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.
Synthesis of novel chiral Δ2-isoxazoline derivatives related to ABT-418 and estimation of their affinity at neuronal nicotinic acetylcholine receptor subtypes / C.M.L. Dallanoce, P. Magrone, C. Matera, L. Lo Presti, M. De Amici, L. Riganti, F. Clementi, C. Gotti, C. De Micheli. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 45:12(2010 Dec), pp. 5594-5601.
|Titolo:||Synthesis of novel chiral Δ2-isoxazoline derivatives related to ABT-418 and estimation of their affinity at neuronal nicotinic acetylcholine receptor subtypes|
MAGRONE, PIETRO (Secondo)
|Parole Chiave:||neuronal nicotinic acetylcholine receptors ; ABT-418 ; 1,3-Dipolar cycloaddition ; nicotinic ligands ; Binding affinity|
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
|Data di pubblicazione:||dic-2010|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.ejmech.2010.09.009|
|Appare nelle tipologie:||01 - Articolo su periodico|