Novel 5-substituted 3-hydroxyphenyl and 3-nitrophenyl ethers of S-prolinol as α4β2-nicotinic acetylcholine receptor ligands
Articolo
Data di Pubblicazione:
2016
Citazione:
Novel 5-substituted 3-hydroxyphenyl and 3-nitrophenyl ethers of S-prolinol as α4β2-nicotinic acetylcholine receptor ligands / C. Bolchi, F. Bavo, L. Fumagalli, C. Gotti, F. Fasoli, M. Moretti, M. Pallavicini. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - 26:23(2016 Dec 01), pp. 5613-5617. [10.1016/j.bmcl.2016.10.078]
Abstract:
A series of 3-nitrophenyl and 3-hydroxyphenyl ethers of (S)-N-methylprolinol bearing bulky and lipophilic substituents at phenyl C5 were tested for affinity at α4β2 and α3β4 nAChRs. The two phenyl ethers 5-substituted with 6-hydroxy-1-hexynyl showed high α4β2 affinity and significantly increased α4β2/α3β4 selectivity compared to the respective unsubstituted parent compounds. Within the two series of novel phenyl ethers, we observed parallel shifts in affinity and, furthermore, the increase in α4β2/α3β4 selectivity resulting from the hydroxyalkynyl substitution parallels that reported for the same modification at the 3-pyridyl ether of (S)-N-methylprolinol (A-84543), a well-known potent α4β2 agonist. On the basis of these results, our nitrophenyl and hydroxyphenyl prolinol ethers can be considered bioisosteres of the pyridyl ether A-84543 and lead compounds candidable to analogous optimization processes.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
nAChR; A-84543; Ligand; Affinity; Bioisosterism; 6-Hydroxy-1-hexinyl
Elenco autori:
C. Bolchi, F. Bavo, L. Fumagalli, C. Gotti, F. Fasoli, M. Moretti, M. Pallavicini
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