TY - JOUR
T1 - Investigation of acyclic uridine amide and 5'-amido nucleoside analogues as potential inhibitors of the Plasmodium falciparum dUTPase
AU - Hampton, Shahienaz E.
AU - Schipani, Alessandro
AU - Bosch-Navarrete, Cristina
AU - Recio, Eliseo
AU - Kaiser, Marcel
AU - Kahnberg, Pia
AU - González-Pacanowska, Dolores
AU - Johansson, Nils Gunnar
AU - Gilbert, Ian H.
PY - 2013/9/15
Y1 - 2013/9/15
N2 - Previously we have shown that trityl and diphenyl deoxyuridine derivatives and their acyclic analogues can inhibit Plasmodium falciparum dUTPase (PfdUTPase). We report the synthesis of conformationally restrained amide derivatives as inhibitors PfdUTPase, including both acyclic and cyclic examples. Activity was dependent on the orientation and location of the amide constraining group. In the case of the acyclic series, we were able to obtain amide-constrained analogues which showed similar or greater potency than the unconstrained analogues. Unfortunately these compounds showed lower selectivity in cellular assays.
AB - Previously we have shown that trityl and diphenyl deoxyuridine derivatives and their acyclic analogues can inhibit Plasmodium falciparum dUTPase (PfdUTPase). We report the synthesis of conformationally restrained amide derivatives as inhibitors PfdUTPase, including both acyclic and cyclic examples. Activity was dependent on the orientation and location of the amide constraining group. In the case of the acyclic series, we were able to obtain amide-constrained analogues which showed similar or greater potency than the unconstrained analogues. Unfortunately these compounds showed lower selectivity in cellular assays.
U2 - 10.1016/j.bmc.2013.07.004
DO - 10.1016/j.bmc.2013.07.004
M3 - Article
C2 - 23916149
SN - 0968-0896
VL - 21
SP - 5876
EP - 5885
JO - Bioorganic & Medicinal Chemistry
JF - Bioorganic & Medicinal Chemistry
IS - 18
ER -