Abstract
Abstract Purine nucleoside phosphorylase.(PNP, EC. 2.4.2.1) functions as a salvage enzyme in the purine and is important in the T-cell portion of the immune system As such, PNP is an important therapeutic target for diseases which are T-cell mediated. The biochemical basis for using PNP inhibitors as well as the various classes of inhibitors developed has been recently reviewed. Using X-ray crystallography we have designed and synthesized a series of 7-substituted 2-amino-1,5-dihydroHpyrrolo[3,2-djpyrimidin-4-ones which are potent PNP inhibitors .2-5 The 3-(pyridinylmethyl) derivative 1 (BCX-34, peldesine, IC50 = 0.036 ± 0.003 μM) is in clinical trials for the treatment of cutaneous T-cell Ivqphoma. acute lymphoblastic leukemia and HIV infections.
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