Functionalized pyrazoles and pyrazolo[3,4-d]pyridazinones: Synthesis and evaluation of their phosphodiesterase 4 inhibitory activity

Add time:07/13/2019    Source:sciencedirect.com

A series of pyrazoles and pyrazolo[3,4-d]pyridazinones were synthesized and evaluated for their PDE4 inhibitory activity. All the pyrazoles were found devoid of activity, whereas some of the novel pyrazolo[3,4-d]pyridazinones showed good activity as PDE4 inhibitors. The most potent compounds in this series showed an IC50 in the nanomolar range. The ability to inhibit TNF-α release in human PBMCs was determined for two representative compounds, finding values in the sub-micromolar range. SARs studies demonstrated that the best arranged groups around the heterocyclic core are 2-chloro-, 2-methyl- and 3-nitrophenyl at position 2, an ethyl ester at position 4 and a small alkyl group at position 6. Molecular modeling studies performed on a representative compound allowed to define its binding mode to the PDE4B isoform.

We also recommend Trading Suppliers and Manufacturers of 6-Ethyl-3-methyl-4-phenyl-6,7-dihydro-2H-pyrazolo[3,4-d]pyridazin-7-one (cas 189307-02-6). Pls Click Website Link as below: cas 189307-02-6 suppliers

Prev:Research on heterocyclic compounds. XXXI. Synthesis and antiinflammatory activity of 2-arylimidazo[1,2-a]pyrazine-3-carboxylic acids
Next:Synthesis and structural characterization of seven copper(I) complexes with 3-amino-5,6-dimethyl-1,2,4-triazine (cas 21134-90-7) and triphenylphosphine/triphenylarsine)