ADENOSINE-DEAMINASE INHIBITORS - SYNTHESIS AND BIOLOGICAL EVALUATION OF 2(S)-HYDROXY-3(R)-NONYL)-1H-IMIDAZO[4,5-C]PYRIDINE (3-DEAZA-(-EHNA)AND CERTAIN C1' DERIVATIVES())
Gcb. Harriman et al., ADENOSINE-DEAMINASE INHIBITORS - SYNTHESIS AND BIOLOGICAL EVALUATION OF 2(S)-HYDROXY-3(R)-NONYL)-1H-IMIDAZO[4,5-C]PYRIDINE (3-DEAZA-(-EHNA)AND CERTAIN C1' DERIVATIVES()), Journal of medicinal chemistry, 37(2), 1994, pp. 305-308
The synthesis of the title compound (15) and its 1'-fluoro (14) and 1'
-hydroxy (12) derivatives is described. Key intermediate 10 was obtain
ed by two routes through condensation of 2R,3R)-3-amino-1,2-O-isopropy
lidene-1,2-nonanediol (3) with either 2,4-dichloro- or 4-chloro-3-nitr
opyridine. When assayed as adenosine deaminase inhibitors, 15 was foun
d to be almost twice as active as its racemate. While hydroxylation at
the 1'-position resulted in an 80-fold decrease in activity, the 1'-f
luoro derivative proved to have activity comparable to that of 3-deaza
-(+)-EHNA.