Synthesis and antitumor activity of 3,4,5-substituted 1,2,4-triazoles

Abstract

Conditions for effective alkylation of new 3,4-substituted-5-mercapto-1,2,4-triazoles with various alkylating agents are established. Several compounds possessing pronounced antitumor activity have been found in experiments using two xenograft tumor models.

Synthesis, Crystal Structure, and Fungicidal Activity of 5‐(4‐cyclopropyl‐5‐((3‐fluorobenzyl)thio)‐4H‐1,2,4‐triazol‐3‐yl)‐4‐methyl‐1,2,3‐thiadiazole

“…For example, aer the plant inducers such as thiadinal [11], BTH [12], was discovered ( Figure 1), 1,2,3-thiadiazoles pesticide has become one of the focus of developing agrochemicals in academia and industries. Furthermore, 1,2,4-triazoles exhibited a diverse range of bioactivities in medicinal and agrochemical �eld, such as fungicidal [13], anti-HCV [14], anticancer [15], antifungal [16], and antimicrobial [17] agents. Some compounds have been developed as commercial fungicides (Figure 2), such as Triadimefon, Triadimenol, Flusilazole, and so on.…”

Synthesis, Transformations, and Study of Some Biological Properties of New 3,4,5-Substituted 1,2,4-Triazoles

“…It seemed interesting to study the effect of the new triazole derivatives on the level of tumor DNA methylation and to find a possible correlation between the ability to inhibit DNA methylation and the antitumor activity. The series of synthesized compounds were also tested for antibacterial activity based on published reports of the antibacterial properties of 1,2,4-triazole derivatives [6,7].Scheme 1 illustrates the syntheses of the 1,2,4-triazoles.The starting compounds were 1,4-substituted thiosemicarbazides that were prepared by reacting 4-chlorophenoxyacetic acid hydrazide with allyl-, phenyl-, benzyl-, 3-bromo-4-methoxybenzyl-, and cyclohexylisothiocyanates in EtOH [3,4]. Alkaline cyclization of thiosemicarbazides I yielded 3,4-substituted 5-thio-1,2,4-triazoles II -VI, which were stable crystalline compounds.…”

“…Halides of certain structures, i.e., aliphatic and unsaturated acid chlorides or bromides or their esters and amides, were selected for alkylation of the 5-thio group of triazoles II -VI. The alkylation was performed using the methods developed previously by us, i.e., refluxing the triazoles with the appropriate halides in EtOH or H 2 O in the presence of a certain amount of KOH [4]. As a result, a series of new 3,4,5-substituted triazoles (VII -XXV) were synthesized as colorless crystalline compounds.…”

“…The previously synthesized analogs with a 4-bromophenyl or 4-bromophenoxymethylene substituent in this position exhibited moderate experimental antitumor activity [4]. It seemed interesting to study the effect of the new triazole derivatives on the level of tumor DNA methylation and to find a possible correlation between the ability to inhibit DNA methylation and the antitumor activity.…”

“…The starting compounds were 1,4-substituted thiosemicarbazides that were prepared by reacting 4-chlorophenoxyacetic acid hydrazide with allyl-, phenyl-, benzyl-, 3-bromo-4-methoxybenzyl-, and cyclohexylisothiocyanates in EtOH [3,4]. Alkaline cyclization of thiosemicarbazides I yielded 3,4-substituted 5-thio-1,2,4-triazoles II -VI, which were stable crystalline compounds.…”