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The enantiomers of epiboxidine and of two related analogs: Synthesis and estimation of their binding affinity at α4β2 and α7 neuronal nicotinic acetylcholine receptors
Author(s) -
Dallanoce Clelia,
Matera Carlo,
Amici Marco De,
Rizzi Luca,
Pucci Luca,
Gotti Cecilia,
Clementi Francesco,
Micheli Carlo De
Publication year - 2012
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.22052
Subject(s) - epibatidine , chemistry , enantiomer , nicotinic agonist , acetylcholine receptor , stereochemistry , nicotinic acetylcholine receptor , heptane , receptor , biochemistry , organic chemistry
Epiboxidine hydrochlorides (+)‐ 2 and (−)‐ 2 , which are the structural analogs of the antipodes of epibatidine (±)‐ 1 , as well as the enantiomeric pairs (+)‐ 3 /(−)‐ 3 and (+)‐ 4 /(−)‐ 4 were synthesized and tested for binding affinity at α4β2 and α7 nicotinic acetylcholine receptor (nAChR) subtypes. Final derivatives were prepared through the condensation of racemic N ‐Boc‐7‐azabicyclo[2.2.1]heptane‐2‐one (±)‐ 5 with the resolving agent ( R )‐(+)‐2‐methyl‐2‐propanesulfinamide. The pharmacological analysis carried out on the three new enantiomeric pairs evidenced an overall negligible degree of enantioselectivity at both nAChRs subtypes, a result similar to that reported for both natural and unnatural epibatidine enantiomers at the same investigated receptor subtypes. Chirality 24:543–551, 2012 . © 2012 Wiley Periodicals, Inc.