New Antiproliferative Agents from a Peptidomimetic Library

It is known that chiral ATP analogue quinazolines show selective Epidermal Growth Factor Receptor Tyrosine Kinase (EGFR TK) inhibitory activity depending on the chirality of the molecule [1]. We have developed new types of chiral quinazoline derivatives by synthesising quinazolyl amino acid derivatives (Figure 1, Library “A”) varying the nature and the configuration of the amino acid residue (-NH-R1) and/or the substituents of the benzene ring (R2). A similar library was developed when we substituted 2-bromoethyl quinazolone derivatives (Figure 1, Library “B”) with different amino acids (-NH-R1). Compounds from Library “B” were condensed with a series of aromatic aldehydes giving Library “C” [2]. The aim of our work was to study how the antiturnour activity is influenced by the nature of the applied amino acids and the substituents of the quinazoline’s benzene ring. Antiproliferative activity of Library “A” compounds have been measured in MTT assay (Figure 2).