1262011-81-3Relevant academic research and scientific papers
Synthesis of novel chiral Δ2-isoxazoline derivatives related to ABT-418 and estimation of their affinity at neuronal nicotinic acetylcholine receptor subtypes
Dallanoce, Clelia,Magrone, Pietro,Matera, Carlo,Lo Presti, Leonardo,De Amici, Marco,Riganti, Loredana,Clementi, Francesco,Gotti, Cecilia,De Micheli, Carlo
experimental part, p. 5594 - 5601 (2011/02/22)
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.
