19816-92-3Relevant articles and documents
Novel acetylcholine and carbamoylcholine analogues: Development of a functionally selective α4β2 nicotinic acetylcholine receptor agonist
Hansen, Camilla P.,Jensen, Anders A.,Christensen, Jeppe K.,Balle, Thomas,Liljefors, Tommy,Fr?lund, Bente
scheme or table, p. 7380 - 7395 (2009/12/07)
A series of carbamoylcholine and acetylcholine analogues were synthesized and characterized pharmacologically at neuronal nicotinic acetylcholine receptors (nAChRs). Several of the compounds displayed low nanomolar binding affinities to the α4β2 nAChR and pronounced selectivity for this subtype over α3β4, α4β4, and α7 nAChRs. The high nAChR activity of carbamoylcholine analogue 5d was found to reside in its R-enantiomer, a characteristic most likely true for all other compounds in the series. Interestingly, the pronounced α4β2 selectivities exhibited by some of the compounds in the binding assays translated into functional selectivity. Compound 5a was a fairly potent partial α4β2 nAChR agonist with negligible activities at the α3β4 and α7 subtypes, thus being one of the few truly functionally selective α4β 2 nAChR agonists published to date. Ligand-protein docking experiments using homology models of the amino-terminal domains of α4β2 and α3β4 nAChRs identified residues Val111(β2)/Ile113(β4) , Phe119(β2)/Gln121(β4), and Thr155(α4)/Ser150(α3) as possible key determinants of the α4β2/α 3β4-selectivity displayed by the analogues.
Enamines of 3,3-Dimethylazetidine
Thompson, Hugh W.,Swistok, Joseph
, p. 4907 - 4911 (2007/10/02)
In an improvement over previous procedures, 3,3-dimethylazetidine (3) has been synthesized in 26percent yield from ethyl cyanoacetate.Rates of formation for the enamines of 3 and of pyrrolidine with 2-methylcyclohexanone (1) and 1-tetralone (2) have been studied.The 5- to 10-fold rate increase observed for 3 is attributed to diminished steric hindrance relative to pyrrolidine.Compared to the enamines of pyrrolidine with 1 and 2, those of 3 methylate initially on nitrogen to ggreater degree and are less selective for monomethylation.The enamine formed between 1 and 3 exists at equilibrium as an 83.17 mixture of tri- and tetrasubstituted isomers, in which the less substituted isomer has its vinyl H 1H NMR peak at δ 4.10.These properties are compared to those of other enamines of 1, in which a predictive relationship had previously been suggested.
