Macrocycle synthesis strategy based on step-wise “adding and reacting” three components enables screening of large combinatorial libraries
Mothukuri Ganesh Kumar, Sangram S. Kale, Carl L. Stenbratt, Alessandro Zorzi, J.-M. Vesin, Julien Bortoli Chapalay, Kaycie M. Deyle, Gerardo Turcatti, Laura Cendron, Alessandro Angelini, Christian Heinis
Abstract
= 4.2 ± 0.8 nM) that efficiently blocked blood coagulation in human plasma. Structure-activity relationship and X-ray crystallography analysis revealed that two of the three building blocks acted synergistically and underscored the importance of combinatorial screening in macrocycle development. The three-component library synthesis approach is general and offers a promising avenue to generate macrocycle ligands to other targets.
Topics & Concepts
Combinatorial chemistryComputer scienceChemistryChemical Synthesis and AnalysisClick Chemistry and ApplicationsComputational Drug Discovery Methods