Macrocycles offer a unique opportunity to address some of the more challenging drug targets and I've highlighted this on a couple of pages on the Drug Discovery Resources, here and here.

Macrocycles lie outside the usual "drug space" delineated by the Rule-of-5 and macrocycles can adopt different conformation in various media, hiding polar atoms or forming intramolecular hydrogen bonds, thus retaining good cell permeability and ADME properties

I recently got an email from ChemBridge highlighting a new 11,000 member Macrocyclic Library for screening. The general characteristics of compounds in the ChemBridge Macrocycle Library include:

• Molecular weight range up to 800
• Primary ring size ranging from 11 to 27 atoms
• Heterocyclic primary rings
• Scaffolds with and without peptidic backbone elements as part of the macrocyclic ring
• Scaffolds with and without fused rings as part of the primary macrocyclic ring