Selected Recent Work on Endo-Functionalization of Cylindrical Macrocyclic Artificial Receptors for Mimicking Protein–Ligand Interactions

In medicinal chemistry, a significant part of the process involves modifying the way a small molecule interacts with a target receptor, which is typically a protein. The objective is usually to enhance or dampen these interactions to achieve the desired therapeutic outcome. To gain a better understanding of these interactions, researchers have utilized functionalized macrocyclic receptors as models for mimicking protein binding pockets. Recent advancements in the functionalization of synthetic cylindrical and vase-shaped cylindrical macrocyclic receptors, including cavitands, calixpyrroles, naphthotubes, and pillar [1] arene-derivatives, among others, have been noteworthy and thought-provoking. In this short review, we present selected examples from a medicinal chemist’s perspective, with an emphasis on the endo-functionalization of cylindrical and vase-shaped cylindrical macrocyclic receptors and their binding features in model protein–ligand interactions.