64310-32-3

Upstream product

• 122-01-0 4-chloro-benzoyl chloride 
• 79-19-6 thiosemicarbazide 
• 333-20-0 potassium thioacyanate 
• 536-40-3 4-chlorobenzoic acid hydrazide 
• 74-11-3 para-chlorobenzoic acid 
• 2290-65-5 trimethylsilyl isothiocyanate 
• 1126-46-1 Methyl 4-chlorobenzoate 
• 1147550-11-5 ammonium thiocyanate 

Downstream Products

• 855737-94-9 1-(4-chloro-benzoyl)-S-methyl-iso thiosemicarbazide 
• 47298-24-8 4-chloro-benzoic acid N'-(4-amino-5-phenyl-thiazol-2-yl)-hydrazide 
• 81516-43-0 7-methyl-2-(4-chlorophenyl)-5H-1,3,4-thiadiazolo<3,2-a>pyrimidin-5-one 
• 129886-20-0 2-(p-chlorobenzoyl) hydrazono-4-thiazolidinone 
• 76700-02-2 2-(p-Chloro-benzoyl)-hydrazino-4,5,6,7-tetrahydrobenzothiazole 
• 259243-23-7 2-(4-chlorophenyl)-6-benzylidenethiazolo[3,2:b]-1,2,4-triazol-5(6H)-one 
• 105492-94-2 [5-(4-Chloro-phenyl)-[1,3,4]thiadiazol-2-yl]-(7-chloro-quinolin-4-yl)-amine 
• 76700-13-5 3-(p-Chlorophenyl)-5,6,7,8-tetrahydro-s-triazolo-<3,4-b>benzothiazole 
• 1276032-80-4 5-p-chlorophenyl-3-(β-D-glucopyranosylthio)-1,2,4-triazole 
• 1276032-70-2 5-p-chlorophenyl-3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosylthio)-1,2,4-triazole 
• 1363773-45-8 3-[4-(3-Chlorophenyl)piperazino]propyl [5-(4-chlorophenyl)-4H-1,2,4-triazol-3-yl]sulfide 
• 1363773-46-9 5-(4-chlorophenyl)-4H-1,2,4-triazol-3-yl 3-[4-(2-pyrimidinyl)piperazino]propyl sulfide 
• 1383783-64-9 4-(2-{[5-(4-chlorophenyl)-4H-1,2,4-triazol-3-yl]thio}ethoxy)benzaldehyde 
• 132719-40-5 2-(4-Chlorphenyl)-6-ethoxycarbonyl-5-methyl-thiazolo<3,2-b>-1,2,4-triazol 

Relevant academic research and scientific papers

Development of phenyltriazole thiol-based derivatives as highly potent inhibitors of DCN1-UBC12 interaction

Defective in cullin neddylation 1(DCN1) is a co-E3 ligase that is important for cullin neddylation. Dysregulation of DCN1 highly correlates with the development of various cancers. Herein, from the initial high-throughput screening, a novel hit compound 5a containing a phenyltriazole thiol core (IC50 value of 0.95 μM for DCN1-UBC12 interaction) was discovered. Further structure-based optimization leads to the development of SK-464 (IC50 value of 26 nM). We found that SK-464 not only directly bound to DCN1 in vitro, but also engaged cellular DCN1, suppressed the neddylation of cullin3, and hindered the migration and invasion of two DCN1-overexpressed squamous carcinoma cell lines (KYSE70 and H2170). These findings indicate that SK-464 may be a novel lead compound targeting DCN1-UBC12 interaction.

Synthesis and preliminary anticancer activity assessment of n-glycosides of 2-amino-1,3,4-thiadiazoles

The addition of 2-amino-1,3,4-thiadiazole derivatives with parallel iodination of differ-ently protected glycals has been achieved using a double molar excess of molecular iodine under mild conditions. The corresponding thiadiazole derivatives of N-glycosides were obtained in good yields and anomeric selectivity. The usage of iodine as a catalyst makes this method easy, inexpen-sive, and successfully useable in reactions with sugars. Thiadiazole derivatives were tested in a panel of three tumor cell lines, MCF-7, HCT116, and HeLa. These compounds initiated biological response in investigated tumor models in a different rate. The MCF-7 is resistant to the tested com-pounds, and the cytometry assay indicated low increase in cell numbers in the sub-G1 phase. The most sensitive are HCT-116 and HeLa cells. The thiadiazole derivatives have a pro-apoptotic effect on HCT-116 cells. In the case of the HeLa cells, an increase in the number of cells in the sub-G1-phase and the induction of apoptosis was observed.

Design and development of 1,3,5-triazine-thiadiazole hybrids as potent adenosine A2A receptor (A2AR) antagonist for benefit in Parkinson's disease

Various studies showed adenosine A2A receptors (A2ARs) antagonists have profound therapeutic efficacy in Parkinsons Disease (PD) by improving dopamine transmission, thus being active in reversing motor deficits and extrapyramidal symptoms related to the disease. Therefore, in the presents study, we have showed the development of novel 1,3,5-triazine-thiadiazole derivative as potent A2ARs antagonist. In the radioligand binding assay, these molecules showed excellent binding affinity with A2AR compared to A1R, with significant selectivity. Results suggest, compound 7e as most potent antagonist of A2AR among the tested series. In docking analysis with A2AR protein model, compound 7e found to be deeply buried into the cavity of receptor lined via making numerous interatomic contacts with His264, Tyr271, His278, Glu169, Ala63, Val84, Ile274, Met270, Phe169. Collectively, our study demonstrated 1,3,5-triazine-thiadiazole hybrid as a highly effective scaffold for the design of new A2A antagonists.

Novel panaxadiol triazole derivatives induce apoptosis in HepG-2 cells through the mitochondrial pathway

In this study, we introduced 1, 2, 4-triazole groups into panaxadiol (PD) to obtain 18 panaxadiol triazole derivatives. Five cancer cells and one normal cell were evaluated for cytotoxicity by MTT assay. The results showed that most of the derivatives could inhibit cancer cell proliferation, and the anti-proliferative activity of compound A1 was the most significant. For HepG-2 cells, the IC50 value was 4.21 ± 0.54 μM, which was nearly 15 times higher than the activity of PD. Further studies showed that compound A1 could induce apoptosis in HepG-2 cells, and could enhance the expression of Cl-caspase-3, Cl-caspase-9 and Cl-PARP. Moreover, Western blot analysis showed that after treating HepG-2 cells with compound A1, the expression of p53 protein was increased and the ratio of Bax/Bcl-2 was gradually increased. The cytoplasmic Bax is then translocated to the mitochondria, causing the release of Cyt c protein. Therefore, the results indicate that compound A1 induces apoptosis through the mitochondrial pathway and can be used the potential to develop new anti-proliferative agents.

Identification of 1,2,4-triazoles as new thymidine phosphorylase inhibitors: Future anti-tumor drugs

Thymidine phosphorylase (TP) is over expressed in several solid tumors and its inhibition can offer unique target suitable for drug discovery in cancer. A series of 1,2,4-triazoles 3a–3l has been synthesized in good yields and subsequently inhibitory potential of synthesized triazoles 3a–3l against thymidine phosphorylase enzyme was evaluated. Out of these twelve analogs five analogues 3b, 3c, 3f, 3l and 3l exhibited a good inhibitory potential against thymidine phosphorylase. Inhibitory potential in term of IC50 values were found in the range of 61.98 ± 0.43 to 273.43 ± 0.96 μM and 7-Deazaxanthine was taken as a standard inhibitor with IC50 = 38.68 ± 4.42 μM. Encouraged by these results, more analogues 1,2,4-triazole-3-mercaptocarboxylic acids 4a–4g were synthesized and their inhibitory potential against thymidine phosphorylase was evaluated. In this series, six analogues 4b–4g exhibited a good inhibitory potential in the range of 43.86 ± 1.11–163.43 ± 2.03 μM. Angiogenic response of 1,2,4-triazole acid 4d was estimated using the chick chorionic allantoic membrane (CAM) assay. In the light of these findings, structure activity relationship and molecular docking studies of selected triazoles to determine the key binding interactions was discussed. Docking studies demonstrate that synthesized analogues interacted with active site residues of thymidine phosphorylase enzyme through π-π stacking, thiolate and hydrogen bonding interactions.

Design, synthesis, and negative inotropic evaluation of 4-phenyl-1H-1,2,4-triazol-5(4H)-one derivatives containing triazole or piperazine moieties

In this study, four novel series of 4-phenyl-1H-1,2,4-triazol-5(4H)-one derivatives containing triazole or piperazine moieties were designed, synthesized, and evaluated for negative inotropic activity by measuring the left atrium stroke volume in isolated rabbit heart preparations. Almost all of the compounds showed an ability to moderate the cardiac workload by decreasing the heart rate and contractility. Among them, 7h was found to be the most potent with a change in stroke volume of ?48.22?±?0.36% at a concentration of 3?×?10?5?mol/L (metoprolol: ?9.74?±?0.14%). The cytotoxicity of these compounds was evaluated using the human cervical cancer cell line HeLa, the liver cancer cell line Hep3B, and the human normal hepatic cell line LO2. A preliminary study of the mechanism of action for the compound 7h on the regulation of atrial dynamics with ATP-sensitive K+ channel and L-type Ca2+ channel blockers glibenclamide and nifedipine was performed in the isolated perfused beating rabbit atria.

Efficient three-component synthesis of N-alkyl-3, 6-diaryl-[1, 2, 4]triazolo[4, 3-b][1, 2, 4]triazin-7-amines under solvent-free condition

A simple, efficient and environment-friendly approach is described for the synthesis of N-alkyl-3, 6-diaryl-[1, 2, 4]triazolo[4, 3-b][1, 2, 4]triazin-7-amines based on three-component reaction between 5-aryl-4H-1, 2, 4-triazole-3, 4-diamine, isocyanide and aldeyhde under solvent-free condition. The products are obtained in moderate to good yields and are in a state of high purity.

Synthesis and biological evaluation of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione as antimycobacterial agents

Resistance among dormant mycobacteria leading to multidrug-resistant and extremely drug-resistant tuberculosis is one of the major threats. Hence, a series of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione derivatives (4a–5c) have been synthesized and screened for their antitubercular activity against Mycobacterium tuberculosis H37Ra (H37Ra). The triazolethiones 4b and 4v showed high antitubercular activity (both MIC and IC50) against the dormant H37Ra by in vitro and ex vivo. They were shown to have more specificity toward mycobacteria than other Gram-negative and Gram-positive pathogenic bacteria. The cytotoxicity was almost insignificant up to 100?μg/ml against THP-1, A549, and PANC-1 human cancer cell lines, and solubility was high in aqueous solution, indicating the potential of developing these compounds further as novel therapeutics against tuberculosis infection.

Thiazole triazole-6-acetamide derivative and application

The invention discloses a thiazole [3,2-b] [1,2,4]-triazole-6-acetamide derivative as shown in formula I or a pharmaceutically acceptable hydrate and salt thereof. The derivative comprises a stereisomer or tautomer thereof; R1 in the formula I is hydrogen, methyl, halogen, hydroxy, methoxy group, acetyl, propionyl, nitro or alkoxy; R2 and R3 are independently selected from C1-C6 alkyl or R2 and R3 and nitrogen atoms connected with the R2 and R3 are formed into pyrryl, piperidyl, morpholinyl, N-methyl piperazine and N-phenylpiperazine. The thiazole [3,2-b] [1,2,4]-triazole-6-acetamide derivative disclosed by the invention has an obvious restraining function to acetylcholin esterase and is used for enhancing the memory of the patients suffering from dementia and Alzheimer's disease. The invention also relates to a preparation method of the compound and application of the compound for preparing the drug for treating the senile dementia.

6-methyl-thiazole triazole-5-formamide derivative and application

The invention discloses a 6-methyl-thiazole [3,2-b] [1,2,4]-triazole-5-formamide derivative as shown in formula I or pharmaceutically acceptable hydrate and salt thereof, including stereisomer or tautomer thereof. In the formula I, R1 is hydrogen, methyl, halogen, hydroxy, methoxyl, acetyl, propionyl, nitryl or alkoxy; R2 and R3 are independently selected from C1-C6 alkyl; or R2, R3 and nitrogen atoms connected with R2 and R3 form pyrrolyl, piperidyl, morpholinyl, N-methyl piperazine and N-(4-bromophenyl) piperazine. The 6-methyl-thiazole [3,2-b] [1,2,4]-triazole-5-formamide derivative disclosed by the invention is used as a vascular endothelial growth factor protein tyrosine kinase inhibitor for treating and preventing various cancers.