| Autor: |
Scott MK; Drug Discovery Division, The R. W. Johnson Pharmaceutical Institute, Spring House, PA 19447, USA. scottm@prius.jnj.com, Ross TM, Lee DH, Wang HY, Shank RP, Wild KD, Davis CB, Crooke JJ, Potocki AC, Reitz AB |
| Jazyk: |
angličtina |
| Zdroj: |
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2000 Jun; Vol. 8 (6), pp. 1383-91. |
| DOI: |
10.1016/s0968-0896(00)00062-6 |
| Abstrakt: |
The neuropeptide galanin modulates several physiological functions such as cognition, learning, feeding behavior, and depression, probably via the galanin 1 receptor (GAL-R1). Using an HTS assay based on 125I-human galanin binding to the human galanin-1 receptor (hGAL-R1), we discovered a series of 1,4-dithiin and dithiipine-1,1,4,4-tetroxides that exhibited binding affinity IC50's to hGAL-R1 ranging from 190 to 2700 nM. Two of the dithiepin analogues, 7 and 23, behaved pharmacologically as hGAL-R1 antagonists in secondary assays involving adenylate cyclase activity and GTP binding to G-proteins. Analogues 7 and 23 were also active in functional assays involving galanin, reversing the inhibitory effect of galanin on acetylcholine (ACh) release in rat brain hippocampal slices and electrically-stimulated guinea pig ileum twitch. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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