Arylglycine derivatives as potent transient receptor potential melastatin 8 (TRPM8) antagonists.
| Autor: | Zhu B; Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA. bzhu@its.jnj.com, Xia M, Xu X, Ludovici DW, Tennakoon M, Youngman MA, Matthews JM, Dax SL, Colburn RW, Qin N, Hutchinson TL, Lubin ML, Brandt MR, Stone DJ, Flores CM, Macielag MJ |
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| Jazyk: | angličtina |
| Zdroj: | Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2013 Apr 01; Vol. 23 (7), pp. 2234-7. Date of Electronic Publication: 2013 Feb 04. |
| DOI: | 10.1016/j.bmcl.2013.01.062 |
| Abstrakt: | A series of arylglycine-based analogs was synthesized and tested for TRPM8 antagonism in a cell-based functional assay. Following structure-activity relationship studies in vitro, a number of compounds were identified as potent TRPM8 antagonists and were subsequently evaluated in an in vivo pharmacodynamic assay of icilin-induced 'wet-dog' shaking in which compound 12 was fully effective. TRPM8 antagonists of the type described here may be useful in treating pain conditions wherein cold hypersensitivity is a dominant feature. (Copyright © 2013 Elsevier Ltd. All rights reserved.) |
| Databáze: | MEDLINE |
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