Synthesis and medicinal chemical characterisation of antiproliferative O,N-functionalised isopulegol derivatives

Abstract

Benzylation of isopulegol furnished O-benzyl-protected isopulegol, which was transformed into aminodiols via epoxidation followed by ring opening of the corresponding epoxides and subsequent hydrogenolysis. On the other hand, (−)-isopulegol was oxidised to a diol, which was then converted into dibenzyl-protected diol derivatives. The products were then transformed into aminotriols by using a similar method. The antiproliferative activity of aminodiol and aminotriol derivatives was examined. In addition, structure–activity relationships were also explored from the aspects of substituent effects and stereochemistry on the aminodiol and aminotriol systems. The drug-likeness of the compounds was assessed by in silico and experimental physicochemical characterisations, completed by kinetic aqueous solubility and in vitro intestinal-specific parallel artificial membrane permeability assay (PAMPA-GI) measurements.