azaguanine and Laryngeal-Neoplasms

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.

Topics: Adenosine; Animals; Antineoplastic Agents; Carcinoma, Squamous Cell; Cell Line; Drug Evaluation, Preclinical; Humans; Indicators and Reagents; Laryngeal Neoplasms; Leukemia P388; Leukemia, Experimental; Magnetic Resonance Spectroscopy; Mice; Spectrophotometry, Ultraviolet; Structure-Activity Relationship

Topics: Adenoviridae; Animals; Autoradiography; Azaguanine; Carcinoma, Squamous Cell; Cell Fusion; Cell Line; Cell Transformation, Neoplastic; Cricetinae; Dactinomycin; Deoxyuridine; Inclusion Bodies, Viral; Laryngeal Neoplasms; Mitomycins; Parainfluenza Virus 1, Human; Phenylalanine; Puromycin; Thiouracil; Thymidine; Tritium; Virus Replication

Topics: Antimetabolites; Azaguanine; Carcinoma; Cell Division; Cell Line; Cell Survival; Cytarabine; DNA Replication; Dose-Response Relationship, Drug; Floxuridine; Fluorouracil; Humans; Hydroxyurea; Laryngeal Neoplasms; Mercaptopurine; Methotrexate; Mitosis; Ribonucleosides; Thioguanine; Time Factors; Tritium