biostudies-literatureWang CNatural Science Foundation of Guangdong Province, ChinaNational Cancer InstituteNCI NIH HHS103523https://www.ebi.ac.uk/biostudies/studies/S-EPMC7561017biostudies-literatureUnknown95It has been shown that inclusion of CF₃O and CHF₂O groups to drug candidates often improve their pharmacological properties, especially metabolic stability, membrane permeability and PK profile. Moreover, the unique non-spherical structure of the OCHF₂ group can provide interesting and beneficial characteristics. Accordingly, new 3rd-generation taxoids, bearing 3-OCF₃ or 3-OCF₂H (and 3-CH₃ for comparison) at the C2 benzoate moiety, were synthesized and their potencies against drug-sensitive and drug-resistant cancer cell lines examined. In this study, our previous SAR studies on 3rd-generation taxoids were expanded to disclose that CH₃, CF₃O and CHF₂O groups are well tolerated at this positioBioorganic chemistryDesign, synthesis and SAR study of 3rd-generation taxoids bearing 3-CH₃, 3-CF₃O and 3-CHF₂O groups at the C2-benzoate position.PMC7561017CA 1033142015B0202110122016A050502039R01 CA103314Ojima IBotchkina GIWang CYan SWang XSun YTaouil AKfalseDesign, synthesis and SAR study of 3rd-generation taxoids bearing 3-CH₃, 3-CF₃O and 3-CHF₂O groups at the C2-benzoate position.It has been shown that inclusion of CF₃O and CHF₂O groups to drug candidates often improve their pharmacological properties, especially metabolic stability, membrane permeability and PK profile. Moreover, the unique non-spherical structure of the OCHF₂ group can provide interesting and beneficial characteristics. Accordingly, new 3rd-generation taxoids, bearing 3-OCF₃ or 3-OCF₂H (and 3-CH₃ for comparison) at the C2 benzoate moiety, were synthesized and their potencies against drug-sensitive and drug-resistant cancer cell lines examined. In this study, our previous SAR studies on 3rd-generation taxoids were expanded to disclose that CH₃, CF₃O and CHF₂O groups are well tolerated at this positio2020-01-01T00:00:00Z2020 Jan2026-05-04T04:24:53.137Z2021-02-20T17:39:57ZS-EPMC75610173191130510.1016/j.bioorg.2019.103523