85103-41-9

Upstream product

• 121-98-2 methyl 4-methoxybenzoate 
• 100-07-2 4-methoxy-benzoyl chloride 
• 10364-93-9 1-(4-methoxybenzoyl)-imidazole 
• 94-30-4 ethyl 4-methoxybenzoate 
• 3290-99-1 4-methoxybenzoic acid hydrazide 
• 75-15-0 carbon disulfide 

Downstream Products

• 23766-26-9 5?(4?methoxyphenyl)?1,3,4?oxadiazole?2?thiol 
• 36209-49-1 4-amino-5-(4-methoxyphenyl)-4H-1,2,4-triazole-3-thiol 
• 111828-03-6 [4-Amino-5-(4-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-acetonitrile 
• 111828-09-2 [4-Amino-5-(4-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-acetic acid methyl ester 
• 111828-14-9 [4-Amino-5-(4-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-acetic acid hydrazide 
• 111828-24-1 [4-Amino-5-(4-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-acetic acid [1-phenyl-meth-(E)-ylidene]-hydrazide 
• 111828-19-4 Benzoic acid N'-{2-[4-amino-5-(4-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-acetyl}-hydrazide 
• 111828-25-2 [4-Amino-5-(4-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]-acetic acid [1-(4-nitro-phenyl)-meth-(E)-ylidene]-hydrazide 
• 1195049-77-4 [Cu(II)(N,N-ethylenediamine)2(5-(4-methoxyphenyl)[1,3,4]-oxadiazole-2-thione)2] 
• 1195049-75-2 [Ni(II)(N,N-ethylenediamine)2(5-(4-methoxyphenyl)[1,3,4]-oxadiazole-2-thione)2] 
• 1427501-07-2 6-(furan-3-yl)-3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole 
• 36209-49-1 4-amino-5-(4-methoxyphenyl)-2,3-dihydro-4H-1,2,4-triazole-3-thione 
• 1578155-35-7 N-(4-chlorophenyl)-6-(3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl)-5-methylselenopheno[2,3-d]pyrimidin-4-amine 
• 1578155-47-1 N-(3-chloro-4-fluorophenyl)-6-(3-(4-methoxyphenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl)-5-methylselenopheno[2,3-d]pyrimidin-4-amine 

Relevant academic research and scientific papers

Efficient Synthesis of Fluorinated [1,2,4]Triazolo[3,4-b][1,3,4]thiadiazoles

Abstract: An efficient synthesis of fluorinated [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives has been achievedby cyclocondensation of 5-substituted 4-amino-1,2,4-triazole-3-thiols withfluoro-substituted aromatic acids using phosphoryl chloride as a cyclizingagent. The synthesized compounds were characterized by spectroscopic techniques,including IR, 1H NMR, and mass spectra.

Efficient formation of C–S bond using heterocyclic thiones and arynes

Phenylthio heterocyclic compounds are widely used because of their diverse biological activities and medicinal prospects. Here, a facile method was reported. An arylation of 1,3,4-oxa(thia)diazol-2-thiones reacting with arynes to build C(aryl)-S bonds in the presence of CsF had good yields and excellent selectivity. The reaction was completed in short time without using expensive reagents and catalysts. Present reaction system is an efficient procedure to process phenylthio heterocyclic compounds and reveals a sustainable method and better application prospects in future organic synthesis.

1,2,4-Triazole-conjugated 1,3,4-thiadiazole hybrid scaffolds: A potent ameliorant of carrageenan-induced inflammation by lessening proinflammatory mediators

Inflammation acts as an alarming signal for the progression of various biological complications. Various reports in the literature have revealed that heterocycle-containing synthetic compounds have a restorative capability against acute and chronic inflammatory stages. In the current study, we synthesized a series of 1,2,4-triazole-conjugated 1,3,4-thiadiazole hybrid scaffolds and evaluated their impacts against carrageenan-induced paw edema and proinflammatory markers in Wistar rats. Further, 3D QSAR study (three-dimensional quantitative structure–activity relationships), ADMET (absorption, distribution, metabolism, and excretion) profiling, and docking studies were performed to determine the possible mechanism of the action of the derivatives. The study shows that the most active derivatives, 13f and 13g, have optimal logP, a higher anti-inflammatory activity score, and poor metabolism at various sites of cytochrome P450. The docking studies recommended that the synthesized compounds have a similar affinity as the ligands A307, 63X, and S58 to interact with tumor necrosis factor-α, COX-1, and COX-2. So, these molecules will definitely hold a promise for the future drug development initiative.

Synthesis of [1,2,4]triazolo[4,3-a]quinoxaline-1,3,4-oxadiazole derivatives as potent antiproliferative agents via a hybrid pharmacophore approach

Imiquimod (1-isobutyl-1H-imidazo[4,5-c]quinolin-4-amine) is efficacious in topical therapy for certain types of skin cancers. Structurally similar EAPB0203 (N-methyl-1-(2-phenethyl)imidazo[1,2-a]quinoxalin-4-amine) has been shown higher in vitro potency than imiquimod. Besides, triazole, oxadiazole, and thiadiazole rings are privileged building blocks in drug design. A series of [1,2,4]triazolo[4,3-a]quinoxaline-1,3,4-oxadiazole and [1,2,4]triazolo[4,3-a]quinoxaline-1,3,4-thiadiazole derivatives were therefore synthesized by incorporation of these rings into the structure of EAPB0203 and assessed their antiproliferative effects against various cancer cell lines. The 1,3,4-oxadiazole derivatives demonstrated the superior effectiveness compared to imiquimod and EAPB0203. Our findings highlight the excellent potential of [1,2,4]triazolo[4,3-a]quinoxaline-1,3,4-oxadiazole derivatives as anticancer agents.

Development of triazolothiadiazine derivatives as highly potent tubulin polymerization inhibitors: Structure-activity relationship, in vitro and in vivo study

Based on our prior work, we reported the design, synthesis, and biological evaluation of fifty-two new triazolothiadiazine-based analogues of CA-4 and their preliminary structure-activity relationship. Among synthesized compounds, Iab was found to be the most potent derivative possessing IC50 values ranging from single-to double-digit nanomolar in vitro, and also exhibited excellent selectivity over the normal human embryonic kidney HEK-293 cells (IC50 > 100 μM). Further mechanistic studies revealed that Iab significantly blocked tubulin polymerization and disrupted the intracellular microtubule network of A549 cells. Moreover, Iab induced G2/M cell cycle arrest by regulation of p-cdc2 and cyclin B1 expressions, and caused cell apoptosis through up-regulating cleaved PARP and cleaved caspase-3 expressions, and down-regulating of Bcl-2. Importantly, in vivo, Iab effectively suppressed tumor growth of A549 lung cancers in a xenograft mouse model without obvious signs of toxicity, confirming its potential as a promising candidate for cancer treatment.

Synthesis and antimicrobial activity of piperine analogues containing 1,2,4-triazole ring

A series 1,2,4-triazole piperine analogues (TP1-TP6) were designed and synthesized. The structures were confirmed using 1H NMR and 13C NMR. Antibacterial study was done using Gram-positive (Staphylococcus aureus and Bacillus cereus) and Gram-negative microorganisms (E. coli and Pseudomonas aeruginosa) by disc diffusion method. Compound containing chloro substitution (TP6) showed the highest effect, while compound TP1, TP3, TP4, TP5 showed the moderate activity.

Synthesis and antitumor evaluation of novel fused heterocyclic 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives

In this study, twenty three 3,6-disubstituted 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives were synthesized and their antiproliferative activities in vitro were studied against SMMC-7721, HeLa, A549, and L929 by the CCK-8 assay. The bioassay results demonstrated that all tested compounds 8(a–w) exhibited antiproliferation with different degrees, and some compounds showed better effects than reference drug 5-fluorouracil. Among these screened compounds, compounds 8a, 8d, and 8l displayed significant antitumor activities in inhibiting SMMC-7721cell proliferation with IC50 values of 1.64, 1.74, and 1.61 μM, respectively. Compounds 8d and 8l were manifested highly effective biological activity versus HeLa cells with IC50 values of 2.23 and 2.84 μM, respectively. Compound 8l was found to have the highest antitumor potency against A549 cells with IC50 value of 2.67 μM. Furthermore, all compounds exhibited weaker cytotoxic effects than 5-fluorouracil on normal cell lines L929.

Design, Synthesis, and Antifungal Activities of Novel 1,2,4-Triazole Schiff Base Derivatives

With the aim to find new compounds with high antifungal activity, 21 4-amino-5-substituted-1,2,4-triazole Schiff bases (2a?–?2g, 3a?–?3g, and 4a?–?4g) were designed and synthesized. Their antifungal activities against Pythium solani, Gibberlla nicotiancola, Fusarium oxysporium f. sp. niveum, Gibberlla saubinetii, Alternaria iycopersici, Phytophthora capsici, Physalospora piricola, Cercospora arachidicola hori, and Fusarium oxysporium f. sp. cucumber were tested, parts of the compounds exhibited excellent antifungal activity. This research provides useful information for further study of antifungal agents.

Triazolothiadiazines as a new class of efficient DNA intercalating agents

A new series of N-bridged heterocycles 1,2,4-triazolo[3,4-b][1,3,4]thiadiazine derivatives (6a-e) have been synthesized by the condensation of 4-amino-5-(4-methoxyphenyl)-4H-1,2,4-triazole-3-thiol and various substituted phenacyl bromides in absolute ethanol in high yields. Cyclic voltammetric and molecular docking methods have been used to investigate the interaction of potential binding affinities of 6a-e with DNA. The change in peak potential and peak current is used to probe the mode of interaction, formation constant Kf, free binding energy and irreversible nature of system. The DNA-binding potency of 6a (Kf = 5.00 105 M-1) and 6c (Kf = 4.80 105 M-1) are found to be greater than epirubicin (Kf = 4.1 105 M-1), the clinically used anticancer drug. The positive shift in peak potential revealed the intercalative mode of interactions. The high negative value of ?G signifies the spontaneity and high conformational stability of compound-DNA adduct. A molecular docking study of all the compounds using Auto-Dock 4.2 confirmed additional specificity and insight of the interaction with the DNA. Free energies by theoretical studies had much resemblance and almost completely satisfied the experimental results. From results investigation, it is revealed that the examined compounds exhibit intercalation mode.

Preliminary SAR and biological evaluation of antitubercular triazolothiadiazine derivatives against drug-susceptible and drug-resistant Mtb strains

Following up the SAR study of triazolothiadiazoles for their antitubercular activities targeting Mt SD in our previous study, on the principle of scaffold hopping, the C3 and C6 positions of triazolothiadiazine were examined systematically to define a preliminary structure–activity relationship (SAR) with respect to biological activity. This study herein highlights the potential of two highly potent advanced leads 6c-3, 6g-3 and several other compounds with comparable potencies as promising new candidates for the treatment of TB (6c-3, MIC-H37Rv?=?0.25?μg/mL; MIC-MDRTB?=?2.0?μg/mL; MIC-RDRTB?=?0.25?μg/mL; Mt SD-IC50?=?86.39?μg/mL; and 6g-3, MIC-H37Rv?=?1.0?μg/mL; MIC-MDRTB?=?4.0?μg/mL; MIC-RDRTB?=?2.0?μg/mL; Mt SD-IC50?=?73.57?μg/mL). Compounds 6c-3 and 6g-3 possessed a para-nitro phenyl at the 6 position showed low Vero and HepG2 cells toxicity, turning out to be two excellent lead candidates for preclinical trials. In addition, in vitro Mt SD inhibitory assay indicates that Mt SD is at least one of the targets for their antitubercular activity. Thus, they may turn out to be promising multidrug-resistance-reversing agents.