Adenosine deaminase inhibitors. Synthesis of deaza analogs of erythro-9-(2-hydroxy-3-nonyl) adenine
- 1 March 1984
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 27 (3) , 274-278
- https://doi.org/10.1021/jm00369a008
Abstract
Structural analogs of erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), in which the adenine moiety of the molecule was modified, were prepared in order to investigate the structural requirement of EHNA as an inhibitor of adenosine deaminase (ADA). Thus, 1- and 3-deaza-EHNA and their 6-deamino analogues were synthesized and evaluated as inhibitors of ADA from calf intestine. Inhibition studies indicated that isosteric substitution of pyrimidine nitrogens by carbons could be tolerated at the enzymatic binding site. In fact, 3-deaza-EHNA had an inhibitory activity comparable to EHNA itself, and 1-deaza-EHNA, though less potent, is a good inhibitor. The 6-amino group gives an important contribution to the enzymatic binding if the N1 nitrogen is also present, conferring on the compound the characteristic of a semitight inhibitor. [ADA inhibitors increase the activity of antitumor agents which are adenosine analogs.].This publication has 6 references indexed in Scilit:
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