PDE4-IN-20 is a selective submicromolar phosphodiesterase-4 ( PDE4 ) inhibitor with anti-TNF-α properties. PDE4-IN-20 exhibits significant biological activity in vitro and in vivo. The mechanism of action of PDE4-IN-20 is supported by molecular modeling studies, which reveal its binding mode with PDE4. PDE4-IN-20 was optimized in further conformational analysis and showed pharmacological characteristics similar to those of known PDE4 inhibitors.