2-Substituted 5,6-dimethyl-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidines: New series of highly potent and specific serotonin 5-HT6 receptor antagonists

The effect of the intramolecular C–H⋯O interactions on the conformational preferences of bis-arylsulfones – 5-HT6receptor antagonists and beyond

“…Attempts to replace this functional group with other fragments in most cases decreased the binding affinity to the receptor. 4,[8][9][10][11]30,31 Despite considering the HBA functionality of the sulfonyl group, its full impact on 5-HT 6 R ligand activity is still unclear.…”

“…Sulfones and sulfonamides are the most widely represented classes of the serotonin receptor subtype 6 (5-HT 6 R) ligands [8][9][10][11][12][13] (87.8% (1817) of the total number (2069) of recognized 5-HT 6 R ligands with inhibition constants K i (or IC 50 /2) 14 # 100 nM; ChEMBL database; 15 ver. 23).…”

Fingerprint-based consensus virtual screening towards structurally new 5-HT6R ligands

“…Though several reports have proven that the presence of a basic nitrogen atom enabling formation of the interaction of its protonated form and D3.32 is not indispensable for 5-HT 6 R anchoring [56][57][58][59][60] , the fraction of nonbasic compounds within known 5-HT 6 R ligands is low (~7% within the set of active compounds included in the training set). The majority of 5-HT 6 R ligands keep fitting the standard pharmacophore model, 61,62 which requires the possession of a positive ionizable group.…”

Synthesis and biological evaluation of novel N1-phenylsulphonyl indole derivatives as potent and selective 5-HT6R ligands for the treatment of cognitive disorders

“…During this decade or so, there was a plenty of chemistry developed around different nuclei including the indole-based ones or even much simpler biphenyl sulfones and sulfonamides [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]34 ( Figure 2). Suven has reported several series of 1-sulfonylindoles bearing the amino group at 3 or 4 or 5 position of the central core [31][32][33] .…”