Modular Click Chemistry Library:Searching for Better Functions

High throughput screening towards chemical libraries is the primary way to discover lead compounds in developing innovative drugs,especially new molecular entities.Accordingly,the preparation of chemical libraries is the key step for drug development.Now,con-ventional small molecule chemical libraries and DNA-encoded chemical libraries are the main models of chemical libraries for high-throughput screening.Recently,a new model of chemical library,calledmodular click chemistry library,was proposed,which gives us an alternative choice to construct chemical libraries for high throughput screening and exhibits broad prospects to accelerate drug development.Herein,this article mainly focuses on the strategy to prepare the modular click chemistry library.

Encoding and display technologies for combinatorial libraries in drug discovery:The coming of age from biology to therapy

Drug discovery is a sophisticated process that incorporates scientific innovations and cuttingedge technologies.Compared to traditional bioactivity-based screening methods,encoding and display technologies for combinatorial libraries have recently advanced from proof-of-principle experiments to promising tools for pharmaceutical hit discovery due to their high screening efficiency,throughput,and resource minimization.This review systematically summarizes the development history,typology,and prospective applications of encoding and displayed technologies,including phage display,ribosomal display,mRNA display,yeast cell display,one-bead one-compound,DNA-encoded,peptide nucleic acidencoded,and new peptide-encoded technologies,and examples of preclinical and clinical translation.We discuss the progress of novel targeted therapeutic agents,covering a spectrum from small-molecule inhibitors and nonpeptidic macrocycles to linear,monocyclic,and bicyclic peptides,in addition to antibodies.We also address the pending challenges and future prospects of drug discovery,including the size of screening libraries,advantages and disadvantages of the technology,clinical translational potential,and market space.This review is intended to establish a comprehensive high-throughput drug discovery strategy for scientific researchers and clinical drug developers.

Antimony salt-promoted cyclization facilitating on-DNA syntheses of dihydroquinazolinone derivatives and its applications

DNA-encoded chemical libraries technology has become a novel approach to finding hit compounds in early drug discovery.The chemical space in a DEL would be expanded to realize its full potential,especially when integrating privileged scaffold dihydroquinazoline that has demonstrated a variety of diverse bioactivities.Driven by the requirement of parallel combinatorial synthesis,we here report a facile synthesis of on-DNA dihydroquinazolinone from aldehyde and anthranilamide.This DNA-compatible reaction was promoted by antimony trichloride,which has been proven to accelerate the reaction and improve conversions.Notably,the broad substrate scope of aldehydes and anthranilamides was explored under the mild reaction condition to achieve moderate-to-excellent conversion yields.We further applied the reaction into on-DNA macrocyclization,obtaining macrocycles embedded dihydroquinazolinone scaffold in synthetically useful conversion yields.