Structure-activity studies on 2-methyl-3-(2(S)- pyrrolidinylmethoxy)pyridine (ABT-089): An orally bioavailable 3-pyridyl ether nicotinic acetylcholine receptor ligand with cognition-enhancing properties

Journal of Medicinal Chemistry

Volumn 40, Issue 3, 1997, Pages 385-390

  Lin, Nan Horng ^a   Gunn, David E ^a   Ryther, Keith B ^a   Garvey, David S ^a,b   Donnelly Roberts, Diana L ^a   Decker, Michael W ^a   Brioni, Jorge D ^a   Buckley, Michael J ^a   Rodrigues, A David ^a   Marsh, Kennan G ^a   Anderson, David J ^a   Buccafusco, Jerry J ^c   Prendergast, Mark A ^c   Sullivan, James P ^a   Williams, Michael ^a   Arneric, Stephen P ^a   Holladay, Mark W ^a  

^a ABBOTT LABORATORIES   (United States)

^b NitroMed Research Laboratories   (United States)

^c MEDICAL COLLEGE OF GEORGIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 METHYL 3 (2 PYRROLIDINYLMETHOXY)PYRIDINE; NICOTINE DERIVATIVE; NICOTINIC RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; CHOLINERGIC SYSTEM; COGNITIVE DEFECT; DRUG BIOAVAILABILITY; DRUG CONFORMATION; DRUG EFFECT; DRUG HALF LIFE; DRUG METABOLISM; DRUG RECEPTOR BINDING; MOUSE; NONHUMAN; STRUCTURE ACTIVITY RELATION; TRANQUILIZING ACTIVITY;

ADMINISTRATION, ORAL; ALKALOIDS; ANIMALS; ANTI-ANXIETY AGENTS; AZOCINES; BIOLOGICAL AVAILABILITY; BUNGAROTOXINS; CELL LINE; COGNITION; DOGS; HAPLORHINI; HUMANS; HYPOTHERMIA; ISOXAZOLES; LIGANDS; MAZE LEARNING; MICE; MOLECULAR STRUCTURE; PSYCHOMOTOR PERFORMANCE; PYRROLIDINES; QUINOLIZINES; RECEPTORS, NICOTINIC; RUBIDIUM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0000140208     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm960233u     Document Type: Article

References (23)

1. Holladay, M. W.; Lebold, S. A.; Lin, N.-H. Structure-Activity Relationships of Nicotinic Acetyleholine Receptor Agonists as Potential Treatments for Dementia. Drug Dev. Res. 1995, 35, 191-213.
2. Williams, M.; Sullivan, J. P.; Arneric, S. P. Neuronal Nicotinic Acetyleholine Receptors. Drug News Perspect. 1994, 7, 205-223.
3. McDonald, I. A.; Cosford, N.; Vernier, J.-M. Nicotinic Acetylcholine Receptors: Molecular Biology, Chemistry and Pharmacology. Ann. Rep. Med. Chem. 1995, 30, 41-50.
4. Arneric, S. P.; Anderson, D. J.; Bannon, A. W.; Briggs, C. A.; Buccafusco, J. J.; Brioni, J. D.; Decker, M. W.; Donnelly-Roberts, D.; Gopalakrishnan, M.; Holladay, M. W.; Kyncl, J.; Marsh, K. C.; Pauly, J.; Radek, R. J.; Rodrigues, D.; Sullivan, J. P. Preclinical Pharmacology of ART-418: A Prototypical Cholinergic Channel Activator for the Potential Treatment of Alzheimer's Disease. CNS Drug Rev. 1995, 1, 1-26.
5. 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 Nicotic Acetyleholine Receptors. J. Med. Chem. 1996, 39, 817-825.
6. McBride. P. E. The Health Consequences of Smoking. Med. Clin. N. Am. 1992, 76, 333-353.
7. Carlson, G. M.; Ruddon, R. W.; Hug, C. C., Jr.; Schmiege, S. K.; Bass, P. Analysis of the Site of Nicotine Action on Gastric Antral and Duodenal Contractile Activity. J. Pharmacol. Exp. Ther. 1970, 173, 377-383.
8. Sullivan, J. P.; Donnelly-Roberts, D.; Briggs, C. A.; Gopalakrishnan, M.; Hu, I.; Campbell, J. E.; Anderson, D. J.; Piattoni-Kaplan, M.; Molinari, E.; McKenna, D. G.; Gunn, D. E.; Lin, N.-H.; Ryther, K. B.; He, Y.; Holladay, M. W.; Williams, M.; Arneric, S. P. ABT-089 [2-Methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine dihydrochloride]: A Potent and Selective Cholinergic Channel Modulator with Cytoprotective Properties. J. Pharmacol. Exp. Ther., submitted for publication.
9. 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.
10. Decker, M. W.; Bannon, A. W.; Curzon, P.; Gunther, K. L.; Brioni, J. D.; Holladay, M. W.; Lin, N.-H.; Li, Y.; Daanen, J. F.; Buecafusco, J. F.; Prendergast, M. A.; Jackson, W. J.; Arneric, S. P. Effects of ABT-089, a Novel Cholinergic Channel Modulator, on Cognitive Performance in Rats and Monkeys. J. Pharmacol. Exp. Ther., submitted for publication.
11. Rodrigues, A. D.; Ferrero, J. L.; Amann, M. T.; Rotert, G. A.; Cepa, S. P.; Surber, B. W.; Machinist, J. M.; Tich, N. R.; Sullivan, J. P.; Garvey, D. S.; Fitzgerald, M.; Arneric, S. P. The In Vitro Hepatic Metabolism of ABT-418, A Cholinergic Channel Activator, In Rats, Dogs, Cynomolgus Monkeys, and Humans. Drug Metab. Dispos. 1994, 22, 788-798.
12. Lin, N.-H.; He, Y.; Anderson, D. J.; Wasicak, J. T.; Kasson, R.; Sweeny, D.; Sullivan, J. P. Synthesis and Structure-Activity Relationships of Pyrrolidine-Modified Analogs of the Potent Cholinergic Channel Activator, AST 418. Bioorg. Med. Chem. Lett. 1994, 4, 2389-2394.
13. Evans, D. A.; Takacs, J. M.; Hurst, K. M. Phosphonamide Stabilized Allylic Carbanions. New Homoenolate Anion Equivalents. J. Am. Chem. Soc. 1979, 101, 371-378.
14. Harris, B. D.; Bhat, K. L.; Joullie, M. M. Synthetic Studies of Detoxin Complex II: Synthesis of Detoxin B1 and B3. Heterocycles 1986, 24, 1045-1060.
15. Flores, C. M.; Rogers, S. W.; Pabreza, L. A.; Wolfe, B. B.; Kellar, K. J. A Subtype of Nicotinic Cholinergic Receptor in Rat Brain is Composed of α4 and β2 Subunits and Is Up-regulated by Chronic Nicotine Treatment. Mol. Pharmacol. 1991, 41, 31-37.
16. 3H] Cytisine Binding to Nicotinic Cholinergic Receptors in Brain. Mol. Pharmacol. 1990, 39, 9-12.
17. Gopalakrishnan, M.; Buisson, B.; Touma, E.; Giordano, T.; Campbell, J. E.; Hu, I. C.; Donnelly-Roberts, D.; Arneric, S. P.; Bertrand, D.; Sullivan, J. P. Stable Expression and Pharmacological Properties of the Human α7 Nicotinic Acetylcholine Receptor. Eur. J. Pharmacol. 1995, 290, 237-246.
18. Lukas, R. J. Expression of Ganglia-Type Nicotinic Acetylcholine Receptors and Nicotinic Binding Sites by Cells of the IMR-32 Human Neuroblastoma Clonal Line. J. Pharmacol. Exp. Ther. 1993, 265, 294-302.
19. Sullivan, J. P.; Decker, M. W.; Brioni, J. D.; Donnelly-Roberts, D.; Anderson, D. J.; Bannon, A. W.; Kang, C.-H.; Adams, P.; Piattoni-Kaplan, M.; Buckley, M.; Gopalakrishnan, M.; Williams, M.; Arneric, S. P. (±)-Epibatidine Elicits a Diversity of In Vitro and In Vivo Effects Mediated by Nicotinic Acetylcholine Receptors. J. Pharmacol. Exp. Ther. 1994, 271, 624-631.
20. Brioni, J. D.; O'Neill, A. B.; Kim, D. J. B.; Decker, M. W. Nicotinic Receptor Agonists Exhibit Anxiolytic-like Effects on the Elevated Plus-Maze Test. Eur. J. Pharmacol. 1993, 238, 1-8.
21. Buccafusco, J. J.; Jackson, W. J. Beneficial Effects of Nicotine Administered Prior to a Delayed Matching-to-Sample Task in Young and Aged Monkeys. Neurobiol. Aging 1991, 12, 233-238.
22. 4 adjusted to pH 6.9.
23. Hui, Y. H.; Marsh, K. C. Sensitive Detection of Selected Cholinergic Channel Activators Derivatized with 7-Fluoro-4-Nitrobenzo-2-Oxa-1,3-Diazole. J. Pharm. Biomed. Anal. 1996, 14, in press.