67856-44-4

Upstream product

• 57-57-8 β-Propiolactone 
• 540-38-5 p-Iodophenol 
• 590-92-1 3-Bromopropionic acid 
• 107-94-8 chloropropionic acid 

Downstream Products

• 101714-35-6 6-iodo-2,3-dihydro-4H-benzopyran-4-one 
• 191228-69-0 O-tert-butyl-3-(4-iodophenoxy)propanohydroxamic acid 
• 107923-08-0 6-iodo-chroman-4-one-(2,4-dinitro-phenylhydrazone) 
• 1403863-82-0 N-tert-butoxy-3-(4-trimethylstannanylphenoxy)propionamide 

Relevant academic research and scientific papers

AMIDE COMPOUND HAVING BET PROTEOLYSIS-INDUCING ACTION AND MEDICINAL APPLICATION THEREOF

The present invention aims to provide a compound that: has an excellent cytotoxic action on cancer cells, excellent induction of BET protein degradation in cancer cells, and an excellent binding-inhibiting action on BET protein and acetylated histone; and is effective as an anti-cancer agent, a BET protein degradation-inducing agent, or a BET protein inhibiting agent. A compound indicated in general formula (I) or a pharmacologically acceptable salt thereof. {In the formula, each symbol is as outlined in the Description.}

Synthesis, evaluation and in silico molecular modeling of pyrroyl-1,3,4-thiadiazole inhibitors of InhA

Enoyl acyl carrier protein reductase (ENR) is an essential type II fatty acid synthase (FAS-II) pathway enzyme that is an attractive target for designing novel antitubercular agents. Herein, we report sixty-eight novel pyrrolyl substituted aryloxy-1,3,4-thiadiazoles synthesized by three-step optimization processes. Three-dimensional quantitative structure-activity relationships (3D-QSAR) were established for pyrrolyl substituted aryloxy-1,3,4-thiadiazole series of InhA inhibitors using the comparative molecular field analysis (CoMFA). Docking analysis of the crystal structure of ENR performed by using Surflex-Dock in Sybyl-X 2.0 software indicates the occupation of pyrrolyl substituted aryloxy 1,3,4-thiadiazole into hydrophobic pocket of InhA enzyme. Based on docking and database alignment rules, two computational models were established to compare their statistical results. The analysis of 3D contour plots allowed us to investigate the effect of different substituent groups at different positions of the common scaffold. In vitro testing of ligands using biological assays substantiated the efficacy of ligands that were screened through in silico methods.

An enthalpic basis of additivity in biphenyl hydroxamic acid ligands for stromelysin-1

Fragment based drug discovery remains a successful tool for pharmaceutical lead discovery. Although based upon the principle of thermodynamic additivity, the underlying thermodynamic basis is poorly understood. A thermodynamic additivity analysis was performed using stromelysin-1 and a series of biphenyl hydroxamate ligands identified through fragment additivity. Our studies suggest that, in this instance, additivity arises from enthalpic effects, while interaction entropies are unfavorable; this thermodynamic behavior is masked by proton transfer. Evaluation of the changes in constant pressure heat capacities during binding suggest that solvent exclusion from the binding site does not account for the dramatic affinity enhancements observed.

Biphenyl hydroxamate inhibitors of matrix metalloproteinases

Compounds of formula STR1 or a pharmaceutically acceptable salt thereof inhibit matrix metalloproteinases and TNFα secretion and are useful in the treatment of inflammatory disease states. Also disclosed are matrix metalloproteinases and TNFα secretion inhibiting compositions and a method for inhibiting matrix metalloproteinases and TNFα secretion.

Discovery of potent nonpeptide inhibitors of stromelysin using SAR by NMR

With the use of an NMR-based method, potent (IC50 25 nM) nonpeptide inhibitors of the matrix metalloproteinase stromelysin (MMP-3) were discovered. The method, called SAR by NMR (for structure-activity relationships by nuclear magnetic resonance), involves the identification, optimization, and linking of compounds that bind to proximal sites on a protein. Using this technique, two ligands that bind weakly to stromelysin (acetohydroxamic acid, K(D) = 17 mM; 3-(cyanomethyl)-4'-hydroxybiphenyl, K(D) = 0.02 mM) were identified. On the basis of NMR-derived structural information, the two fragments were connected to produce a 15 nM inhibitor of this enzyme. This compound was rapidly discovered (less than 6 months) and required only a minimal amount of chemical synthesis. These studies indicate that the SAR by NMR method can be effectively applied to enzymes to yield potent lead inhibitors-an important part of the drug discovery process.