DESIGN AND SYNTHESIS OF NOVEL REVERSIBLE MICHAEL ACCEPTORS

The need to develop new methods to improve organic synthesis is necessary in response to the continued increase in demand for organic chemistry. By identifying novel target molecules for the synthesis of effective drugs, it has been possible to develop inhibitors of cysteine-rich host enzymes involved in virus replication, protein acyl transferases, and kinases. Small electrophilic molecules can react with a nucleophilic amino acid residue of a target protein via the formation of an irreversible or reversible covalent bond. Thus, modulation of the protein allows for the development of small molecule-based electrophiles as covalent drugs. Michael acceptors are the most successful covalent enzyme modulators. In response to the continuing increase in demand for more environmentally friendly approaches to organic synthesis, it is necessary to develop more efficient methods to improve the preparation and purification of organic molecules. In this paper, we describe the preparation of reversible Michael acceptors using novel amide scaffolds that are covalently modified by a cysteine thiol, followed by their purification using an environmentally friendly procedure. We present herein a methodology for the preparation of novel target molecules that may be useful for the drug design and synthesis of more effective compounds in the future. The results of our study are presented as a result of experimental research conducted to prepare novel aldehydes derived from formyl benzoic acid, 3-(methylthio)-1H-1,2,4-triazol-5-amine, and 2-Aminopyrimidine, and their application to the synthesis of potentially bioactive products, including Michael acceptors derived from cyanoacetamide, pyrazole, and methyl cyanoacetate.