Amides and esters of 2-[N-(hydroxypiperidinoalkyl) and (hydroxypyrrolidinoalkyl) aminosulfonyl]-6-nitrobenzoic acids are disclosed to have activity in increasing the sensitivity of hypoxic tumor cells to therapeutic radiation. Also disclosed are methods of preparing such compounds, pharmaceutical compositions including such compounds and methods of treating patients in need of therapeutic radiation with effective amounts of such compounds.

Halogenated pyrimidine nucleoside derivatives with improved aqueous solubility and methods of enhancing the concentration of drugs in malignant tumors and promoting uniform distribution of the drug throughout the tumor. These basic and hydrophilic ester prodrugs are designed to undergo conversion to the active drug by an intramolecular chemical reaction at practical rates under physiological conditions.

A compound of the formula ##STR1## wherein: R.sub.1 and R.sub.2 are defined as follows: R.sub.1 is hydrogen, an alkyl group, or an alkyl group having one or more hydroxy groups; R.sub.2 is an alkyl group having one or more hydroxy groups, or an alkyl group containing an amino group in which the amino function is substituted with hydrogen or one or two individual alkyl groups same or different, or two alkyl groups which together form a cyclic amine, e.g. piperidine; R.sub.3 is hydrogen or an alkyl group; and R.sub.4 is hydrogen or an alkyl group. The compounds have high radiosensitizing activity and selectivity for hypoxic cells.

This application discloses new substituted 3-nitrobenzensulfonamides which are useful in enhancing the effect of therapeutic radiation. It also discloses pharmaceutical composition of such compounds, and a method of treatment of patients by administering an effective amount of a substituted 3-nitrobenzenesulfonamide to a patient in need of radiation therapy.

A compound of the formula: ##STR1## wherein: n is an integer 2,3,4, or 5; R.sub.1 is hydrogen or an alkyl group; and R.sub.2 and R.sub.3 are defined as follows: R.sub.2 is hydrogen or an alkyl group; R.sub.3 is hydrogen or an alkyl group; or R.sub.2 and R.sub.3 together form a heterocyclic ring, e.g. piperidine, pyrrolidine. The compounds have high radiosensitizing activity, and act as agents toxic to hypoxic cells in the absence of radiation.