In the search for new anticancer drugs, XXI. Spin labeled nitrosoureas.

The spin labeled nitrosoureas 7a-e and 12 were synthesized and evaluated in vivo for their anticancer activities against the murine lymphocytic leukemia P388. Compounds 7a-c, 7e and 12 possessed activities ranging from 31 to 542 percent increase in life span (%ILS), whereas compound 7d was marginal (%ILS = 21). All CD2F1 male mice treated with the most active compounds (7a and 12) at 35 mg/kg for 9 days were alive after 30 days, whereas all mice treated with the clinical drug CCNU (1c) succumbed. Compounds 7a-e and 12 were further evaluated for their antineoplastic activity against lymphoid leukemia L 1210. Compounds 7a and 12 exhibited, on day 60, a %ILS of 713 and 620, respectively. The lipophilicities of compounds 7a-e and 12 were determined using the EPR and UV methods. Compounds 7a and 12 which differ from CCNU and MeCCNU by the replacement of the cyclohexyl and methylcyclohexyl groups with six and five membered nitroxyl radical moieties were more hydrophilic than the clinical drugs.