Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive properties of 2-exo-2-(2′,3′-disubstituted 5′-pyridinyl)-7-azabicyclo[2.2.1]heptanes: Epibatidine analogues

Journal of Medicinal Chemistry

Volumn 45, Issue 21, 2002, Pages 4755-4761

  Carroll, F Ivy ^a   Lee, Jeffrey R ^a   Navarro, Hernán A ^a   Ma, Wei ^a   Brieaddy, Lawrence E ^a   Abraham, Philip ^a   Damaj, M I ^b   Martin, Billy R ^b  

^a RTI INTERNATIONAL   (United States)

^b VIRGINIA COMMONWEALTH UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 (3' AMINO 2' CHLORO 5' PYRIDINYL) 7 AZABICYCLO[2.2.1]HEPTANE; EPIBATIDINE; NICOTINE; NICOTINIC RECEPTOR; UNCLASSIFIED DRUG;

ANTINOCICEPTION; ARTICLE; BINDING AFFINITY; CORE TEMPERATURE; CORRELATION ANALYSIS; DRUG SYNTHESIS; HOT PLATE TEST; PAIN; PROTON NUCLEAR MAGNETIC RESONANCE; RECEPTOR BINDING; TAIL FLICK TEST;

ANALGESICS, NON-NARCOTIC; ANIMALS; BICYCLO COMPOUNDS, HETEROCYCLIC; CEREBRAL CORTEX; LIGANDS; MALE; NICOTINIC AGONISTS; PAIN MEASUREMENT; PYRIDINES; RADIOLIGAND ASSAY; RATS; RECEPTORS, NICOTINIC; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0037057561     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0202268     Document Type: Article

References (20)

1. 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.
2. Spande, T. F.; Garraffo, H. M.; Edwards, M. W.; Yeh, H. J. C.; Pannell, L.; Daly, J. W. Epibatidine: A novel (chloropyridyl)-azabicycloheptane with potent analgesic activity from an Ecuadoran poison frog. J. Am. Chem. Soc. 1992, 114, 3475-3478.
3. Decker, M. W.; Arneric, S. P. Nicotinic acetylcholine receptor-targeted compounds: A summary of the development pipeline and therapeutic potential. In Neuronal Nicotinic Receptors: Pharmacology and Therapeutic Opportunities; Arneric, S. P., Brioni, J. D., Eds.; Wiley-Liss: New York, 1999; pp 395-411.
4. Glennon, R. A.; Dukat, M. Central nicotinic receptor ligands and pharmacophores. Pharm. Acta Helv. 2000, 74, 103-114.
5. Holladay, M. W.; Cosford, N. D. P.; McDonald, I. A. Natural products as a source of nicotinic acetylcholine receptor modulators and leads for drug discovery. In Neuronal Nicotinic Receptors: Pharmacology and Therapeutic Opportunities; Arneric, S. P., Brioni, J. D., Eds.; Wiley-Liss: New York, 1999; pp 253-270.
6. Lloyd, G. K.; Williams, M. Neuronal nicotinic acetylcholine receptors as novel drug targets. J. Pharmacol. Exp. Ther. 2000, 292, 461-467.
7. Carroll, F. I.; Liang, F.; Navarro, H. A.; Brieaddy, L. E.; Abraham, P.; Damaj, M. I.; Martin, B. R. Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive properties of 2-exo-2-(2′-substituted 5′-pyridinyl)-7-azabicyclo[2.2.1]heptanes. Epibatidine analogues. J. Med. Chem. 2001, 44, 2229-2237.
8. Jovanovic, M. V. Heterocycles 1984, 22, 1195-1210.
9. Kotian, P. L.; Carroll, F. I. Synthesis of (+)- and (-)-epibatidine. Synth. Commun. 1995, 25, 63-71.
10. Liang, F.; Navarro, H. A.; Abraham, P.; Kotian, P.; Ding, Y.-S.; Fowler, J.; Volkow, N.; Kuhar, M. J.; Carroll, F. I. Synthesis and nicotinic acetylcholine receptor binding properties of exo-2-(2′-fluoro-5′-pyridinyl)-7-azabicyclo[2.2.1]heptane: A new positron emission tomography ligand for nicotinic receptors. J. Med. Chem. 1997, 40, 2293-2295.
11. 7 nicotinic acetylcholine receptor. J. Med. Chem. 2000, 43, 142-145.
12. Damaj, M. I.; Glassco, W.; Aceto, M. D.; Martin, B. R. Antinociceptive and pharmacological effects of metanicotine, a selective nicotinic agonist. J. Pharmacol. Exp. Ther. 1999, 291, 390-398.
13. D'Amour, F. E.; Smith, D. L. A method for determining loss of pain sensation. J. Pharmacol. Exp. Ther. 1941, 72, 74-79.
14. Eddy, N. B.; Leimbach, D. Synthetic analgesics: II. Dithienybutenyl- and benzomorphans. J. Pharmacol. Exp. Ther. 1953, 107, 385-939.
15. Atwell, L.; Jacobson, A. E. The search for less harmful analgesics. Lab. Anim. 1978, 7, 42-47.
16. Tallarida, R. J.; Murray, R. B. Manual of Pharmacological Calculations with Computer Programs; Springer-Verlag: New York, 1987.
17. Rao, T. S.; Correa, L. D.; Reid, R. T.; Lloyd, G. K. Evaluation of anti-nociceptive effects of neuronal nicotinic acetylcholine receptor (NAChR) ligands in the rat tail-flick assay. Neuropharmacology 1996, 35, 393-405.
18. Carroll, F. I.; Lee, J. R.; Navarro, H. A.; Brieaddy, L. E.; Abraham, P.; Damaj, M. I.; Martin, B. R. Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive properties of 2-exo-2-(2′-substituted-3′-phenyl- 5′-pyridinyl)-7-azabicyclo-[2.2.1]heptanes. Novel nicotinic antagonist. J. Med. Chem. 2001, 44, 4039-4041.
19. Damaj, M. I.; Welch, S. P.; Martin, B. R. In vivo pharmacological effects of dihydro-β-erythroidine, a nicotinic antagonist in mice. Psychopharmacology 1995, 117, 67-73.
20. 50) of an enzymatic reaction. Biochem. Pharmacol. 1973, 22, 3099-3108.