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 ...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.展开更多
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 integr...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.展开更多
文摘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.
基金supported by grants from the National Natural Science Foundation of China(Nos.22222702,22107016,22107017 and 21907011)the Fundamental Research Funds for the Central Universities(No.2022CDJQY-001)+3 种基金Beijing National Laboratory for Molecular Sciences(No.BNLMS202104)the Natural Science Foundation of Chongqing(Nos.cstc2020jcyj-jqX0009,cstc2021jcyjmsxmX0016 and cstc2021jcyj-cxttX0002)High-end Foreign Expert Introduction Program(No.G2022165020L)Shenzhen Innovation Center for Small Molecule Drug Discovery Co.(No.H20220687).
文摘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.