PURINE AND 1-DEAZAPURINE RIBONUCLEOSIDES AND DEOXYRIBONUCLEOSIDES - SYNTHESIS AND BIOLOGICAL-ACTIVITY

A series of 6-(hydroxylamino)purine and -1-deazapurine nucleosides were synthesized and tested for their antitumor and adenosine deaminase inhibitory activity. All the examined molecules displayed an in vitro activity comparable to that of the reference compounds 6-(hydroxylamino)-9-beta-D-ribofuranosylpurine (HAPR) and ara-A, their ID50 ranging from 0.9-mu-M (16) to approximately 100-mu-M (12). The 6-hydroxylamino derivatives of 1-deazapurine 9, 12, and 17 and also the blocked compound 13 are inhibitors of ADA whereas the purine derivatives 4 and 6 and the nitro compounds 11 and 16 are resistant to the enzyme. 7-(Hydroxylamino)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3H-imidazo[4,5-b]pyridine (12), the less cytotoxic but the most active ADA inhibitor in the series (K(i) = 2.7 x 10(-7)), greatly potentiates the antitumor activity of ara-A in vitro.