Autor: |
Frost JM; Neuroscience Research, Abbott Laboratories, Abbott Park, IL 60064, USA. jennifer.frost@abbott.com, Bunnelle WH, Tietje KR, Anderson DJ, Rueter LE, Curzon P, Surowy CS, Ji J, Daanen JF, Kohlhaas KL, Buckley MJ, Henry RF, Dyhring T, Ahring PK, Meyer MD |
Jazyk: |
angličtina |
Zdroj: |
Journal of medicinal chemistry [J Med Chem] 2006 Dec 28; Vol. 49 (26), pp. 7843-53. |
DOI: |
10.1021/jm060846z |
Abstrakt: |
A series of potent neuronal nicotinic acetylcholine receptor (nAChR) ligands based on a 3,8-diazabicyclo[4.2.0]octane core have been synthesized and evaluated for affinity and agonist efficacy at the human high affinity nicotine recognition site (halpha4beta2) and in a rat model of persistent nociceptive pain (formalin model). Numerous analogs in this series exhibit picomolar affinity in radioligand binding assays and nanomolar agonist potency in functional assays, placing them among the most potent nAChR ligands known for the halpha4beta2 receptor. Several of the compounds reported in this study (i.e., 24, 25, 28, 30, 32, and 47) exhibit equivalent or greater affinity for the halpha4beta2 receptor relative to epibatidine, and like epibatidine, many exhibit robust analgesic efficacy in the rat formalin model of persistent pain. |
Databáze: |
MEDLINE |
Externí odkaz: |
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