Adenosine deaminase inhibitors. Synthesis and biological evaluation of C1' and nor-C1' derivatives of (+)-erythro-9-(2(S)-hydroxy-3(R)-nonyl)adenine.
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The synthesis of various chiral derivatives of (+)-erythro-9-(2-hydroxy-3-nonyl)adenine, (+)-EHNA, from (2S,3R)-3-amino-1,2-O-isopropylidene-1,2-nonanediol by condensation with 5-amino-4,6-dichloropyrimidine is described. The compounds synthesized were C1'- and nor-C1'-(+)-EHNA derivatives. When tested with calf spleen ADA, C1'-OH- and nor-C1'-(+)-EHNA had comparable inhibitory activity that was 1 order of magnitude lower than that of (+)-EHNA. Potency was reduced further in nor-C1' derivatives.