of 16-methoxy-substituted aspidosperma-type alkaloids. Synthesis of (+)- and (-)-16-methoxytabersonine. J. Am. Chem. Soc. 1988, 110, 2242-2248.
53. Sarkar, T. K.; Basak, S.; Panda, N. A Pummerer-based generation and trapping of furo[3,4-c]pyridines: an approach to nitrogen containing heterocyclic analogues of 1-arylnaphthalene lignans. Tetrahedron Lett. 2002, 43, 1341-1344.
54. Sarkar, T. K.; Panda, N.; Basak, S. A Sequential Pummerer-Diels-Alder Route for the Generation and Trapping of Furo-[3,4-c]pyridines: Synthesis of Heterocyclic Analogues of 1-Arylnaphthalene Lignans. J. Org. Chem. 2003, 68, 6919-6927.
55. Unpublished X-ray crystallographic work with Prof. H.-K. Fun (Malaysia).
56. Brejc, K.; Van Dijk, W. J.; Klaassen, R. V.; Schuurmans, M.; Van Der, O. J.; Smit, A. B.; Sixma, T. K. Crystal structure of an Ach-binding protein reveals the ligand-binding domain of nicotinic receptors. Nature 2001, 411, 269-276.
57. Costa, V.; Nistri, A.; Cavalli, A.; Carloni, P. A structural model of agonist binding to the α3β4 neuronal nicotinic receptor. Br. J. Pharmacol. 2003, 140, 921-931.
58. Moaddel, R.; Jozwiak, K.; Yamaguchi, R.; Cobello, C.; Whittington, K.; Sarkar, T. K.; Basak, S.; Wainer, I. W. On-line screening of conformationally constrained nicotines and anabasines for agonist activity at the α3β4- and α4β2-nicotinic acetylcholine receptors using immobilized receptor-based liquid chromatographic stationary phases. J. Chromatogr., B 2004, 813, 235-240.
59. Dougherty, D. A. Cation-pi interactions in chemistry and biology: A new view of benzene, Phe, Tyr and Trp. Science 1996, 271, 163-168.
60. Crallivan, J. P.; Dougherty, D. A. Cation-π interactions in structural biology. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 9459-9464.
61. Schmitt, J. D.; Sharpless, C. G. V.; Caldwell, W. S. Molecular recognition in nicotinic acetylcholine receptors: The importance of π-cation interactions. J. Med. Chem. 1909, 42, 3066-3074.
62. Latli, B.; D'Amour, K.; Casida, J. E. Novel and potent 6-chloro-3-pyridinyl ligands for the α4β2 neuronal nicotinic acetylcholine receptor. J. Med. Chem. 1999, 42, 2227-2234.
63. Sharples, C. G. V.; Karig, G.; Simpson, G. L.; Spencer, J. A.; Wright, E.; Millar, N. S.; Wonnacott, S.; Gallagher, T. Synthesis and pharmacological characterization of novel analogues of the nicotinic acetylcholine receptor agonist (±)-UB-165. J. Med. Chem. 2002, 45, 3235-3245.
64. Nicolotti, O.; Pellegrini-Callace, M.; Altomare, C.; Carotti, A.; Carrieri, A.; Sanz, F. Ligands of neuronal nicotinic acetylcholine receptor (nAChR): Inferences from the Hansch and 3D quantitative structure activity relationship (QSAR) models. Curr. Med. Chem. 2002, 9, 1-29.
65. 3 nicotinic acetylcholine receptor. J. Med. Chem. 2003, 46, 2031-2048.
66. Hayashi, M.; Unno, T.; Takahashi, M.; Ogasawara, K. A new enantioselective route to the Sceletium alkaloids via a cyclopentanone- cyclohexenone transformation. Tetrahedron Lett. 2002, 43, 1461-1464.
67. Jozwiak, K.; Hernandez, S. C.; Kellar, K. J.; Wainer, I. W. Enantioselective interactions of dextromethorphan and levomethorphan with the α3β4 nicotinic acetylcholine receptor: comparison of Chromatographic and functional data. J. Chromatogr., B 2003, 797, 425-431.
68. Xiao, Y.; Smith, R. D.; Caruso, F. S.; Kellar, K. J. Blockade of Rat α3β4 Nicotinic Receptor Function by Methadone, Its Metabolites, and Structural Analogs. J. Pharmacol. Exp. Ther. 2001, 299, 366-371.
69. Prism 4 for Windows, Graph-Pad Software Inc., San Diego, CA.