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'-bis2-(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'-bis5- (1-methyl- 2-pyridonyl)-1,6-hexamethylenedicarboxamide (Ⅱ₃) were shown to be relatively effective inducers of differentiation.