A series of water-soluble L-lysyl- and L-alanyl-amide prodrugs of the lipophilic antitumor 2-(4-aminophenyl)benzothiazoles has been synthesized to address formulation and bioavailability issues related to the desired parenteral administration of the chosen clinical candidate. The prodrugs exhibit the required pharmaceutical properties of good water solubility (in weak acid) and stability at ambient temperature and degradation to free base in vivo. The lysyl-amide of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (NSC 710305, 6d) has been selected for phase 1 clinical evaluation.

This paper deals with the group ring of a group of prime power order over the prime field GF(p), where p is the prime dividing the order of the group. It is well known that in the case of the group ring of a group over a field whose characteristic divides the order of the group, the ordinary theory of group characters is no longer valid: recently, Brauer and Nesbitt(1) have investigated the properties of the modular representations in this case, but this general theory yields only little in the special case that we consider here. We investigate the group ring from the point of view of the structure of its radical, and in particular, determine a basis for, and the ranks of, the various powers of the radical in terms of the elements and order of a new series of characteristic subgroups. These subgroups are defined by a certain minimal property which combines the commutator and the pth power structure of the group, and should prove useful in general investigations on the structure of p-groups.

Introduction. In this paper we study the (discrete) group ring Γ of a finitely generated torsion free nilpotent group over a field of characteristic zero. We show that if Δ is the ideal of Γ spanned by all elements of the form G − 1, where G ∈ , thenand the only element belonging to Δw for all w is the zero element (cf. (4.3) below).

Carboxylic acids derived from the amido groups of the antitumor agents mitozolomide and temozolomide have been conjugated to simple amino acids and peptides by carbodiimide coupling. Solid-state peptide synthesis has been applied to link the acids to DNA major groove-binding peptidic motifs known to adopt alpha-helical conformations. Attachment of the acids to pyrrole and imidazole polyamidic lexitropsins gave a series of potential DNA minor groove-binding ligands. In vitro biological evaluation of a limited number of these novel conjugates failed to demonstrate any enhanced growth-inhibitory activity compared to the unconjugated drugs; sites of alkylation at tracts of multiple guanines were also unaffected. Attachment of additional residues at C-8 of the imidazotetrazines did not perturb the chemistry of activation of the bicyclic nucleus, and biological sequelae can be rationalized by invoking the liberation of a common, diffusible, reactive chemical intermediate, the methanediazonium ion.