Synthesis and biological activity of several amino analogs of thymidine

• Published in: Journal of medicinal chemistry Vol. 21; no. 1; pp. 109 - 112
• Main Authors: Lin, Tai-Shun, Prusoff, William H
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.01.1978
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Antiviral Agents - chemical synthesis; Cell Division - drug effects; Cells, Cultured; Leukemia L1210 - pathology; Sarcoma 180 - pathology; Thymidine - analogs & derivatives; Thymidine - chemical synthesis; Thymidine - pharmacology; Virus Replication - drug effects
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00199a020

3',5'-Diamino-3',5'-dideoxythymidine (7) was synthesized via a nine-step synthesis from thymidine in good overall yield. 3'-Amino-3'-deoxythymidine (8) and 5'-amino-5'-deoxythymidine (12) were prepared with a minor modification of the procedure reported by Horwitz and co-workers. Although the 5'-amino analogue 12 had potent antiviral activity relative to the 3'-amino analogue 8, the latter is a potent inhibitor of the replication of both murine sarcoma 180 cells (ED50 = 5 micrometer) and of murine L1210 cells (ED50 = 1 micrometer) in vitro. Most unexpectedly, however, was the finding of complete lack of either antiviral or antineoplastic activity by the 3',5'-diamino analogue 7 which appears to have acquired the undesirable qualities of both the 3'-amino and 5'-amino analogues of thymidine.