Unlocking the Chemotherapeutic Potential of β‐Aminovinyl Ketones and Related Compounds

Abstract

The role of beta-aminovinyl ketones as synthetic intermediates has been well categorised, but recent developments have shown an interesting array of applications and new chemotherapeutic potential, both in the preparation of biologically active heterocycles and as pharmacophores in their own right.Medicinal chemists are accustomed to using the products of Knoevenagel-type condensations as auxiliaries for the synthesis of N-containing heteroaromatic compounds. One such example of these chemical building blocks are beta-aminovinyl ketones-valuable synthetic intermediates that have been used in the preparation of pyridines, pyrimidines, pyrazoles, and many other heterocyclic motifs. This review highlights their recent use in the synthesis of biologically active targets as part of drug discovery programmes and in natural product synthesis. However, it is becoming increasingly evident that the enaminone motif may serve as a therapeutic pharmacophore in its own right. This review highlights the range of biological responses that beta-aminovinyl ketones elicit, including as antitumour, antibacterial, and anticonvulsant agents. Thus, with a broad spectrum of biological properties and as versatile chemical intermediates, it is clear that beta-aminovinyl ketones offer great potential in the search for new chemotherapeutic agents.

Microwave-Assisted Synthesis of a Pyrazolyl Ketone Library for Evaluation as P38 Mapk Inhibitors in Werner Syndrome Cells

“…Fol low i n g ou r m ic row ave -me d i ate d route (FiguRe 2), two benzoylacetonitriles 1A and 1B, the former readily available from methyl 4-methoxybenzoate by reaction with acetonitrile under basic conditions [27], were reacted with N,N´-diphenylformamidine in a microwaveassisted Knoevenagel condensation reaction at future science group 180°C to give the two β-aminovinyl ketone precursors [28] 2A & B in good yield after 20-30 min. Heterocyclocondensation was then effected, also under microwave dielectric heating, by irradiating 2A & B with a range of hydrazines 3A-P in ethanol at 140°C in the presence or absence of Et 3 N (depending upon whether the hydrazine was obtained as the free base or HCl salt) to give a 24-membered pyrazolyl ketone library 4A-X (table 1).…”

Synthesis, characterization, and molecular structure investigation of new tetrahydrobenzo[b]thiophene-based Schiff bases: A combined experimental and theoretical study

“…The presence of thiophene motif, either alone or as a fused ring with other heterocyclic moieties, in a number of biological significant molecules has made it prime target for scientific research. It has been known that certain thiophenes possess important biological properties such as anticancer [24], antimicrobial [25], antioxidant [26], antitubercular [27], anti-inflammatory [28], and anti-HCV [29] activities. Certain thiophenes are known as potential inhibitors of D-amino acid oxidase [30], tyrosine phosphatase 1B [31], TNF-α [32], and carbonic anhydrase [33].…”

Regioselective synthesis and antimicrobial studies of novel bridgehead nitrogen heterocycles containing the thienopyrimidinone skeleton

“…Based on these observations and as part of our ongoing studies in the development of new chemotherapeutic agents [12,13], we embarked upon the synthesis of a series of novel condensed tricyclic derivatives containing a thieno [2,3d]pyrimidin-4-one core fused through N-3 with different heterocyclic fragments with the objective to develop new leads and to improve their efficacy.…”