[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.
Wen
X X
XX
Faculty of Pharmacy, Shandong Medical University, Jinan.
Hu
Z Y
ZY
Guo
D S
DS
Wang
H C
HC
Zhao
Y W
YW
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002210:Caprylates / Q000138:chemical synthesis* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D003651:Decanoates / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology; D051379:Mice; D011728:Pyridones / Q000138:chemical synthesis* / Q000494:pharmacology; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D002210:Caprylates; D003651:Decanoates; D011728:Pyridones; D013844:Thiazoles; C082852:N,N'-bis(5-(1-methyl-2-pyridonyl))-1,6-hexamethylenedicarboxamide; C082850:N,N'-bis(2-(2-thiazolinyl))-1,8-octamethylenedicarboxamide