Oscar L. Acevedo

Rapid communication : Inhibition of adenosine deaminase by azapurine ribonucleosides

We have synthesized several 8-azapurine nucleosides as inhibitors of adenosine deaminase. The presence of a nitrogen on the imidazole ring decreased the Ki value for nebularine by 100-fold but did not lower the Ki value for coformycin. Evaluation of these compounds in a MOLT-4 growth assay revealed that 2-azacoformycin was as effective as 2-deoxycoformycin in potentiating growth inhibition by 2-deoxyadenosine. The azapurine nucleosides merit further study as antitumor agents.

A novel approach towards the synthesis of the 3,4,5-trihydro-1,3-diazepin-5-ol ring structure

A catalytic reduction of the nitrile portion of the trimethylsilyl cyanohydrin 7 to a primary amine has produced an situ annulation to generate the 3,4,5-trihydro-1,3-diazepin-5-ol ring. This ring substructure has demonstrated important biological significant.3

A NOVEL APPROACH TOWARDS THE SYNTHESIS OF THE 3,4,5‐TRIHYDRO‐1,3‐DIAZEPIN‐5‐OL RING STRUCTURE

A catalytic reduction of the nitrile portion of the trimethylsilyl cyanohydrin 7 to a primary amine has produced an in situ annulation to generate the 3,4,5-trihydro-1,3-diazepin5-01 ring. This ring substructure has demonstrated important biological significance.3 Our efforts directed towards the synthesis of potential inhibitors of the enzyme adenosine deaminase have yielded a new and novel method for the formation of a 3,4,5-trihydro-1,3-diazepin-5-01 ring (Figure 1, in brackets) fused to another heterocyclic ring. A bicyclic heterocyclic ring system containing the 3,4,5-trihydro-1,3-diazepin-5-01 structure fused to an imidazole ring is shared by the nucleoside antibiotics 2-deoxycoformycin (l_, pentostatin) and coformycin2 (21, both potent inhibitors of adenosine deaminase.3