Synthesis of Covalent Conjugates of Dichloroacetic Acid with Polyfunctional Compounds

Abstract

The development of prodrugs with an ester bond is classical tool to enhance the bioavailability of pharmaceutical compounds including readily ionizable molecules, such as acids or phenols. In this work, we studied the introduction of a dichloroacetic acid fragment into a molecule as an approach to anticancer prodrug development. The metabolically released dichloroacetate will have an additional useful effect by altering the respiratory cycle of cancer cells and promoting their apoptosis. Derivatives of vitamins B1 and C, paracetamol, and salicylic acid, often used in concomitant cancer therapy, were prepared, and the possibility of selective modifi cation of other polyfunctional compounds was studied. The difference in the reactivity of hydroxy groups in tris(hydroxyphenyl)-substituted cis-imidazoline was studied.

Synthetic Design and Biological Evaluation of New p53-MDM2 Interaction Inhibitors Based on Imidazoline Core

“…A fundamentally different synthetic approach, described by us earlier [16,17,20], involved the direct preparation of the cis-imidazoline core from aldehydes by their reaction with ammonia in the appropriate solvents. This method allowed us to obtain diazapentadiene 5 (Figure 1D) followed by disrotatory closure in the presence of a base that led to a synthesis of the imidazoline core 6.…”