Title: 5'-(N-aminoacyl)-sulfonamido-5'-deoxyadenosine: Attempts for a stable alternative for aminoacyl-sulfamoyl adenosines as aaRS inhibitors
Authors: Gadakh, Bharat
Smaers, Simon
Rozenski, Jef
Froeyen, Mathy
Van Aerschot, Arthur # ×
Issue Date: Mar-2015
Series Title: European Journal of Medicinal Chemistry vol:93 pages:227-36
Article number: S0223-5234(15)00096-3
Abstract: Synthesis of aminoacyl-sulfamoyl adenosines (aaSAs) and their peptidyl conjugates as aminoacyl tRNA synthetase (aaRS) inhibitors remains problematic due to the low yield of the aminoacylation and the subsequent conjugation reaction causing concomitant formation of a cyclic adenosine derivative. In an effort to reduce this undesirable side reaction, we aimed to prepare the corresponding aminoacyl sulfonamide (aaSoA) analogues as more stable alternatives for aaSA derivatives. Deletion of the 5'-oxygen in aaSA analogues should render the C-5' less electrophilic and therefore improve the stability of the aminoacyl sulfamate analogues. We therefore synthesized six sulfonamides and compared their activity against the respective aaSA analogues. However, except for the aspartyl derivative, the new compounds are not able to inhibit the corresponding aaRS. Possible reasons for this loss of activity are discussed by modeling and comparison of the newly synthesized aaSoA derivatives with their parent aaSA analogues.
ISSN: 0223-5234
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Medicinal Chemistry (Rega Institute)
× corresponding author
# (joint) last author

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