Adenosine deaminase inhibitors: synthesis and biological evaluation of unsaturated, aromatic, and oxo derivatives of (+)-erythro-9-(2'S-hydroxy-3'R-nonyl)adenine [(+)-EHNA].
The synthesis and biological evaluation of three classes of chain-modified derivatives of (+)-EHNA are described. Among the 5', 6'-unsaturated derivatives, the Z-isomer was the most potent inhibitor of adenosine deaminase (ADA) but 3-fold less active than (+)-EHNA. Several 9-aralkyladenines (ARADs) have been prepared, and their inhibitory activity was determined. A minimum of two carbon atoms separating the aromatic ring from the adenine-bearing carbon (C-3') was found to be essential for ADA activity equal to or slightly greater than that of (+)-EHNA. Finally, replacement of the C-5' carbon with an oxygen resulted in reduced potency.
Pragnacharyulu
P V
PV
Department of Chemistry, University of Rhode Island, Kingston, Rhode Island 02881-0809, USA.
Varkhedkar
V
V
Curtis
M A
MA
Chang
I F
IF
Abushanab
E
E
D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D002417:Cattle; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D007422:Intestines / Q000201:enzymology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D058892:Adenosine Deaminase Inhibitors; D004791:Enzyme Inhibitors; C010192:9-(2-hydroxy-3-nonyl)adenine; D000225:Adenine