1404052-52-3

Upstream product

• 611-17-6 1-bromomethyl-2-chlorobenzene 
• 37545-34-9 5-(2-pyrazinyl)-1,3,4-thiadiazole-2-thiol 
• 37545-37-2 potassium 2-(pyrazine-2-carbonyl)hydrazinecarbodithioate 
• 6164-79-0 methyl pyrazine-2-carboxylate 
• 768-05-8 pyrazine-2-carbohydrazide 
• 611-19-8 1-chloro-2-(chloromethyl)benzene 

Relevant academic research and scientific papers

Yoda1 analogue (Dooku1) which antagonizes Yoda1-evoked activation of Piezo1 and aortic relaxation

Background and Purpose: The mechanosensitive Piezo1 channel has important roles in vascular physiology and disease. Yoda1 is a small-molecule agonist, but the pharmacology of these channels is otherwise limited. Experimental Approach: Yoda1 analogues were generated by synthetic chemistry. Intracellular Ca2+ and Tl+ measurements were made in HEK 293 or CHO cell lines overexpressing channel subunits and in HUVECs, which natively express Piezo1. Isometric tension recordings were made from rings of mouse thoracic aorta. Key Results: Modification of the pyrazine ring of Yoda1 yielded an analogue, which lacked agonist activity but reversibly antagonized Yoda1. The analogue is referred to as Dooku1. Dooku1 inhibited 2?μM Yoda1-induced Ca2+-entry with IC50s of 1.3?μM (HEK 293 cells) and 1.5?μM (HUVECs) yet failed to inhibit constitutive Piezo1 channel activity. It had no effect on endogenous ATP-evoked Ca2+ elevation or store-operated Ca2+ entry in HEK 293 cells or Ca2+ entry through TRPV4 or TRPC4 channels overexpressed in CHO and HEK 293 cells. Yoda1 caused dose-dependent relaxation of aortic rings, which was mediated by an endothelium- and NO-dependent mechanism and which was antagonized by Dooku1 and analogues of Dooku1. Conclusion and Implications: Chemical antagonism of Yoda1-evoked Piezo1 channel activity is possible, and the existence of a specific chemical interaction site is suggested with distinct binding and efficacy domains.

A kind of [...]including pyrrole thiadiazole derivatives, their preparation and use

Provided are pyrazine ring- containing thiadiazole derivatives, which are characterized by the following general formula:, wherein R is for, and a preparation method. The pyrazine ring-containing thiadiazole derivatives can be used as potential antifungal

Design, synthesis and biological evaluation of heterocyclic azoles derivatives containing pyrazine moiety as potential telomerase inhibitors

Three series of novel heterocyclic azoles derivatives containing pyrazine (5a-5k, 8a-8k and 11a-11k) have been designed, synthesized, structurally determined, and their biological activities were evaluated as potential telomerase inhibitors. Among the oxadiazole derivatives, compound 5c showed the most potent biological activity against SW1116 cancer cell line (IC50 = 2.46 μM against SW1116 and IC50 = 3.55 μM for telomerase). Compound 8h performed the best in the thiadiazole derivatives (IC50 = 0.78 μM against HEPG2 and IC50 = 1.24 μM for telomerase), which was comparable to the positive control. While compound 11f showed the most potent biological activity (IC50 = 4.12 μM against SW1116 and IC50 = 15.03 μM for telomerase) among the triazole derivatives. Docking simulation by positioning compounds 5c, 8h and 11f into the telomerase structure active site was performed to explore the possible binding model. The results of apoptosis demonstrated that compound 8h possessed good antitumor activity against HEPG2 cancer cell line. Therefore, compound 8h with potent inhibitory activity in tumor growth inhibition may be a potential antitumor agent against HEPG2 cancer cell. Therefore, the introduction of oxadiazole, thiadiazole and triazole structures reinforced the combination of our compounds and the receptor, resulting in progress of bioactivity.