55197-25-6

Upstream product

• 873-62-1 m-cyanophenol 
• 105-36-2 ethyl bromoacetate 

Downstream Products

• 57928-93-5 3-[(2-hydroxyethyl)oxy]benzonitrile 
• 1879-58-9 2-(3-cyanophenoxy) acetic acid 
• 935759-22-1 5-methyl-4-oxo-N-[(3-{[2-(1H-1,2,4-triazol-3-yloxy)ethyl]-oxy}phenyl)methyl]-3,4-dihydro-thieno[2,3-d]pyrimidine-2-carboxamide 
• 935760-22-8 1-{3-[(2-{[1-(triphenylmethyl)-1H-1,2,4-triazol-3-yl]oxy}-ethyl)oxy]phenyl}methanamine 
• 935760-21-7 3-[(2-{[1-(triphenylmethyl)-1H-1,2,4-triazol-3-yl]oxy}ethyl)-oxy]benzonitrile 
• 935759-63-0 5-(4-methoxyphenyl)-4-oxo-N-{3-[2-(1H-1,2,4-triazol-3-yloxy)ethoxy]benzyl}-3,4-dihydro-thieno[2,3-d]pyrimidine-2-carboxamide 
• 935759-57-2 5-(3-methoxyphenyl)-4-oxo-N-{3-[2-(1H-1,2,4-triazol-3-yloxy)ethoxy]benzyl}-3,4-dihydro-thieno[2,3-d]pyrimidine-2-carboxamide 
• 935759-54-9 5-(2-methoxyphenyl)-4-oxo-N-{3-[2-(1H-1,2,4-triazol-3-yloxy)ethoxy]benzyl}-3,4-dihydro-thieno[2,3-d]pyrimidine-2-carboxamide 
• 935759-61-8 5-(4-chlorophenyl)-4-oxo-N-{3-[2-(1H-1,2,4-triazol-3-yloxy)-ethoxy]benzyl}-3,4-dihydro-thieno[2,3-d]pyrimidine-2-carboxamide 
• 935759-53-8 5-(2-chlorophenyl)-4-oxo-N-{3-[2-(1H-1,2,4-triazol-3-yloxy)-ethoxy]benzyl}-3,4-dihydro-thieno[2,3-d]pyrimidine-2-carboxamide 

Relevant academic research and scientific papers

A Comparative Assessment Study of Known Small-Molecule Keap1-Nrf2 Protein-Protein Interaction Inhibitors: Chemical Synthesis, Binding Properties, and Cellular Activity

Inhibiting the protein-protein interaction (PPI) between the transcription factor Nrf2 and its repressor protein Keap1 has emerged as a promising strategy to target oxidative stress in diseases, including central nervous system (CNS) disorders. Numerous non-covalent small-molecule Keap1-Nrf2 PPI inhibitors have been reported to date, but many feature suboptimal physicochemical properties for permeating the blood-brain barrier, while others contain problematic structural moieties. Here, we present the first side-by-side assessment of all reported Keap1-Nrf2 PPI inhibitor classes using fluorescence polarization, thermal shift assay, and surface plasmon resonance - and further evaluate the compounds in an NQO1 induction cell assay and in counter tests for nonspecific activities. Surprisingly, half of the compounds were inactive or deviated substantially from reported activities, while we confirm the cross-assay activities for others. Through this study, we have identified the most promising Keap1-Nrf2 inhibitors that can serve as pharmacological probes or starting points for developing CNS-active Keap1 inhibitors.

Discovery of novel, highly potent, and selective matrix metalloproteinase (MMP)-13 inhibitors with a 1,2,4-triazol-3-yl moiety as a zinc binding group using a structure-based design approach

On the basis of a superposition study of X-ray crystal structures of complexes of quinazoline derivative 1 and triazole derivative 2 with matrix metalloproteinase (MMP)-13 catalytic domain, a novel series of fused pyrimidine compounds which possess a 1,2,4-triazol-3-yl group as a zinc binding group (ZBG) was designed. Among the herein described and evaluated compounds, 31f exhibited excellent potency for MMP-13 (IC50 = 0.036 nM) and selectivities (greater than 1,500-fold) over other MMPs (MMP-1, -2, -3, -7, -8, -9, -10, and -14) and tumor necrosis factor-α converting enzyme (TACE). Furthermore, the inhibitor was shown to protect bovine nasal cartilage explants against degradation induced by interleukin-1 and oncostatin M. In this article, we report the discovery of extremely potent, highly selective, and orally bioavailable fused pyrimidine derivatives that possess a 1,2,4-triazol-3-yl group as a novel ZBG for selective MMP-13 inhibition.

HETEROCYCLIC AMIDE COMPOUND AND USE THEREOF

The present invention provides a novel amide compound represented by the following formula, which has a matrix metalloproteinase inhibitory activity and is useful as a pharmaceutical agent. wherein each symbol is as defined in the specification.