Synthesis and antitumor evaluation of 4-ethoxycarbonyl cyclophosphamide analogs

4-Ethoxycarbonyl analogs of cyclophosphamide and its five-membered ring homolog were synthesized utilizing the cyclization method previously described. N,N-Bis(2-chloroethyl)-4-ethoxycarbonyl-1,3,2-oxazaphospholidin-2-amine 2-oxide demonstrated activity against L-1210 lymphoid leukemia whereas N,N-bis(2-chloroethyl)-4-(ethoxycarbonyl)tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide did not. The oxazaphosphorin-2-amine was evaluated against human epidermoid carcinoma of the nasopharynx (cell culture). The results again were negative: ED50 = 2.8 X 10.