85106-47-4

Upstream product

• 100-09-4 4-methoxybenzoic acid 
• 94-30-4 ethyl 4-methoxybenzoate 
• 85103-41-9 potassium N-(4-methoxybenzoyl)hydrazinecarbodithioate 
• 3290-99-1 4-methoxybenzoic acid hydrazide 
• 10364-93-9 1-(4-methoxybenzoyl)-imidazole 
• 36209-49-1 4-amino-5-(4-methoxyphenyl)-2,3-dihydro-4H-1,2,4-triazole-3-thione 
• 2632-13-5 2-Bromo-4'-methoxyacetophenone 
• 36209-49-1 4-amino-5-(4-methoxyphenyl)-4H-1,2,4-triazole-3-thiol 

Relevant academic research and scientific papers

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.

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.

Exploration of a library of triazolothiadiazole and triazolothiadiazine compounds as a highly potent and selective family of cholinesterase and monoamine oxidase inhibitors: Design, synthesis, X-ray diffraction analysis and molecular docking studies

There is a high demand for the collection of small organic molecules (especially N-heterocycles) with diversity and complexity in the process of drug discovery. This need for privileged scaffolds in medicinal research gives an impetus for the development of nitrogen-containing compounds which are widely encountered in natural products, drugs and pharmaceutically active compounds. In this context, a diverse library of new triazolothiadiazole (4a-l) and triazolothiadiazine (5a-p) compounds was designed, synthesized and evaluated as potent and selective inhibitors of electric eel acetylcholinesterase (EeAChE) and horse serum butyrylcholinesterase (hBChE) by Ellman's method using neostigmine and donepezil as standard inhibitors. Among the screened triazolothiadiazoles, 4j emerged as a lead candidate showing the highest inhibition with an outstanding IC50 value of 0.117 ± 0.007 μM against AChE, which is ～139-fold greater inhibitory efficacy as compared to neostigmine, whereas 4k displayed ～506-fold strong inhibition with IC50 of 0.056 ± 0.001 μM against BChE. In the triazolothiadiazine series, 5j and 5e depicted a clear selectivity towards EeAChE with IC50 values of 0.065 ± 0.005 and 0.075 ± 0.001 μM, respectively, which are ～250- and ～218-fold stronger inhibition as compared to neostigmine (IC50 = 16.3 ± 1.12 μM). In addition, the synthesized compounds were also tested for their monoamine oxidase (MAO-A and MAO-B) inhibition, where 4a from the triazolothiadiazole series delivered the highest potency against MAO-A with an IC50 value of 0.11 ± 0.005 μM which is ～33-fold higher inhibition as compared to the standard inhibitor, clorgyline (IC50 = 3.64 ± 0.012 μM), whereas compound 5c from the triazolothiadiazine series turned out to be a lead inhibitor with an IC50 value of 0.011 ± 0.001 μM which is ～330-fold stronger inhibition. Moreover, compounds 4b (triazolothiadiazole series) and 5o (triazolothiadiazine series) were identified as lead inhibitors against MAO-B. Molecular modelling studies were performed against human AChE and BChE to observe the binding site interactions of these compounds.

Identification of a potent new chemotype for the selective inhibition of PDE4

A series of substituted 3,6-diphenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines were prepared and analyzed as inhibitors of phosphodiesterase 4 (PDE4). Synthesis, structure-activity relationships, and the selectivity of a highly potent analogue against related phosphodiesterase isoforms are presented.

Potential broad spectrum anthelmintics. IV: Design, synthesis, and antiparasitic screening of certain 3,6-disubstituted-(7H)-s-triazolo-[3,4-b][1,3,4]thiadiazine derivatives

A series of 3,6-disubstituted-(7H)-s-triazolo[3,4-b][1,3,4]-thiadiazine derivatives were prepared. The compounds were designed to obtain structural similarities and/or bear isosteric relation with certain fused systems encountered in some well-known antip