The importance of triazole scaffold in the development of anticonvulsant agents

Abstract

Epilepsy is one of the most important neurological disorders with high prevalence worldwide. Many epileptic patients are not completely treated with available drugs and need multiple therapies. Also, many antiepileptic drugs have shown unwanted side effects and drug interactions. Therefore there are continuing interests to find new anticonvulsant drugs. Triazole ring has been found in the structure of many compounds with diverse biological effects. Due to the success of several triazole-containing drugs that entered the pharmaceutical market as CNS-active drugs, this class of heterocyclic compounds has great importance for discovery and development of new anticonvulsant drugs. In this article, we have tried to summarize the latest efforts which have been made in the design and development of triazole-derived anticonvulsant agents.

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

“…The most promising heterocyclic compounds are azoles, [10][11][12][13][14] which are five-membered nitrogen heterocycles. The nitrogen-containing azole skeleton offers the advantage of two nitrogen heteroatoms in the ring, which has an important effect on structural modifications and biological interactions.…”

Design, synthesis, and evaluation of anticonvulsant activities of benzoxazole derivatives containing the 1,2,4‐triazolone moiety

“…GABA type A receptors are valuable for their rich pharmacology as they are targets for a range of therapeutically important drugs, including the benzodiazepines (BZDs), barbiturates, neuroactive steroids, and anesthetics . Triazole is a functionalized fragment in a variety of different compounds in medicinal chemistry and has been reported to exhibit a broad range of biological properties . Since the approval and sales of triazolam and alprazolam (two of BZDs) as anticonvulsants in the 1980s, more and more medicinal chemists paid their attention to design and synthesis of the triazole‐derivatives for their anticonvulsant activity…”

“…[6,7] Triazole is a functionalized fragment in a variety of different compounds in medicinal chemistry and has been reported to exhibit a broad range of biological properties. [8] Since the approval and sales of triazolam and alprazolam (two of BZDs) as anticonvulsants in the 1980s, more and more medicinal chemists paid their attention to design and synthesis of the triazole-derivatives for their anticonvulsant activity. [9] In previous work, the anticonvulsant activity of a series of benzoxazole derivatives containing triazole were reported ( Figure 1; I).…”

Synthesis of Novel Derivatives of 1,2,4‐Triazoles

“…Among a large number of nitrogen heterocycles, which differ in the size of cycles and the number of heteroatoms, triazoles, and in particular, 1,2,4‐triazoles are of certain interest. Compounds of this class are not found in natural sources, but thanks to the vigorous development of the chemistry of triazoles, in recent years numerous methods for the synthesis of new 1,2,4‐triazole derivatives have been developed ‐ the ones combined with various heterocycles,− condensed systems,– and in some cases with the use of microwave radiation.a, Biological research has shown that 1,2,4‐triazoles have a broad spectrum of physiological action: they are antioxidants, insecticides,, inhibitors of p38 MAP kinases, display antimicrobial,, antibacterial,, anticonvulsive,, antitumor,, antifungal, activities, etc.…”