| Autor: |
Boyd, R. E., Press, J. B., Rasmussen, C. R., Raffa, R. B., Codd, E. E., Connelly, C. D., Li, Q. S., Martinez, R. P., Lewis, M. A., Almond, H. R., Reitz, A. B. |
| Zdroj: |
Journal of Medicinal Chemistry; March 2001, Vol. 44 Issue: 6 p863-872, 10p |
| Abstrakt: |
A series of imidazolylmethylthiophenes has been prepared and evaluated as ligands for the α2 adrenoceptor. These compounds were tested in two animal models that are predictive of analgesic activity in humans. The 3-thienyl compounds were generally the most potent, particularly those with substitution in the 4-position. A subset of the most active compounds was further evaluated for adverse cardiovascular effects in the anesthetized rat model. In addition to excellent binding at the α2D adrenoceptor, the 4-bromo analogues 20e and 21e were very active in the rat abdominal irritant test (RAIT) with ED50 doses of 0.38 and 0.31 mg/kg, respectively. We constructed a pharmacophore model based on the biological activity of the present series, dexmedetomidine (1), and conformationally restrained analogues 3 and 4. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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