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.
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]
Novel 5-substituted 3-hydroxyphenyl and 3-nitrophenyl ethers of S-prolinol as α4β2-nicotinic acetylcholine receptor ligands
C. BolchiPrimo
;F. BavoSecondo
;L. Fumagalli;F. Fasoli;M. Pallavicini
2016
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.File | Dimensione | Formato | |
---|---|---|---|
1-s2.0-S0960894X1631126X-main.pdf
accesso riservato
Tipologia:
Publisher's version/PDF
Dimensione
716.59 kB
Formato
Adobe PDF
|
716.59 kB | Adobe PDF | Visualizza/Apri Richiedi una copia |
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.