More than 1.3 Million
Small Molecules, Macrocycles
and Fragments for Hit Generation

Macrocycles
Synthetic Macrocycles for Protein-Protein Interaction Inhibition and Other Difficult Targets

Macrocycles offer a novel approach for low druggability targets such as antimicrobial, antiviral and protein-protein interaction. Topologically, macrocycles have the unique ability to span large surface areas while remaining conformationally restricted compared to acyclic molecules of equivalent molecular weight. Macrocyclization reduces overall polarity and enhances membrane penetration. Taken together these attributes make macrocycles a powerful approach for any lead discovery program against challenging targets. Macrocycles are typically defined as a carbo- or, more likely, a heterocycle comprising 12 or more heavy atoms and are often perceived as difficult to synthesize and challenging to incorporate chemical diversity. Through focusing on solutions to the synthetic challenges the chemists at ChemBridge have produced a library of over 20,000 synthetic macrocycles that are in stock and available for purchase.

View the Macrocycle Library product sheet

Characteristics

ChemBridge has developed a diverse collection of synthetic macrocycles intended to be accessible to both industry and academic researchers for use in hit generation. ChemBridge chemists have developed synthetic strategies for the synthesis and functionalization of macrocyclic compounds based on novel macrocyclic scaffolds. A first set of approximately 7,000 macrocycles was launched, and ChemBridge has continued to increase the size of the macrocycle library each year based on novel designs incorporating proprietary fragments into the macrocycle rings. Currently, the Macrocycle Library represents more than 20,000. Researchers have the option to custom select from the Macrocycle Library or acquire the full library.

General characteristics of compounds in the ChemBridge Macrocycle Library include:

  • Molecular weight range up to 800 with the majority having MW 450 to 750
  • Primary ring size ranging from 11 to 27 atoms (based on shortest path / fewest bonds included in the primary ring) with the majority having primary ring sizes of 13 to 21 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
Macrocycle CNS Subset

An analysis of the initial 7,000 synthetic macrocycles produced by ChemBridge was performed to identify macrocycles that may be suitable for CNS research. A CNS MPO score approach was coupled with a detailed 3D conformational analysis (performed to examine the potential for formation of intramolecular hydrogen bonds). Data from the conformational analysis was used to adjust the HBD and TPSA values and resulting MPO score for each macrocycle to identify a subset with an “adjusted MPO” score ≥ 4.0. Vist the Macrocycle CNS Subset Macrocycle CNS Subset page for more information.

Format
  • Macrocyles can be custom selected
  • Compounds can be provided in 384-well and 96-well format plates and rack, inlcuding acoustic qualified plates
  • Compounds are available as DMSO solutions or dry films
  • Minimum purchase amount of 0.25 micromole for selections of 2,000 or more macrocycles; minimum purchase amount of 1 micromole for selections less than 2,000
Structure Files

For a file of structures, please contact ChemBridge Sales.