- 1,4-disubstituted anthracene antitumor agents
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Three different types of 1,4-disubstituted anthracenes were synthesized, and their cytotoxicity in a panel of tumor cells was compared with that of the corresponding 9,10-disubstituted anthracenes. The panel contained human myeloma, melanoma, colon, and lung cancer cells and sensitive and multidrug- resistant murine L1210 leukemia cells. These compounds had [[(dimethylamino)ethyl]amino]methyl, N-[(dimethylamino)ethyl]carbamoyl, and carboxaldehyde (4,5-dihydro-1H-imidazol-2-yl)hydrazone side chains. The 1,4- diamide was more potent across the tumor panel than the corresponding 9,10- isomer, but the 1,4-diamine and the 1,4-hydrazone were less potent than their 9,10-isomers. Although the 1,4-hydrazone was active against P388 leukemia in mice, it was inactive against L1210 leukemia. Within each pair of compounds, the one with greater average potency against tumor cells gave a greater increase in the transition melt temperature of DNA.
- Iyengar, Bhashyam S.,Dorr, Robert T.,Alberts, David S.,Sólyom, Anikó M.,Krutzsch, Mary,Remers, William A.
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- Synthesis, DNA-damaging and cytotoxic properties of novel topoisomerase II-directed bisantrene analogues
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New bisantrene analogues were synthesized, bearing one or two 4,5-dihydro-1H-imidazol-2-yl hydrazone side chains at positions 1,4 or 9 of the anthracene ring system. A 10-aza-bioisostere was also prepared. The position of substituents in structurally isomeric drugs modulates topoisomerase II poisoning and specificity, along with cytotoxicity.
- Zagotto, Giuseppe,Oliva, Ambrogio,Guano, Fulvio,Menta, Ernesto,Capranico, Giovanni,Palumbo, Manlio
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p. 121 - 126
(2007/10/03)
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- Process for the manufacture of 1,4-disubstituted bicyclic or tricyclic compounds and new 1,4-disubstituted bicyclic compounds
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The present invention provides a new process for the manufacture of 1,4-disubstituted bicyclic or tricyclic compounds by reacting a 1,2-bis-cyanomethyl-benzene or 2,3-bis-cyanomethyl-naphthalene with glyoxal in the presence of a base and a solvent as well as new 1,4-disubstituted bicyclic compounds.
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