[Synthesis of N-substituted polymethylene dicarboxamides as inducers of differentiation]

N-Alkyl polymethylene dicarboxamides are known potent inducers of erythroid differentiation in murine erythroleukemia cells. The most active inducer N,N,N',N'-tetramethyl-1, 6-hexane-dicarboxamide has the same effectiveness as HMBA which has entered clinical trials as a differentiating agent. These compounds also have inducing activity in HL-60 human promyelocytic leukemia cells. In this paper, the synthesis of a series of N,N'-bis[2-(2-thiazolinyl)], N,N'-bis[5-(1-methyl-2-pyridonyl)], N,N'-bis[3-(1-phenyl-5-pyrazolonyl)] polymethylene dicarboxamides and 3,3'-(polymethylene dicarbonyl)bis(1-methyl-2-imidazolidine-thiones) is reported. The inducing activities of the compounds were evaluated in vitro with HL-60 human promyelocytic leukemia cell line. Among them, N,N'-bis[2-(2-thiazolinyl)]-1,8-octamethylene- dicarboxamide (I4) and N,N'-bis[5-(1-methyl-2-pyridonyl)]-1,6-hexamethylenedicarboxami de (II3) were shown to be relatively effective inducers of differentiation.