TY - JOUR
T1 - Transition state analogue inhibitors of protozoan nucleoside hydrolases
AU - Furneaux, Richard H.
AU - Schramm, Vern L.
AU - Tyler, Peter C.
N1 - Funding Information:
The authors thank Dr. Robert W. Miles for the unpublished data of Tables 1 and 2 , Dr. Herbert Wong for an excellent NMR service and Professor Robin Ferrier for assisting with the preparation of the manuscript. This work was supported by research grants from the National Institutes of Health, USA, and the Foundation for Research Science and Technology, New Zealand.
PY - 1999/11
Y1 - 1999/11
N2 - Protozoan parasites are unable to synthesize purines de novo and must rely on purine salvage pathways for their requirements. Nucleoside hydrolases, which are not found in mammals, function as key enzymes in purine salvage in protozoa. Inhibition of these enzymes may disrupt purine supply and specific inhibitors are potential therapeutic agents for the control of protozoan infections. A series of 1,4-dideoxy-1,4-imino-D-ribitols bearing C- bonded aromatic substituents at C-1 have been synthesized, following carbanion additions to the imine 2, and tested as potential nucleoside hydrolase inhibitors. Nucleoside analogues 8, 11, 14, 17, 20, 24-26, 28 exhibit K(i) values in the range 0.2-22 μM against two representative isozymes of protozoan nucleoside hydrolases. (C) 1999 Elsevier Science Ltd.
AB - Protozoan parasites are unable to synthesize purines de novo and must rely on purine salvage pathways for their requirements. Nucleoside hydrolases, which are not found in mammals, function as key enzymes in purine salvage in protozoa. Inhibition of these enzymes may disrupt purine supply and specific inhibitors are potential therapeutic agents for the control of protozoan infections. A series of 1,4-dideoxy-1,4-imino-D-ribitols bearing C- bonded aromatic substituents at C-1 have been synthesized, following carbanion additions to the imine 2, and tested as potential nucleoside hydrolase inhibitors. Nucleoside analogues 8, 11, 14, 17, 20, 24-26, 28 exhibit K(i) values in the range 0.2-22 μM against two representative isozymes of protozoan nucleoside hydrolases. (C) 1999 Elsevier Science Ltd.
KW - Antibiotics
KW - Antiparasitics
KW - Enzyme inhibitors
KW - Nucleosides
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U2 - 10.1016/S0968-0896(99)00210-2
DO - 10.1016/S0968-0896(99)00210-2
M3 - Article
C2 - 10632070
AN - SCOPUS:0033490888
SN - 0968-0896
VL - 7
SP - 2599
EP - 2606
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 11
ER -