Privileged S -Triazines: Structure and Pharmacological Applications

Abstract

This review summarizes recent reports on s-triazine and its respective analogs from the medicinal chemistry angle. Due to its high reactivity and binding characteristic towards various enzymes, s-triazine has attracted attention. This is combined with facile synthesis and interesting pharmacology. The triazine class demonstrates wide biological applications - including antimicrobial, antituberculosis, anticancer, antiviral and antimalarial. In this article the library of s-triazine-based molecular designs has been collated with respective bioactivity. Compounds are further compared with other heterocyclic/nontriazine moieties to correlate the efficiency of privileged s-triazine. We hope this article may assist chemists in their drug design and discovery efforts.

Synthesis, Characterization, and Tautomerism of 1,3-Dimethyl Pyrimidine-2,4,6-Trione s-Triazinyl Hydrazine/Hydrazone Derivatives

“…1,3,5-Triazine or s-triazine belongs to the group of heterocyclic compounds having significant applications within pharmaceuticals, textile, rubber, and plastics industries, and as polymer photostabilizers, herbicides, dyestuffs, optical bleaches, explosives, and surface active agents [1,2]. Several derivatives of s-triazine have exhibited antimicrobial [3], antibacterial [4], antifungal [3], anti-HIV [5], anticancer [6,7], and a wide range of other biological activities [8][9][10].…”

Design, synthesis and characterization of [1,3,4]thiadiazolo- and [1,2,4]oxadiazolo- substituted 2,4-dicyclopropylamino-6-phenoxy-s-triazines

“…It is a temperature controlled and a step wise process. Similarly, reactive synthons derived from it, thiosemicarbazone 15 and amidine 25 derivatives, can be easily transformed into [1,3,4] Initially, the nucleophilic substitution of a chlorine atom of cyanuric chloride (1) at 0-5 o C by p-hydroxybenzaldehyde gave 2, which on further reaction with cyclopropylamine gave 3. Efavirenz 29 containing the cyclopropylamine group is used as an anti-HIV drug, keeping this in view it was thought of interest to incorporate cyclopropylamine group to compound 2 and 6 with the aim to enhance the overall biological potency of the drugs derived from it.…”

“…An efficient synthetic protocol has been developed for the installation of cyclopropylamine, [1,3,4]thiadiazole and [1,2,4]oxadiazole substituents into the 6-phenoxy [1,3,5]triazine nucleus which contributes to the chemistry of heterocyclic compounds available to drug discovery endeavors.…”

“…1,3,5-Triazine is an important heterocycle and has gained much synthetic popularity due to its broad spectrum of biological properties such as antimicrobial, 1 anticancer, 1 antimalarial, 1 antiviral, 1 antimycobacterial, 1 antibacterial, 1 antiprotozoal, 2 antifungal, 3 anti-trypanosomal, 4 VLA-4 integrin antagonists, 5 cytotoxic, 6 herbicidal, 7 anticonvulsant, 8 anti-inflammatory, 8 analgesic, 9 acetylcholinesterase inhibitors, 10 antiasthamatic 11 and dihydrofolate reductase inhibitors. 12 Recent studies, based on the s-triazine scaffold showing anti-tumour 13 and anti-HIV 14 activity have led these to be considered as most promising molecule to be employed as lead structures in the discovery of newer medicinally potent chemotherapeutic agents.…”

“…This treatment option was explored keeping in view that the presence of bioactive pharmacophores on a single template would significantly help in enhancing the overall biological potency of the parent drug molecule. Inspired by the success of the earlier work 27,28 we planned novel structural modifications of the striazine nucleus by incorporating the active pharmacophores cyclopropylamine, [1,3,4]thiadiazole and [1,2,4]oxadiazole as substituents with the hope to obtain compounds endowed with high biologically active profiles via cost-effective and facile synthetic routes [ Figure. 1, structures 5 and 9]. …”