Branch-Selective and Enantioselective Iridium-Catalyzed Alkene Hydroarylation via Anilide-Directed C–H Oxidative Addition

Tertiary benzylic stereocenters are accessed in high enantioselectivity by Ir-catalyzed branch selective addition of anilide <i>ortho</i>-C–H bonds across styrenes and α-olefins. Mechanistic studies indicate that the stereocenter generating step is reversible

Branch-Selective and Enantioselective Iridium-Catalyzed Alkene Hydroarylation via Anilide-Directed C–H Oxidative Addition

Tertiary benzylic stereocenters are accessed in high enantioselectivity by Ir-catalyzed branch selective addition of anilide <i>ortho</i>-C–H bonds across styrenes and α-olefins. Mechanistic studies indicate that the stereocenter generating step is reversible

Branch-Selective and Enantioselective Iridium-Catalyzed Alkene Hydroarylation via Anilide-Directed C–H Oxidative Addition

Tertiary benzylic stereocenters are accessed in high enantioselectivity by Ir-catalyzed branch selective addition of anilide <i>ortho</i>-C–H bonds across styrenes and α-olefins. Mechanistic studies indicate that the stereocenter generating step is reversible

Branch-Selective and Enantioselective Iridium-Catalyzed Alkene Hydroarylation via Anilide-Directed C–H Oxidative Addition

Tertiary benzylic stereocenters are accessed in high enantioselectivity by Ir-catalyzed branch selective addition of anilide <i>ortho</i>-C–H bonds across styrenes and α-olefins. Mechanistic studies indicate that the stereocenter generating step is reversible

Development of a Series of Pyrrolopyridone MAT2A Inhibitors

The optimization of an allosteric fragment, discovered by differential scanning fluorimetry, to an in vivo MAT2a tool inhibitor is discussed. The structure-based drug discovery approach, aided by relative binding free energy calculations, resulted in AZ’9567 (21), a potent inhibitor in vitro with excellent preclinical pharmacokinetic properties. This tool showed a selective antiproliferative effect on methylthioadenosine phosphorylase (MTAP) KO cells, both in vitro and in vivo, providing further evidence to support the utility of MAT2a inhibitors as potential anticancer therapies for MTAP-deficient tumors

Development of a Series of Pyrrolopyridone MAT2A Inhibitors

The optimization of an allosteric fragment, discovered by differential scanning fluorimetry, to an in vivo MAT2a tool inhibitor is discussed. The structure-based drug discovery approach, aided by relative binding free energy calculations, resulted in AZ’9567 (21), a potent inhibitor in vitro with excellent preclinical pharmacokinetic properties. This tool showed a selective antiproliferative effect on methylthioadenosine phosphorylase (MTAP) KO cells, both in vitro and in vivo, providing further evidence to support the utility of MAT2a inhibitors as potential anticancer therapies for MTAP-deficient tumors