Solid-phase synthesis and pharmacological evaluation of analogues of PhTX-12-A potent and selective nicotinic acetylcholine receptor antagonist
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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.
Originalsprog | Engelsk |
---|---|
Tidsskrift | Bioorganic & Medicinal Chemistry Letters |
Vol/bind | 12 |
Udgave nummer | 8 |
Sider (fra-til) | 1159-1162 |
Antal sider | 4 |
ISSN | 0960-894X |
Status | Udgivet - 22 apr. 2002 |
ID: 45823749