Division/Committee: [MEDI: Division of Medicinal Chemistry]

Macrocycles have emerged successfully as a versatile chemical modality in drug discovery. They are cyclic structures that are conformationally restricted, resulting in high affinity and selectivity. Despite this, they still maintain sufficient permeability to reach intracellular targets. There are several methodologies currently available for the discovery of novel macrocyclic hits, including structure-based rational design, screening of natural product-like libraries, and DNA-encoded chemical libraries (DEL). This session will focus on the increasing numbers of rationally designed macrocycles by medicinal chemists that have progressed into clinical trials. These macrocycles aim to tackle unmet medical needs in various therapeutic areas. Notably, these compounds have the remarkable ability to adapt their structure in response to environmental changes, known as 'chameleonic character'. It is crucial for designing drugs with high aqueous solubility and cell permeability. Recent shifts towards higher molecular weight drugs for novel targets have increased interest in molecular chameleons, particularly in macrocycles and cyclic peptides.

Abbas Walji

Merck Co Inc

Appearances