Solid-phase synthesis and pharmacological evaluation of analogues of PhTX-12-A potent and selective nicotinic acetylcholine receptor antagonist
Research output: Contribution to journal › Journal article › Research › peer-review
Philanthotoxin-12 (PhTX-12) is a novel potent and selective, noncompetitive antagonist of nicotinic acetylcholine receptors (nAChRs). Homologues of PhTX-12 with 7-11 methylene groups between the primary amino group and the aromatic head-group were synthesized using solid-phase methodology. In vitro electrophysiological studies of nAChR demonstrated that decreasing the number of methylene groups from 12 to 11 significantly increased potency. Antagonism by PhTX-11, like that of PhTX-12, was only weakly voltage-dependent. When the methylene spacer was reduced further, antagonism was decreased below that of PhTX-12, and in some cases potentiation of ACh responses by up to 60% was observed.
|Journal||Bioorganic & Medicinal Chemistry Letters|
|Number of pages||4|
|Publication status||Published - 22 Apr 2002|
- Chromatography, High Pressure Liquid, Drug Evaluation, Preclinical, Mass Spectrometry, Nicotinic Antagonists, Patch-Clamp Techniques, Polyamines, Tyrosine