Evaluation of Larger Side-Group Functionalities and the Side/End-Group Interplay in Ritonavir-Like Inhibitors of CYP3A4.

ABSTRACT: A new series of 13 ritonavir-like inhibitors of human drug-metabolizing CYP3A4 was rationally designed to study the R₂ side-group and R₃ end-group interplay when the R₁ side-group is represented by phenyl. Spectral, functional, and structural characterization showed no improvement in the binding affinity and inhibitory potency of R₁/R₂-phenyl inhibitors upon elongation and/or fluorination of R₃-Boc (tert-butyloxycarbonyl) or its replacement with benzenesulfonyl. When R₃ is pyridine, the impact of R₂-phenyl-to-indole/naphthalene substitution was multidirectional and highly dependent on side-group stereo configuration. Overall, the R₂-naphthalene/R₃-pyridine containing 2f (R/S) was t

SUBMITTER: Samuels ER 

PROVIDER: S-EPMC11749023 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature