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Bis-azaaromatic quaternary ammonium salts as antagonists at nicotinic receptors mediating nicotine-evoked dopamine release: An investigation of binding conformation.

Abstract：

:A series of conformationally restricted bis-azaaromatic quaternary ammonium salts (3 and 4) have been designed and synthesized in order to investigate the possible binding conformations of N,N'-dodecane-1,12-diyl-bis-3-picolinium dibromide (bPiDDB; 2), a compound which potently inhibits neuronal nicotinic acetylcholine receptors (nAChRs) mediating nicotine-evoked dopamine release. The preliminary structure-activity relationships of these new analogues suggest that bPiDDB binds in an extended conformation at the nAChR binding site, and that flexibility of the linker may be important for its high potency in inhibiting nAChRs mediating nicotine-evoked dopamine release.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Zheng G,Zhang Z,Pivavarchyk M,Deaciuc AG,Dwoskin LP,Crooks PA

doi

10.1016/j.bmcl.2007.10.052

subject

Has Abstract

pub_date

2007-12-15 00:00:00

pages

6734-8

issue

24

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(07)01221-8

journal_volume

17

pub_type

杂志文章

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