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.
Shewach
D S
DS
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109.
Krawczyk
S H
SH
Acevedo
O L
OL
Townsend
L B
LB
D058892:Adenosine Deaminase Inhibitors; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003839:Deoxyadenosines / Q000494:pharmacology; D007700:Kinetics; D015649:Pentostatin / Q000494:pharmacology; D011684:Purine Nucleosides / Q000494:pharmacology*; D012263:Ribonucleosides / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects
D058892:Adenosine Deaminase Inhibitors; D000970:Antineoplastic Agents; D003839:Deoxyadenosines; D011684:Purine Nucleosides; D012263:Ribonucleosides; D015649:Pentostatin; C005248:nebularine; C058118:2'-deoxyadenosine