| Autor: |
Holladay, M. W., Wasicak, J. T., Lin, N.-H., He, Y., Ryther, K. B., Bannon, A. W., Buckley, M. J., Kim, D. J. B., Decker, M. W., Anderson, D. J., Campbell, J. E., Kuntzweiler, T. A., Donnelly-Roberts, D. L., Piattoni-Kaplan, M., Briggs, C. A., Williams, M., Arneric, S. P. |
| Zdroj: |
Journal of Medicinal Chemistry; February 12, 1998, Vol. 41 Issue: 4 p407-412, 6p |
| Abstrakt: |
New members of a previously reported series of 3-pyridyl ether compounds are disclosed as novel, potent analgesic agents acting through neuronal nicotinic acetylcholine receptors. Both (R)-2-chloro-5-(2-azetidinylmethoxy)pyridine (ABT-594, 5) and its S-enantiomer (4) show potent analgesic activity in the mouse hot-plate assay following either intraperitoneal (ip) or oral (po) administration, as well as activity in the mouse abdominal constriction (writhing) assay, a model of persistent pain. Compared to the S-enantiomer and to the prototypical potent nicotinic analgesic agent (±)-epibatidine, 5 shows diminished activity in models of peripheral side effects. Structure−activity studies of analogues related to 4 and 5 suggest that the N-unsubstituted azetidine moiety and the 2-chloro substituent on the pyridine ring are important contributors to potent analgesic activity. |
| Databáze: |
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