Synthesis and biological evaluation of 2-fluoro-8-azaadenosine and related compounds.
The synthesis of 2-fluoro-8-azaadenosine (6e) and 2-amino-8-azaadenosine (6d) is described. Condensation of 9H-2,6-bis(methylthio)-8-azapurine (4) with 2,3,5-tri-O-acetyl-D-ribofuranosyl chloride (5) produces a mixture of 6a (9-beta-D-ribofuranosyl) and 7a (8-beta-D-ribofuranosyl). Standard functional group manipulation, including a modified Schiemann reaction to introduce the fluorine, allows preparation of 6d and 6e from the major isomer 6a. By a similar series of reactions the minor component 7a was converted to 7d and 7e, with the ribose ring attached at N-8 of the 8-azapurine ring system. Structure proofs utilized UV and 1H and 13C NMR data. Compounds 6b-e,g and 7b-f were evaluated in the H.Ep.-2 cell culture screen, and compounds 6c-e and 7d were evaluated in the P388 mouse leukemia screen. Adenosine deaminase data are also presented for some compounds.
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002294:Carcinoma, Squamous Cell; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007202:Indicators and Reagents; D007822:Laryngeal Neoplasms; D007941:Leukemia P388 / Q000188:drug therapy*; D007942:Leukemia, Experimental / Q000188:drug therapy*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D007202:Indicators and Reagents; C039366:2-fluoro-8-azaadenosine; D000241:Adenosine