The discovery of potent, selective, and orally bioavailable PDE9 inhibitors as potential hypoglycemic agents
Graphical abstract
Starting from the non-selective lead 1, the sequential use of library and directed synthesis led to the optimized PDE9 inhibitor 13.
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2021, European Journal of Medicinal ChemistryCitation Excerpt :PDE9 has more than twenty variants based on N-terminal alternative splicing and only one gene, PDE9A, which is expressed primarily in brain, spleen, intestinal cells, kidney, heart and vasculature [243]. PDE9 knockout mice has reduced insulin resistance, reduced weight gain and lower fat mass [244]. PDE9 inhibition also increases CNS cGMP in vivo.
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