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.
Harriman
G C
GC
Department of Medicinal Chemistry, University of Rhode Island, Kingston 02881.
Abushanab
E
E
Stoeckler
J D
JD
D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D002417:Cattle; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000201:enzymology
D058892:Adenosine Deaminase Inhibitors; C040554:(2R,3S)-3-(4-Amino-1H-imidazo(4,5-c)pyridin-1-yl)-2-nonanol; D000225:Adenine