Metal-Binding Isosteres as New Scaffolds for Metalloenzyme Inhibitors.

ABSTRACT: The principle of isosteres or bioisosteres in medicinal chemistry is a central and essential concept in modern drug discovery. For example, carboxylic acids are often replaced by bioisosteres to mitigate issues related to lipophilicity or acidity while retaining acidic characteristics in addition to hydrogen bond donor/acceptor abilities. Separately, the development of metal-binding pharmacophores (MBPs) for binding to the active site metal ion in metalloenzymes of therapeutic interest is an emerging area in the realm of fragment-based drug discovery (FBDD). The direct application of the bioisostere concept to MBPs has not been well-described or systematically investigated. Herein, the picolinic acid MBP is used as a case study for the development of MBP isosteres (so-called MBIs). Many of

SUBMITTER: Dick BL 

PROVIDER: S-EPMC6289299 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature