National Research Development Corporation

British Technology Group Limited

William A Jeffery

Andrew M Creighton

.sup.32 P thiophosphate preparation

Compounds of formula (II) ##STR1## wherein R.sub.1 and R.sub.2 are each separately selected from hydrogen, alkyl, alkenyl and alkynyl groups having up to a maximum of four carbon atoms and being unsubstituted, and alkyl, alkenyl and alkynyl groups having up to a maximum of three carbon atoms and being substituted by one, or in the case of fluoro by one or more, substituents but with the proviso that when R.sub.1 is hydrogen then R.sub.2 is hydrogen or methyl, or R.sub.1 and R.sub.2 together constitute an ethylene bridging group, and R.sub.3 is a group which under physiological conditions undergoes elimination with the formation of a 3,5-dioxopiperazinyl ring, with the further proviso that the compound is in the meso or erythro configuration when each of R.sub.1 and R.sub.2 is the same or different unsubstituted or substituted alkyl, alkenyl or alkynyl group, and salts thereof with a physiologically acceptable inorganic or organic acid, are of value as prodrugs, particularly for effecting cardioprotection.

Pharmaceutical compositions

Compounds of formula (II) ##STR1## wherein R.sub.1 and R.sub.2 are each separately selected from hydrogen, alkyl, alkenyl and alkynyl groups having up to a maximum of four carbon atoms and being unsubstituted, and alkyl, alkenyl and alkynyl groups having up to a maximum of three carbon atoms and being substituted by one, or in the case of fluoro by one or more, substituents but with the proviso that when R.sub.1 is hydrogen then R.sub.2 is hydrogen or methyl, or R.sub.1 and R.sub.2 together constitute an ethylene bridging group, and R.sub.3 is a group which under physiological conditions undergoes elimination with the formation of a 3,5-dioxopiperazinyl ring, with the further proviso that the compound is in the meso or erythro configuration when each of R.sub.1 and R.sub.2 is the same or different unsubstituted or substituted alkyl, alkenyl or alkynyl group, and salts thereof with a physiologically acceptable inorganic or organic acid, are of value as prodrugs, particularly in the therapy of cancers sensitive to the compounds of formula (II) and psoriasis.

Pharmaceutical compositions for treating certain cancers

Compounds of formula (II) ##STR1## wherein R.sub.1 and R.sub.2 are each separately selected from hydrogen, alkyl, alkenyl and alkynyl groups having up to a maximum of four carbon atoms and being unsubstituted, and alkyl, alkenyl and alkynyl groups having up to a maximum of three carbon atoms and being substituted by one, or in the case of fluoro by one or more, substituents but with the proviso that when R.sub.1 is hydrogen then R.sub.2 is hydrogen or methyl, or R.sub.1 and R.sub.2 together constitute an ethylene bridging group, and R.sub.3 is a group which under physiological conditions undergoes elimination with the formation of a 3,5-dioxopiperazinyl ring, with the further proviso that the compound is in the meso or erythro configuration when each of R.sub.1 and R.sub.2 is the same or different unsubstituted or substituted alkyl, alkenyl or alkynyl group, and salts thereof with a physiologically acceptable inorganic or organic acid, are of value as prodrugs, particularly in the therapy of psoriasis.

Pharmaceutical compositions for treating psoriasis

Compounds of the formula (II) ##STR1## wherein R.sub.1 and R.sub.2 are each separately selected from hydrogen, alkyl, alkenyl and alkynyl groups having up to a maximum of four carbon atoms and being unsubstituted, and alkyl, alkenyl and alkynyl groups having up to a maximum of three carbon atoms and being substituted by one, or in the case of fluoro by one or more, substitutents but with the proviso that when R.sub.1 is hydrogen then R.sub.2 is hydrogen or methyl, or R.sub.1 and R.sub.2 together constitute an ethylene bridging group, and R.sub.3 is a group which under physiological conditions undergoes elimination with the formation of a 3,5-dioxopiperazinyl ring, with the further proviso that the compound is in the meso or erythro configuration when each of R.sub.1 and R.sub.2 is the same or different unsubstituted or substituted alkyl, alkenyl or alkynyl group, and salts thereof with a physiologically acceptable inorganic or organic acid, are of value as prodrugs, particularly in the therapy of cancer and psoriasis.

Compounds of formula (II) ##STR1## wherein R.sub.1 and R.sub.2 are each separately selected from hydrogen, alkyl, alkenyl and alkynyl groups having up to a maximum of four carbon atoms and being unsubstituted, and alkyl, alkenyl and alkynyl groups having up to a maximum of three carbon atoms and being substituted by one, or in the case of fluoro by one or more, substitutents but with the proviso that when R.sub.1 is hydrogen then R.sub.2 is hydrogen or methyl, or R.sub.1 and R.sub.2 together constitute an ethylene bridging group, and R.sub.3 is a group which under physiological conditions undergoes elimination with the formation of a 3,5-dioxopiperazinyl ring, with the further proviso that the compound is in the meso or erythro configuration when each of R.sub.1 and R.sub.2 is the same or different unsubstituted or substituted alkyl, alkenyl or alkynyl group, and salts thereof with a physiologically acceptable inorganic or organic acid, are of value as prodrugs, particularly in the therapy of cancer and psoriasis.

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Maldon, United Kingdom

William A Jeffery