Design, synthesis and SAR study of 3rd-generation taxoids bearing 3-CH₃, 3-CF₃O and 3-CHF₂O groups at the C2-benzoate position.

ABSTRACT: 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 positio

SUBMITTER: Wang C 

PROVIDER: S-EPMC7561017 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature