PDE4 is an enzyme responsible for the hydrolysis of cyclic 3',5'-adenosine monophosphate (cAMP). PDE4 inhibitors are believed to be beneficial for the treatment of various inflammatory disease, because elevation of cAMP is known to suppress activation of inflammatory cells. Pyrrolo[1,2-b]pyridazine series of PDE4 inhibitors were discovered and optimization of the series led to the identification of ASP9831, a potent inhibitor with excellent oral bioavailability. ASP9831 significantly reduced the elevation of alanine aminotransferase (ALT) at 1.0 mg/kg in a rat model of D-galactosamine-induced acute hepatitis without delaying gastric emptying.

Design and synthesis of novel pyrrolo[1,2-<i>b</i>]pyridazine derivatives of phosphodiesterase 4 (PDE4) inhibitors

242nd National Meeting (2011)

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Design and synthesis of novel pyrrolo[1,2-b]pyridazine derivatives of phosphodiesterase 4 (PDE4) inhibitors