Development of New Thiophene-Containing Triaryl Pyrazoline Derivatives as PI3Kγ Inhibitors.

ABSTRACT: A series of new thiophene-containing triaryl pyrazoline derivatives, 3a-3t, were synthesized and evaluated regarding PI3K inhibition activity and anti-tumor potency based on a trial of introducing significant moieties, including pyrazoline and thiophene, and simplifying the parallel ring structures. Most of the tested compounds indicated potent PI3K inhibitory potency, with this series of compounds showing more potency for PI3Kγ than PI3Kα. The top hit 3s seemed more potent than the positive control LY294002 on inhibiting PI3Kγ (IC₅₀ values: 0.066 μM versus 0.777 μM) and more selective from PI3Kα (Index values: 645 versus 1.74). It could be inferred that the combination of para- and meta-, as well as the modification of the electron-dona

SUBMITTER: Yang B 

PROVIDER: S-EPMC9027920 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature