s-Triazine: A Privileged Structure for Drug Discovery and Bioconjugation

Abstract

This review provides an overview of the broad applicability of s-triazine. Our many years working with this intriguing moiety allow us to discuss its wide activity spectrum (inhibition against MAO-A and -B, anticancer/antiproliferative and antimicrobial activity, antibacterial activity against MDR clinical isolates, antileishmanial agent, and use as drug nano delivery system). Most of the compounds addressed in our studies and those performed by other groups contain only N-substitution. Exploiting the concept of orthogonal chemoselectivity, first described by our group, we have successfully incorporated different nucleophiles in different orders into s-triazine core for application in peptides/proteins at a temperature compatible with biological systems.

Synthesis and Antiproliferative Activity of a New Series of Mono- and Bis(dimethylpyrazolyl)-s-triazine Derivatives Targeting EGFR/PI3K/AKT/mTOR Signaling Cascades

“…The widespread importance of the synthesis and modification of anticancer agents has given rise to many numbers of medicinal chemistry programs. In this regard, s -triazine derivatives have attracted attention due to their remarkable activity against a wide range of cancer cells. − Hexalen, also known as Altretamine (Figure , compound I ), which was first approved by the U.S. Food and Drug Administration (U.S. FDA) in 1990, is an example of an antineoplastic drug based on an s -triazine privileged structure, and it is used for the treatment of refractory ovarian cancer . Other examples of commercial drugs based on the s -triazine moiety include Enasidenib (Idhifa) (Figure , compound II ), which is used to treat IDH2-positive acute leukemia and was first approved by the U.S. FDA in 2017, and Gedatolisib (Figure , compound III ), a first-in-class PI3K/mTOR inhibitor used to treat breast cancer .…”

Steric Shielding Effects Induced by Intramolecular C–H···O Hydrogen Bonding: Remote Borylation Directed by Bpin Groups

“…Certainly, Bpin is not the first IMHB acceptor found in molecules. Nitrogen heterocycles have appeared as part of IMHB networks including C–H···N interactions within heteroarenes. − Pyridines, pyrimidines, and triazines are key motifs of biologically active pharmaceuticals, and therefore, their potential use as steric shields via IMHB drew our attention. − In particular, we became interested in osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor, which presents a pyrimidine group attached to an indole skeleton . We subjected osimertinib analogue 12 to CHB conditions (Figure ).…”

Hyperbranched polymer immobilized palladium nanoparticles as an efficient and reusable catalyst for cyanation of aryl halides and reduction of nitroarenes

“…s-Triazine, as a nitrogen-rich heterocyclic ring, is a very useful platform for the construction of structurally different molecules and stepwise substitution reactions [57][58][59]. When designing support for the Pd-catalyst, we decided to use s-triazine (TZ) as the central core and introduce imidazolium (IL) fragments into the side chains using click reaction of azide with terminal triple bond.…”