Bolchi_2013_Bioorg.Med.Chem.Lett_23_6481

Reference

Title : Design, synthesis and binding affinity of acetylcholine carbamoyl analogues - Bolchi_2013_Bioorg.Med.Chem.Lett_23_6481
Author(s) : Bolchi C , Valoti E , Binda M , Fasoli F , Ferrara R , Fumagalli L , Gotti C , Matucci R , Vistoli G , Pallavicini M
Ref : Bioorganic & Medicinal Chemistry Lett , 23 :6481 , 2013
Abstract :

A series of acetylcholine carbamoyl analogues, cyclised at the carbamate moiety or at the cationic head or at both, were tested for binding affinity at muscarinic and neuronal nicotinic receptors (nAChRs). While no muscarinic affinity was found, submicromolar Ki values, similar to that of carbachol, were measured at alpha4beta2 nAChRs for the enantiomers of 5-dimethylaminomethyl- and 5-trimethylammoniomethyl-2-oxazolidinone, 2 and 2a, and for (S)-N-methylprolinol carbamate (S)-3. Methylation of oxazolidinone nitrogen of 2 and 2a and of N-methylprolinol nitrogen of (S)-3 and, even more, hybridization of cyclic carbamate substructure (oxazolidinone) with cyclic cationic head (N-methylpyrrolidine) markedly lower the nicotinic affinity. Docking results were consistent with SAR analysis highlighting the interaction capabilities of (R)-2a and (S)-3 and the negative effect of intracyclic nitrogen methylation and of double cyclisation.

PubMedSearch : Bolchi_2013_Bioorg.Med.Chem.Lett_23_6481
PubMedID: 24128660

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Citations formats

Bolchi C, Valoti E, Binda M, Fasoli F, Ferrara R, Fumagalli L, Gotti C, Matucci R, Vistoli G, Pallavicini M (2013)
Design, synthesis and binding affinity of acetylcholine carbamoyl analogues
Bioorganic & Medicinal Chemistry Lett 23 :6481

Bolchi C, Valoti E, Binda M, Fasoli F, Ferrara R, Fumagalli L, Gotti C, Matucci R, Vistoli G, Pallavicini M (2013)
Bioorganic & Medicinal Chemistry Lett 23 :6481