Synthesis of analogs of forodesine HCl, a human purine nucleoside phosphorylase inhibitor—Part I

Abstract

Forodesine HCl is being investigated as a potential therapeutic target for the control of T-cell proliferation. During our ongoing process development work on forodesine HCl several novel compounds were identified as possible impurities in the process. Herein we present the synthesis of three novel compounds (2-4).

Structural basis for selective inhibition of purine nucleoside phosphorylase from Schistosoma mansoni: Kinetic and structural studies

“…The selectivity observed in this case is not surprising, since deazaguanines are well-known inhibitors of the mammalian PNPs. 1,3,[26][27][28][29][30][31][32][33] On the other hand, the nucleoside analogs (8-10) showed good selectivity towards the parasite enzyme (from about 2 to 6.4-fold). This set of compounds with different activity against the two PNPs, allowed SSRs to be quantitatively described and categorized.…”

Recent Advances in the Preparation of Enantiomerically Pure Hydroxylamines from Nitrones

“…The resulting hydroxylamine was used for the preparation of analogs of forodesine, a human purine nucleoside phosphorylase inhibitor. [63] The total synthesis of (-)-hyacinthacine C 5 and its epimers at C6 and C7 was achieved by means of a nucleophilic addition of a dithiane to a cyclic nitrone followed by a Cope-House cyclization as a key step. [64] Polyhydroxylated pyrrolidines were prepared in quantitative yield and complete diastereofacil selectivity through the addition of the Still's reagent [65] (a carbinyl carbanion) to polyhydroxylated five-membered cyclic nitrones like 46 (Scheme 13).…”