biostudies-literatureYang MFundamental Research Funds for the Central UniversitiesNatural Science Foundation of Liaoning Province of China2551-2565https://www.ebi.ac.uk/biostudies/studies/S-EPMC9518286biostudies-literatureUnknown37(1)The molecular chaperone HSP90 plays an essential role in cancer occurrence and development. Therefore, it is an important target for the development of anticancer drugs. 1,3-Dibenzyl-2-aryl imidazolidine (<b>8)</b> is a previously reported inhibitor of HSP90; however, its anticancer activity is poor. In this work, chemical modification of <b>8</b> led to the discovery of 2,4-diarylimidazoles and 2,4-bis(benzyloxy)-5-arylpyrimidines as two types of novel HSP90 N-terminal inhibitors. <b>16l</b> and <b>22k</b> exhibited antiproliferative activity against multiple breast cancer cell lines with IC₅₀ values at the low micromolar level. <b>16l</b> and <b>22k</b> induced significant degradation of the client proteins AKT and ERK and a lower level of the heat shock response in comparisonJournal of enzyme inhibition and medicinal chemistryDesign, synthesis, biological evaluation and molecular docking study of 2,4-diarylimidazoles and 2,4-bis(benzyloxy)-5-arylpyrimidines as novel HSP90 N-terminal inhibitors.PMC95182862020-MS-105DUT20LK20; DUT22YG111Cheng CLiu YLi YShi MLi CYang MYin LXue HfalseDesign, synthesis, biological evaluation and molecular docking study of 2,4-diarylimidazoles and 2,4-bis(benzyloxy)-5-arylpyrimidines as novel HSP90 N-terminal inhibitors.The molecular chaperone HSP90 plays an essential role in cancer occurrence and development. Therefore, it is an important target for the development of anticancer drugs. 1,3-Dibenzyl-2-aryl imidazolidine (<b>8)</b> is a previously reported inhibitor of HSP90; however, its anticancer activity is poor. In this work, chemical modification of <b>8</b> led to the discovery of 2,4-diarylimidazoles and 2,4-bis(benzyloxy)-5-arylpyrimidines as two types of novel HSP90 N-terminal inhibitors. <b>16l</b> and <b>22k</b> exhibited antiproliferative activity against multiple breast cancer cell lines with IC₅₀ values at the low micromolar level. <b>16l</b> and <b>22k</b> induced significant degradation of the client proteins AKT and ERK and a lower level of the heat shock response in comparison2022-01-01T00:00:00Z2022 Dec2026-05-28T00:35:48.639Z2025-04-19T05:15:14.09ZS-EPMC95182863612095710.1080/14756366.2022.2124407