Cyclic urea and thiourea derivatives as inducers of murine erythroleukemia differentiation

A series of derivatives of tetramethylurea, a known inducer of the differentiation of Friend erythroleukemia cells, has been synthesized and tested for its capacity to induce erythroid maturation, as measured by the synthesis of hemoglobin. Cyclic urea and thiourea derivatives consisting of five-, six-, and seven-membered ring systems containing N-alkyl substituents were prepared. Most of these agents were relatively effective inducers od differentiation, with N-alkyl substitution appearing to be essential for maximum response. The most potent agents developed were N,N'-dimethyl cyclic ureas. Exposure to concentrations of 2 to 4 mM of these derivatives resulted in more than 90% of the cell population achieving a differentiated state. Under these conditions, the parent compound, tetramethylurea, was slightly less efficacious, causing differentiation of only 68% of the population at its maximum effective level of 4 mM.