51285-05-3

Upstream product

• 19847-12-2 2-pyrazine carbonitrile 

Downstream Products

• 114346-87-1 C₁₂H₁₀N₄O₂ 
• 1401223-32-2 2-(4-butylphenoxy)-N-isopropyl-N-((3-pyrazin-2-yl)-1,2,4-oxadiazol-5-yl)methylacetamide 
• 1401223-31-1 N-isopropyl-2-(4-propylphenoxy)-N-((3-(pyrazin-2-yl)-1,2,4-oxadiazol-5-yl)methyl)acetamide 
• 1401223-74-2 (Z)-N'-(2-chloroacetoxy)pyrazine-2-carboximidamide 
• 1347755-41-2 2-methoxy-4-[3-(pyrazin-2-yl)-[1,2,4]oxadiazol-5-yl]-phenol 
• 1347755-38-7 4-[5-(2,5-dimethoxyphenyl)-[1,2,4]oxadiazol-3-yl]-pyridine 
• 114347-13-6 3-(pyrazin-2-yl)-4H-[1,2,4]oxadiazol-5-one 
• 345631-79-0 3-pyrazin-2-yl-4H-[1,2,4]oxadiazole-5-thione 

Relevant academic research and scientific papers

ATF6 MODULATORS AND USES THEREOF

Compounds (I) as modulators of Activating Transcription Factor 6 (ATF6) are provided. The compounds may find use as therapeutic agents for the treatment of diseases or disorders mediated by ATF6 and may find particular use in the treatment of viral infections, neurodegenerative diseases, vascular diseases, or cancer.

Synthesis and Anticancer Activity of Novel Actinonin Derivatives as HsPDF Inhibitors

Human mitochondrial peptide deformylase (HsPDF) is responsible for removing the formyl group from N-terminal formylmethionines of newly synthesized mitochondrial proteins and plays important roles in maintaining mitochondria function. It is overexpressed

In Vitro Assessment of Putative PD-1/PD-L1 Inhibitors: Suggestions of an Alternative Mode of Action

The programmed cell death protein 1 (PD-1) signaling axis is among the most important therapeutic targets in modern oncology. Aurigene Discovery Technologies Ltd. (Aurigene) has patented a series of peptidomimetic small molecules derived from the PD-1 pro

Structure-activity and structure-property relationships of novel Nrf2 activators with a 1,2,4-oxadiazole core and their therapeutic effects on acetaminophen (APAP)-induced acute liver injury

The antioxidant function induced by Nrf2 protects the liver from damage. We found a novel Nrf2 activator named compound 25 via structural modification of compound 1 we previously reported. In vitro, compound 25 induced Nrf2 transport into the nucleus and protected hepatocyte L02 cells from APAP-induced cytotoxicity via activating the Nrf2-ARE signaling pathway. In vivo, 25 exhibited therapeutic effects in a mouse model of acute liver injury induced by acetaminophen (APAP) by up-regulating Nrf2-dependent antioxidases and down-regulating liver injury markers in serum. Together, these results indicated that 25 is a potent Nrf2/ARE activator both in vitro and in vivo. The drug-like properties of compound 25 further revealed its potential for development as a therapeutic drug against acute liver injury.

Expanding Synthesizable Space of Disubstituted 1,2,4-Oxadiazoles

One-pot synthesis of 3,5-disubstituted 1,2,4-oxadiazoles from carboxylic acids and nitriles was optimized to parallel chemistry. The method was validated on a 141 member library; the desired products were recovered with a high success rate and in moderate yields. Practical application of the approach was demonstrated in the synthesis of bioactive compound pifexole and agonists of free fatty acid receptor 1. A library of 4 948 100 synthesizable drug-like 3,5-disubstituted 1,2,4-oxadiazoles was enumerated based on the method and available validated reagents.

Oxadiazole-isopropylamides as potent and noncovalent proteasome inhibitors

Screening of the 50 000 ChemBridge compound library led to the identification of the oxadiazole-isopropylamide 1 (PI-1833) which inhibited chymotrypsin-like (CT-L) activity (IC50 = 0.60 μM) with little effects on the other two major proteasome proteolytic activities, trypsin-like (T-L) and postglutamyl-peptide-hydrolysis-like (PGPH-L). LC-MS/MS and dialysis show that 1 is a noncovalent and rapidly reversible CT-L inhibitor. Focused library synthesis provided 11ad (PI-1840) with CT-L activity (IC50 = 27 nM). Detailed SAR studies indicate that the amide moiety and the two phenyl rings are sensitive toward modifications. Hydrophobic residues, such as propyl or butyl in the para position (not ortho or meta) of the A-ring and a m-pyridyl group as B-ring, significantly improve activity. Compound 11ad (IC50 = 0.37 μM) is more potent than 1 (IC50 = 3.5 μM) at inhibiting CT-L activity in intact MDA-MB-468 human breast cancer cells and inhibiting their survival. The activity of 11ad warrants further preclinical investigation of this class as noncovalent proteasome inhibitors.

PROTEASOME CHYMOTRYPSIN-LIKE INHIBITION USING PI-1833 ANALOGS

Focused library synthesis and medicinal chemistry on an oxadiazole- isopropylamide core proteasome inhibitor provided the lead compound that strongly inhibits CT-L activity. Structure activity relationship studies indicate the amide moiety and two phenyl rings are sensitive toward synthetic modifications. Only para-substitution in the A-ring was important to maintain potent CT-L inhibitory activity. Hydrophobic residues in the A-ring?s para-position and meta-pyridyl group at the B- ring significantly improved inhibition. The meta-pyridyl moiety improved cell permeability. The length of the aliphatic chain at the para position of the A-ring is critical with propyl yielding the most potent inhibitor, whereas shorter (i.e. ethyl, methyl or hydrogen) or longer (i.e. butyl, propyl and hexyl) chains demonstrating progressively less potency. Introduction of a stereogenic center next to the ether moiety (i.e. substitution of one of the hydrogens by methyl) demonstrated chiral discrimination in proteasome CT-L activity inhibition (the S-enantiomer was 35-40 fold more potent than the R-enantiomer)

Identification of a series of 4-[3-(quinolin-2-yl)-1,2,4-oxadiazol-5-yl] piperazinyl ureas as potent smoothened antagonist hedgehog pathway inhibitors

The Hedgehog (Hh-) signalling pathway is a key developmental pathway and there is a growing body of evidence showing that this pathway is aberrantly reactivated in a number of human tumors. Novel agents capable of inhibiting this pathway are sought, and an entirely novel series of smoothened (Smo) antagonists capable of inhibiting the pathway have been identified through uHTS screening. Extensive exploration of the scaffold identified the key functionalities necessary for potency, enabling potent nanomolar Smo antagonists like 91 and 94 to be developed. Optimization resulted in the most advanced compounds displaying low serum shift, clean off-targets profile, and moderate clearance in both rats and dogs. These compounds are valuable tools with which to probe the biology of the Hh-pathway.

New non-hydroxamic ADAMTS-5 inhibitors based on the 1,2,4-triazole-3-thiol scaffold

In this Letter we describe the design, synthesis, screening, and optimization of a new family of ADAMTS-5 inhibitors. These inhibitors display an original 1,2,4-triazole-3-thiol scaffold as a putative zinc binding-group. In vitro results are rationalized

Synthesis and antibacterial activity of novel pyridine and pyrazine derivatives obtained from amidoximes

(Chemical Equation Presented) The new pyridine, 4-pyridine N-oxide and pyrazine derivatives exhibiting an antibacterial activity have been synthesized. Amidoximes were transformed into N-hydroxyimidoyl chlorides and then into appropriate oximes. Upon treatment of pyridinecaboxamidoximes with methyl iodide 1-methylpyridynium iodides were formed. Reaction of amidoximes with various carbamoyl chlorides led to corresponding 5-aminocarbonyl-1,2,4-oxadiazoles. Some of carboxamides have undergone thermal decarboxylation to tertiary amines. The newly synthesized compounds were tested in vitro for their tuberculostatic activity. MIC of the most active compound 9 was 12.5 μg/mL for H 37Rv strain. Their activity towards 25 strains of anaerobic and 25 strains of aerobic bacteria was also studied. Derivative 18 was active against both aerobic and anaerobic types of the bacteria.