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

Bioorganic & Medicinal Chemistry Letters
2012.0

Abstract

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.

Knowledge Graph

Similar Paper

Imidazopyridazinones as novel PDE7 inhibitors: SAR and in vivo studies in Parkinson’s disease model
Bioorganic & Medicinal Chemistry Letters 2012.0
New imidazopyridines with phosphodiesterase 4 and 7 inhibitory activity and their efficacy in animal models of inflammatory and autoimmune diseases
European Journal of Medicinal Chemistry 2021.0
Modulation of cAMP-Specific PDE without Emetogenic Activity: New Sulfide-Like PDE7 Inhibitors
Journal of Medicinal Chemistry 2014.0
Discovery of Imidazo[1,5-a]pyrido[3,2-e]pyrazines as a New Class of Phosphodiesterase 10A Inhibitiors
Journal of Medicinal Chemistry 2010.0
Fused pyrimidine based inhibitors of phosphodiesterase 7 (PDE7): synthesis and initial structure–activity relationships
Bioorganic & Medicinal Chemistry Letters 2005.0
Novel Pyrazolopyrimidopyridazinones with Potent and Selective Phosphodiesterase 5 (PDE5) Inhibitory Activity as Potential Agents for Treatment of Erectile Dysfunction
Journal of Medicinal Chemistry 2006.0
Neuroprotective efficacy of quinazoline type phosphodiesterase 7 inhibitors in cellular cultures and experimental stroke model
European Journal of Medicinal Chemistry 2012.0
Optimization of N-Phenylpropenoyl-<scp>l</scp>-amino Acids as Potent and Selective Inducible Nitric Oxide Synthase Inhibitors for Parkinson’s Disease
Journal of Medicinal Chemistry 2021.0
(Imidazolylphenyl)pyrrol-2-one inhibitors of cardiac cAMP phosphodiesterase
Journal of Medicinal Chemistry 1993.0
A new therapeutic approach in Parkinson’s disease: Some novel quinazoline derivatives as dual selective phosphodiesterase 1 inhibitors and anti-inflammatory agents
Bioorganic &amp; Medicinal Chemistry 2009.0