Referenced in: none

Automatically associated channels: Kir2.3

Title: Synthesis of novel chiral Δ2-isoxazoline derivatives related to ABT-418 and estimation of their affinity at neuronal nicotinic acetylcholine receptor subtypes.

Authors: Clelia Dallanoce, Pietro Magrone, Carlo Matera, Leonardo Lo Presti, Marco De Amici, Loredana Riganti, Francesco Clementi, Cecilia Gotti, Carlo De Micheli

Journal, date & volume: Eur J Med Chem, 2010 Dec , 45, 5594-601

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20932609

Abstract
The enantiopure diastereomeric Δ2-isoxazoline derivatives (2S,5'R)-5a-10a and (2S,5'S)-5b, (2S,5'S)-9b, (2S,5'S)-11b, which are structural analogues of both ABT-418 2 and oxyimino ethers (S)-3 and (Z)-(S)-4, were synthesized through cycloaddition reactions involving nitrile oxides as 1,3-dipoles and (S)-N-Boc-2-vinylpyrrolidine-13 as the dipolarophile. The absolute configuration was unequivocally assigned to target compounds by means of an X-ray analysis. The derivatives under study were assayed at neuronal acetylcholine nicotinic receptors (nAChRs), where they showed a meaningful reduction in affinity at the heteromeric α4β2 subtype when compared to the reference molecules. Conversely, anti (2S,5'S)-5b and syn (2S,5'R)-10a isomers showed an affinity for the α7 nAChRs comparable to that observed for the model compound ABT-418.