Discovery of 4-hydroxy-1,6-naphthyridine-3-carbonitrile derivatives as novel PDE10A inhibitors.

Article Details

Citation

Copy to clipboard

Bauer U, Giordanetto F, Bauer M, O'Mahony G, Johansson KE, Knecht W, Hartleib-Geschwindner J, Carlsson ET, Enroth C

Discovery of 4-hydroxy-1,6-naphthyridine-3-carbonitrile derivatives as novel PDE10A inhibitors.

Bioorg Med Chem Lett. 2012 Mar 1;22(5):1944-8. doi: 10.1016/j.bmcl.2012.01.046. Epub 2012 Jan 26.

PubMed ID

22321214 [ View in PubMed

]

Abstract

A series of 1,6-naphthyridine-based compounds was synthesized as potent phosphodiesterase 10A (PDE10A) inhibitors. Structure-based chemical modifications of the discovered chemotype served to further improve potency and selectivity over DHODH, laying the foundation for future optimization efforts.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
4,5-bis(4-methoxyphenyl)-2-thiophen-2-yl-1H-imidazole	cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A	IC 50 (nM)	35	N/A	N/A	Details
Papaverine	cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A	IC 50 (nM)	36	N/A	N/A	Details