Synthesis and Biological Evaluation of Iodinated and Fluorinated 9-(2-Hydroxypropyl) and 9-(2-Hydroxyethoxy)methyl Purine Nucleoside Analogues

The novel fluorinated and iodinated purine derivatives containing 9-(2-hydroxypropyl) (1a−7a and 9a−13a) and 9-(2-hydroxyethoxymethyl) (1b−3b, 5b, and 7b−12c) side chains were synthesized by a multistep synthetic route involving Baltz−Schiemann's fluorination and diazotation/iodination as key reactions. An unequivocal proof for the stereostructure of 5b was obtained by X-ray structure analysis. New compounds were evaluated for their cytostatic activity against murine leukemia (L1210); mammary carcinoma (FM3A); and human T-lymphocytes (Molt4/C8 and CEM), melanoma (HBL), cervical carcinoma (HeLa), colon carcinoma (HT29 and SW620), laryngeal carcinoma (Hep2), and pancreatic carcinoma (MiaPaCa2) as well as diploid fibroblasts (WI38). Of all the compounds, the 2-aminopurin-6-thione derivative 9a showed the most pronounced inhibitory activity against human SW620 cells. The 2-aminopurin-6-thione derivative 9b exhibited the most selective inhibitory activity against human HeLa, Hep2, SW620, and murine L1210 cell ...