Antineoplastic cyclolignan derivatives

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

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549433, A61K 3136, C07D31770

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active

058345078

ABSTRACT:
Antineoplastic cyclolignan derivatives are of formula (I): ##STR1## in which Ar is a 3,4,5-trialkoxyphenyl or 4-hydroxy-3,5-dialkoxyphenyl; X is an oxygen, sulphur or nitrogen atom, a methine group .dbd.CH-- or an alkylmethine group .dbd.C(alkyl)--; Y is a hydrogen atom or an alkyl, alkenyl, (poly)haloalkyl, aryl, hydroxy, alkoxy, amino, monoalkylamino, dialkylamino, (poly)haloalkylamino, arylamino, acyl or acetamido group, or the group Y is absent; Z is an alkyl, hydroxyalkyl, acyl, carboxy, alkoxycarbonyl or aryloxycarbonyl group; and the dotted lines indicate one double bond located at position .DELTA..sup.7-8 or .DELTA..sup.8-8'.

REFERENCES:
Hartwell and Schrecker, "The Chemistry of Podophyllum", Progress in the Chemistry of Organic Natural Products, pp. 84-166, 1957.
Terada et al., "Antitumor Agents. I. DNA Topoisomerase II Inhibitory Activity and the Structural Relationship of Podophyllotoxin Derivatives as Antitumor Agents", Chem. Pharm. Bull., 40(10) 2720-2727, 1992.
Thurston et al., "Antitumor Agents. 78. Inhibition of Human DNA Topoisomerase II by Podophyllotoxin and .alpha.-Peltatin Analogues", J. Med. Chem., 29:1547-1550, 1986.
Rai et al, Chemical Abstracts, 105:164568, (1986).
Rai et al., Current Science, (1986), 55(15), 702-6.
Jones et al., J. Chem. Soc., Perkin Transactions 1, 21, 2541-8, (1993).

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