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Bioorg Med Chem Lett. 2012 Oct 1;22(19):6286-91. doi: 10.1016/j.bmcl.2012.07.077. Epub 2012 Aug 8.

Imidazopyridazinones as novel PDE7 inhibitors: SAR and in vivo studies in Parkinson's disease model.

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Glenmark Pharmaceuticals Limited, Navi Mumbai, Maharashtra 400709, India.


The synthesis and structure-activity relationship studies of a series of compounds from imidazopyridazinone scaffold as PDE7 inhibitors are disclosed. Potent analogs such as compounds 7 (31nM), 8 (27nM), and 9 (12nM) were identified. The PDE selectivity and pharmacokinetic profile of compounds 7, 8 and 9 are also disclosed. The adequate CNS penetration of compound 7 in mice allowed it to be tested in the MPTP induced PD model and haloperidol induced catalepsy model to probe the differential pharmacology of PDE7 in the striatal pathway.

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