COMPOSITION AND METHODS FOR THE DESIGN AND DEVELOPMENT OF METALLO-ENZYME INHIBITORS

摘要

The present disclosure provides compounds having the general structure A or pharmaceutically acceptable salts thereof: R-X (A) wherein R is an alkyl or aryl moiety comprising heterocyclic structures; and X is a metal- chelatin group selected from: This disclosure further provides a focused library of compounds for use in the discovery and design of metallo-enzyme inhibitors. This fragment-based approach provides an assembly of a library of low molecular weight compounds (MW < 300 Da) containing a variety of potential metal-chelating groups. The identification of the inhibitory scaffolds among these compounds provides the initial hit fragments that may be optimized for affinity against a particular target using common medicinal chemistry, structure-based or NMR-based approaches.