Covalent MiniFrags (Live)

This is a library of small heterocyclic electrophiles. These are essentially covalent MiniFrags, comprising five and six-membered nitrogen-containing heterocycles with electron-withdrawing character that activates small electrophilic substituents (halogens, ethynyl, vinyl and nitrile groups). X-ray screening of ultra-low-molecular-weight ligands (MiniFrags) was successfully applied to identify viable chemical starting points for a variety of drug targets. The covalent version goes further and might provide powerful starting points for covalent ligand discovery, coupling the advantages of the MiniFrags with the fixed binding modes due to the minimal size warheads of 1 or 2 heavy atoms. The library contains not only small electrophilic heterocycles, but also their N-quaternized analogues with increased reactivity.

This library is commercially available from Enamine.

Compounds

• 141 covalent heterocyclic fragments with the average MW of 141.6 Da
  • 84 heterocyclic electrophiles and 57 quaternized analogues
• 500 mM d6-DMSO

SMILES: click to download the CovMiniFrags plate map

For follow-ups, please contact: György M Keserű

PUBLICATIONS to cite:

1. Aaron B. Keeley, Aleksandra Kopranovic, Vincenzo Di Lorenzo, Péter Ábrányi-Balogh, Niklas Jänsch, Linh N. Lai, László Petri, Zoltán Orgován, Daniel Pölöske, Anna Orlova, András György Németh, Charlotte Desczyk, Tímea Imre, Dávid Bajusz, Richard Moriggl, Franz-Josef Meyer-Almes, and György M. Keserü, Electrophilic MiniFrags Revealed Unprecedented Binding Sites for Covalent HDAC8 Inhibitors, J. Med. Chem., 2024, 67, 1, 572–585.

2. Aaron Keeley, László Petri, Péter Ábrányi-Balogh, György M Keserű, Covalent fragment libraries in drug discovery, Drug Discovery Today, 2020, 25, 983-996.

3. Aaron Keeley, Péter Ábranyi-Balogh and György M Keserű, Design and characterization of a heterocyclic electrophilic fragment library for the discovery of cysteine-targeted covalent inhibitors, MedChemComm, 2019, 10, 263-267.

ACKNOWLEDGEMENT text to use: 

Covalent MiniFrag library was provided by the Keserű lab at RCNS, Hungary (http://medchem.ttk.hu).