169156-24-5Relevant academic research and scientific papers
Synthesis and evaluation of N-substituted 2-amino-4,5-diarylpyrimidines as selective adenosine A1receptor antagonists
Alachouzos, Georgios,Lenselink, Eelke B.,Mulder-Krieger, Thea,de Vries, Henk,IJzerman, Adriaan P.,Louvel, Julien
, p. 586 - 602 (2016/10/12)
We report the synthesis and biological evaluation of new 2-amino-4,5-diarylpyrimidines as selective antagonists at the adenosine A1receptor. The scaffold they are based upon is a deaza variation of a previously reported collection of 3-amino-5,6-diaryl-1,2,4-triazines, members of which had a subnanomolar affinity but limited selectivity over the A2Asubtype. Initially, similar structure-affinity relationships at the 5-aryl ring were established, and then emphasis was put on increasing selectivity at the hA1AR by introducing substituents on the N2-position, all the while maintaining a nanomolar affinity. Compound 3z, bearing a trans 4-hydroxycyclohexyl substituent, was identified as a potent (Ki(hA1AR) = 7.7 nM) and selective (Ki(hA2AAR) = 1389 nM) antagonist at the human adenosine A1receptor. Computational docking was effected at the A1and A2Asubtypes, rationalizing the effect of the 4-hydroxycyclohexyl substituent on selectivity, in relation with the nature of the substituent on the 5-position of the pyrimidine.
Exalted resonance demands in the substituent effects on the acetolyses of 2-arylethyl trifluoromethanesulfonates destabilized by cn and cf3 groups
Usui, Satoshi,Tsuboya, Shoko,Umezawa, Yukthiro,Hazama, Ken,Okamura, Mutsuo
experimental part, p. 254 - 260 (2009/05/30)
Substituent effects on the acetolysis rates of 2-aryl-l-cyano-l- (trifluoromethyl)ethyl trifluoromethanesulfonates (α-OTf) and 2-aryl-2-cyano-2-(trifluoromethyl)ethyl trifluoromethanesulfonates (ss-OTf) were investigated by using LArSR equation. The obtained p and r+ values were p = -3.28, r+ = 0.98 and p = -3.48,r+ = 0.93 for the acetolysis of α-OTf and ss-OΥi, respectively. The obtained p values are comparable to those for typical aryl-assisted solvolyses, but the r+ values are much larger. The large r+ values suggest that the ester bond cleavages in the deactivated aryl-assisted solvolyses are assisted by the strong participation of the ss-aryl group.
