Cyclic urea and thiourea derivatives as inducers of murine erythroleukemia differentiation

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Abstract
A series of derivatives of tetramethylurea, a known inducer of the differentiation of Friend erythroleukemia cells, were synthesized and tested for its capacity to induce erythroid maturation as measured by the synthesis of hemoglobin. Cyclic urea and thiourea derivatives consisting of 5-, 6- and 7-membered ring systems containing N-alkyl substituents were prepared. Most of these agents were relatively effective inducers of differentiation, with N-alkyl substitution appearing to be essential for maximum response. The most potent agents develped were N,N''-dimethyl cyclic ureas. Exposure to cocentrations of 2-4 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 85% of the population at its maximum effective level of 4 mM.