840-68-6Relevant academic research and scientific papers
The Triazole Ring as a Privileged Scaffold for Putative Antifungals: Synthesis and Evaluation of a Series of New Analogues
Zoidis, Grigoris,Kritsi, Eftichia,Lecinska, Paulina,Ivanov, Marija,Zoumpoulakis, Panagiotis,Sokovic, Marina,Catto, Marco
, p. 134 - 144 (2020/08/24)
The significant antifungal activity of a series of novel 1,2,4-triazole derivatives against different strains of Candida albicans, Candida krusei and Aspergillus fumigatus, compared to the commercial fungicides ketoconazole and itraconazole, is reported. Systemic mycosis and invasive fungal infections, whether from immunodeficiency or hospital-acquired infection, have been on an upward trend for several years. The 1,2,4-triazole ring substituted with other aromatic and heteroaromatic systems plays an important role in the field of antifungal drug discovery and development. Thus, an extensive series of 29 triazoles, substituted in different positions with a variety of aromatic rings, has been designed, synthesized, and evaluated for their fungicidal activity. Almost all the agents tested in vitro showed high activity against all examined fungal strains. It is noteworthy that, in the case of A. fumigatus, all the examined compounds achieved equal or higher antifungal activity than ketoconazole, but less activity than itraconazole. Among all the derivatives studied, the dichlorourea analogue and bromo-substituted triazole stand out as the most promising compounds. Quantitative structure-activity relationship (QSAR) models were built for a systematic structure-activity relationship (SAR) profile to explain and potentially explore the potency characteristics of 1,2,4-triazole analogues.
Development of novel liver?X?receptor modulators based on a 1,2,4-triazole scaffold
Goher, Shaimaa S.,Griffett, Kristine,Hegazy, Lamees,Elagawany, Mohamed,Arief, Mohamed M.H.,Avdagic, Amer,Banerjee, Subhashis,Burris, Thomas P.,Elgendy, Bahaa
, p. 449 - 453 (2019/01/04)
Liver X Receptor (LXR) agonists have been reported as a potential treatment for atherosclerosis, Alzheimer's disease and hepatitis C virus (HCV) infection. We have designed and synthesized a series of potent compounds based on a 1,2,4-triazole scaffold as novel LXR modulators. In cell-based cotransfection assays these compounds generally functioned as LXR agonists and we observed compounds with selectivity towards LXRα (7-fold) and LXRβ (7-fold) in terms of potency. Assessment of the effects of selected compounds on LXR target gene expression in HepG2 cells revealed that compounds 6a-b and 8a-b behaved as inverse agonists on FASN expression even though they were agonists in the LXRα and LXRβ cotransfection assays. Interestingly, these compounds had no effect on the expression of SREBP-1c confirming a unique LXR modulator pharmacology. Molecular docking studies and evaluation of ADME properties in-silico show that active compounds possess favorable binding modes and ADME profiles. Thus, these compounds may be useful for in vivo characterization of LXR modulators with unique profiles and determination of their potential clinical utility.
THE PREPARATION OF 3-BENZYL-6-(α-METHYLBENZYL)-AND 3,6-BIS(α-METHYLBENZYL)-s-TETRAZINES BY ALKYLATION OF 3,6-DIBENZYL-s-TERAZINE AND A STUDY OF THEIR REARRANGEMENTS TO IMIDAZO-s-TETRAZINES IN ALKALI
Hunter, Daniel,Neilson, Douglas G.
, p. 1439 - 1446 (2007/10/02)
3,6-Dibenzyl-s-tetrazine (1a) can be alkylated with methyl iodide after treatment with LDA in tetrahydrofuran to give a mixture of 3-benzyl-6-(α-methylbenzyl)- and 3,6-bis(α-methylbenzyl)-s-tetrazines (1c) and (18) separable by chromatography. 3,6-Dibenzyl-s-tetrazine on treatment with potassium hydroxide in benzyl alcohol yields, among other products, 3-benzyl-7-benzyloxy- and 3,7-dibenzyl-6-phenylimidazol-s-tetrazines (8b) and (5a), the 7-benzyloxy group being generated from the solvent but the 7-benzyl group having the parent tetrazine (1a) as its precursor.Similar treatment of 3-benzyl-6-(α-methylbenzyl)-s-tetrazine (1c) but with methanol as solvent yields the related 7-methoxy-3-(α-methylbenzyl)-6-phenylimidazo-s-tetrazine (8c) along with a novel compound assigned the structure of a substituted 1,2,4-triazolopyrazino-s-tetrazine (15). 3,6-Bis(α-methylbenzyl)-s-tetrazine (18) is stable to alkali except when prolonged reaction times are employed when it breaks down to acetophenone, by way of an alkylidene hydrazide intermediate (19).Mechanisms are proposed for each of these reactions.
SUBSTITUENT AND COORDINATION EFFECTS IN SINGLET REACTIONS OF 3-DIAZO-3H-1,2,4-TRIAZOLES WITH SUBSTITUTED BENZENES AND NITRO COMPOUNDS
Glinka, J.,Fiscus, D.,Rao, C. B.,Shechter, H.
, p. 3221 - 3224 (2007/10/02)
3-Diazo-3H-1,2,4-triazoles convert to singlet 3H-1,2,4-triazol-3-ylidenes which (1) effect directed electrophilic substitutions of benzenes and (2) coordinate with benzenoid substituents and nitro compounds to give decomposition or rearrangement products.
Investigations into the Mechanism of the Action of Alkali in Methanol on 3,6-Dibenzyl-s-tetrazines and their 1,4-Dihydro-derivatives: the Role of s-Tetrazines as Hydride Acceptors and an X-Ray Determination of the Structure of 3,6-Bis(4-chlorobenzyl)-1,4-dihydro-s-tetrazine
Hunter, Daniel,Neilson, Douglas G.,Weakley, Timothy J.R.
, p. 1165 - 1170 (2007/10/02)
Evidence is presented for the mechanism of the reaction of potassium hydroxide with 3,6-dibenzyl-s-tetrazines in which some tetrazine molecules act as hydride acceptors to become dihydro-derivatives which, in turn, react with alkali in a competing reaction to form the corresponding 1,3,4-oxadiazoles.The known action of alkali on 3,6-dibenzyl-1,4-dihydro-s-tetrazines to form 1,3,4-oxadiazoles has been shown to require the presence of an oxidising agent and tetrazine can play this role.The structures of the dihydro-derivatives of s-tetrazines have been in doubt, being called 1,2- and/or 1,4-compounds almost at random, but an X-ray determination of the structure of the dihydro-derivative of 3,6-bis(4-chlorobenzyl)-s-tetrazine has shown conclusively that it exists as 1,4-dihydro-compound.
