期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 45, 期 3, 页码 740-743出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm010330+
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Heterocyclic phenazinecarboxamides were prepared by condensation of aminoheterocycles and 2-halo-3-nitrobenzoic acids, followed by reductive ring closure and amidation. They showed similar inhibition of paired cell lines that underexpressed topo II or overexpressed P-glycoprotein, indicating a non topo II mechanism of cytotoxicity and indifference to P-glycoprotein mediated multidrug resistance. Compounds with a fused five-membered heterocyclic ring were generally less potent than the pyrido[4,3-alpha]phenazines. A 4-methoxypyrido[4,3-alpha]phenazine (IC(50)s 2.5-26 nM) gave modest (ca. 5 day) growth delays in H69/P xenografts with oral dosing.
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