6 research outputs found
Design and Synthesis of a Novel Series of Orally Bioavailable, CNS-Penetrant, Isoform Selective Phosphoinositide 3‑Kinase γ (PI3Kγ) Inhibitors with Potential for the Treatment of Multiple Sclerosis (MS)
The lipid kinase phosphoinositide
3-kinase γ (PI3Kγ) has attracted attention as a potential
target to treat a variety of autoimmune disorders, including multiple
sclerosis, due to its role in immune modulation and microglial activation.
By minimizing the number of hydrogen bond donors while targeting a
previously uncovered selectivity pocket adjacent to the ATP binding
site of PI3Kγ, we discovered a series of azaisoindolinones as
selective, brain penetrant inhibitors of PI3Kγ.
This ultimately led to the discovery of <b>16</b>, an orally
bioavailable compound that showed efficacy in murine experimental
autoimmune encephalomyelitis (EAE), a preclinical model of multiple
sclerosis
Design and Synthesis of a Novel Series of Orally Bioavailable, CNS-Penetrant, Isoform Selective Phosphoinositide 3‑Kinase γ (PI3Kγ) Inhibitors with Potential for the Treatment of Multiple Sclerosis (MS)
The lipid kinase phosphoinositide
3-kinase γ (PI3Kγ) has attracted attention as a potential
target to treat a variety of autoimmune disorders, including multiple
sclerosis, due to its role in immune modulation and microglial activation.
By minimizing the number of hydrogen bond donors while targeting a
previously uncovered selectivity pocket adjacent to the ATP binding
site of PI3Kγ, we discovered a series of azaisoindolinones as
selective, brain penetrant inhibitors of PI3Kγ.
This ultimately led to the discovery of <b>16</b>, an orally
bioavailable compound that showed efficacy in murine experimental
autoimmune encephalomyelitis (EAE), a preclinical model of multiple
sclerosis