ADENOSINE-DEAMINASE INHIBITORS - SYNTHESIS AND BIOLOGICAL EVALUATION OF 4-AMINO-1-(2(S)-HYDROXY-3(R)-NONYL)-1H-IMIDAZO[4,5-C]PYRIDINE (3-DEAZA-(+)-EHNA) AND CERTAIN C1' DERIVATIVES

The synthesis of the title compound (15) and its 1'-fluoro (14) and 1'-hydroxy (12) derivatives is described. Key intermediate 10 was obtained by two routes through condensation of (2R,3R)-3-amino-1,2-O-isopropylidene-1,2-nonanediol (3) with either 2,4-dichloro- or 4-chloro-3-nitropyridine. When assayed as adenosine deaminase inhibitors, 15 was found 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'-fluoro derivative proved to have activity comparable to that of 3-deaza-(+)-EHNA.