Pingitore, Valeria; Martinez-Bailen, Macarena; Carmona, Ana T.; Meszaros, Zuzana; Kulik, Natalia; Slamova, Kristyna; Kren, Vladimir; Bojarova, Pavla; Robina, Inmaculada; Moreno-Vargas, Antonio J. published the artcile< Discovery of human hexosaminidase inhibitors by in situ screening of a library of mono- and divalent pyrrolidine iminosugars>, SDS of cas: 10602-04-7, the main research area is mol modeling docking pyrrolidine iminosugar preparation hexosaminidase human acetylglucosaminidase; click alkyne azide triazole cycloaddition catalyst preparation thiourea; enzyme active site human lysosomal hexosaminidase inhibitor; human lysosomal hexosaminidase inhibitor combinatorial library pyrrolidine iminosugar synthesis; Click reaction; Glycosidase inhibitors; Hexosaminidases; Iminosugars; In situ screening; Multivalency.
Two libraries of mono- and dimeric pyrrolidine iminosugars were synthesized by CuAAC and (thio)urea-bond-forming reactions from the resp. azido/aminohexylpyrrolidine iminosugar precursors. The resulting monomeric and dimeric compounds were screened for inhibition of β-N-acetylglucosaminidase from Jack beans, the plant ortholog of human lysosomal hexosaminidases. A selection of the best inhibitors of these libraries was then evaluated against human lysosomal β-N-acetylhexosaminidase B (hHexB) and human nucleocytoplasmic β-N-acetylglucosaminidase (hOGA). This evaluation identified a potent (nM) and selective monomeric inhibitor of hOGA compound I that showed a 6770-fold higher affinity for this enzyme than for hHexB. The corresponding dimeric derivative II further remarkably improved the selectivity in the inhibition of hOGA (2.7 x 104 times more selective for hOGA over hHexB) and the inhibition potency (by one order of magnitude). Docking studies were performed to explain the selectivity of inhibition observed in I.
Bioorganic Chemistry published new progress about 1,3-Dipolar cycloaddition reaction. 10602-04-7 belongs to class alcohols-buliding-blocks, and the molecular formula is C9H8O, SDS of cas: 10602-04-7.
Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts