The Ohio State University

The United States of America As Represented by the Department of Health

Derek Horton

Waldemar A Priebe

Roderick J Sorenson

Richard L Wolgemuth

Gary W Morrow

John S Swenton

Wolfgang Weckerle

Wolfgang F Weckerle

Ernst F Fuchs

Beat Winter

Tak M Cheung

Compounds of the formula (I) and pharmaceutical preparations containing the same are disclosed ##STR1## wherein R.sup.1 is --OOCR.sup.3 or --OOC(CH.sub.2).sub.n COOR.sup.4 ; R.sup.2 is hydrogen, hydroxy or methoxy; one of X and X' is a halogen atom selected from the group consisting of fluorine, chlorine, bromine and iodine and the other is hydrogen; one of Y and Y' is hydrogen and the other is selected from the group consisting of hydrogen, hydroxy and acyloxy; one of Z and Z' is hydrogen and the other is selected from the group consisting of hydrogen, hydroxy and acyloxy; R.sup.3 is an alkyl group containing 1 to 8 carbon atoms; R.sup.4 is a hydrogen atom, a metal atom, or an alkyl group containing 1 to 4 carbon atoms; and n is an integer of 0 to 6. These compounds are active in the inhibition of malignant diseases.

14-Acyloxy-2'-halo-anthracycline anti-cancer antibiotics

14-acyloxy-2'-halo-anthracycline anti-cancer antibiotics

Anthracycline antibiotics represented by the formula (I) ##STR1## wherein R is hydrogen or hydroxyl, one of X and Y is fluorine and the other is hydrogen or both X and Y are fluorine, and S is a 2-halo sugar moiety; pharmaceutical preparations containing the same; and a method for inhibiting the growth of mammalian tumors are disclosed.

1-fluoro, 4-fluoro, and 1,4-difluoro-2'-halo anthracycline antibiotics

Compounds of the formula ##STR1## wherein R.sup.1 is a hydrogen atom or a hydroxyl group; R.sup.2 is a hydrogen atom or a hydroxyl or methoxyl group; X is a fluorine, chlorine, bromine or iodine atom; one of Y and Y' is a hydrogen atom and the other is a hydrogen atom or a hydroxyl or acyloxy group; R.sup.3 and R.sup.4 are each independently a hydrogen atom, an alkyl group, a halo- or phenyl-substituted alkyl group, an acyl group or a halo- or phenyl-substituted acyl group or R.sup.3 and R.sup.4 together form a polymethylene chain having 4 to 6 carbon atoms, are useful as anti-tumor agents, especially for treating leukemia; in particular these compounds exhibit high antileukemic activity against P388 murine leukemia.

3'-Amino-2' halo-anthracycline antibiotics

Compounds of the formula (I), acid addition salts thereof, and pharmaceutical preparations containing the same are disclosed ##STR1## wherein R.sup.1 is hydroxy; one of X and X' is hydrogen and the other is a halogen atom selected from the group consisting of fluorine, chlorine, bromine, and iodine; one of Y and Y' is hydrogen and the other is selected from the group consisting of hydrogen, hydroxy and --OCOR; one of Z and Z' is hydrogen and the other is hydrogen, hydroxy or --OCOR; and R is a lower alkyl group.

4-Demethoxy-3'-desamino-2'-halo-anthracycline and pharmaceutical

The compounds are derived from aglycons which may be daunomycin, desmethoxy daunomycin, adriamycin and carminomycin. A preferred compound is ##STR1## (1) R'=H; R.sup.2 =OMe; X; Y (2) R'=OH; R.sup.2 =OMe; X; Y

2'Halo derivatives of daunomycin, desmethoxy daunomycin, adriamycin and

A series of compounds showing high antileukemic activity against P388 murine leukemia and increased aqueous solubility due to substitution of --OH for the known --NH.sub.2 at the 3' position of the hexopyranose sugar, i.e., daunosamine. These compounds are coupled products of aglycon selected from daunomycinone, desmethoxy daunomycinone, adriamycinone and carminomycinone. These compounds are coupled at the 0-7 position of the aglycon with an .alpha.-L-lyxo hexopyranose sugar, which sugar isomer particularly sustains or potentiates the biological activity of the coupled compound as well as ameliorates the dose related cardiotoxicity of the parent and known compounds set out below: ##STR1##

7-O-(2,6-Dideoxy-.alpha.-L-lyxo-hexopyranosyl)-daunomycinone, desmethoxy

A method for synthesizing daunosamine hydrochloride from methyl .alpha.-D-mannopyranoside. The major features of the preparative route involve the formation of a 2-deoxy-3-keto intermediate, whose oxime is reduced with high stereoselectivity to the D-ribo-3-amino compound, followed by a stereospecific step late in the sequence to introduce the terminal C-methyl group with inversion at C-5, to generate the required L-lyxo stereochemistry. The synthesis procedure affords daunosamine hydrochloride in 40% overall yield, with no chromatographic procedures for isolation being required in any of the steps.

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Columbus, OH, United States of America

Derek Horton