《Fragment-Based Approaches to the Development of Mycobacterium tuberculosis CYP121 Inhibitors》 was written by Kavanagh, Madeline E.; Coyne, Anthony G.; McLean, Kirsty J.; James, Guy G.; Levy, Colin W.; Marino, Leonardo B.; de Carvalho, Luiz Pedro S.; Chan, Daniel S. H.; Hudson, Sean A.; Surade, Sachin; Leys, David; Munro, Andrew W.; Abell, Chris. Application of 31938-07-5This research focused ontriazolyl phenol derivative preparation tuberculostatic development Mycobacterium CYP121 inhibitor. The article conveys some information:
The essential enzyme CYP121 is a target for drug development against antibiotic resistant strains of Mycobacterium tuberculosis. A triazol-1-yl phenol fragment 1 was identified to bind to CYP121 using a cascade of biophys. assays. Synthetic merging and optimization of 1 produced a 100-fold improvement in binding affinity, yielding lead compound 2 (KD = 15 μM). Deconstruction of 2 into its component retrofragments allowed the group efficiency of structural motifs to be assessed, the identification of more LE scaffolds for optimization and highlighted binding affinity hotspots. Structure-guided addition of a metal-binding pharmacophore onto LE retrofragment scaffolds produced low nanomolar (KD = 15 nM) CYP121 ligands. Elaboration of these compounds to target binding hotspots in the distal active site afforded compounds with excellent selectivity against human drug-metabolizing P450s. Anal. of the factors governing ligand potency and selectivity using X-ray crystallog., UV-vis spectroscopy, and native mass spectrometry provides insight for subsequent drug development. In the part of experimental materials, we found many familiar compounds, such as 2-(3-Bromophenyl)acetonitrile(cas: 31938-07-5Application of 31938-07-5)
2-(3-Bromophenyl)acetonitrile(cas: 31938-07-5) has been used in the synthesis of a series of aminoethylbiphenyls, novel 5-HT7 receptor ligands or 2-(1-cyano-1-(3-bromophenyl))methylidene-3-phenylthiazolidine-4,5-dione.Application of 31938-07-5
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts