4DFF

The SAR development of dihydroimidazoisoquinoline derivatives as phosphodiesterase 10A inhibitors for the treatment of schizophrenia

Summary for 4DFF

• Entry DOI: 10.2210/pdb4dff/pdb
• Descriptor: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A, MAGNESIUM ION, ZINC ION, ... (5 entities in total)
• Functional Keywords: zn binding, mg binding, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q9Y233
• Total number of polymer chains: 2
• Total formula weight: 81487.75

Authors

Ho, G.D.,Seganish, W.M.,Bercovici, A.,Tulshian, D.,Greenlee, W.J.,Van Rijn, R.,Hruza, A.,Xiao, L.,Rindgen, D.,Mullins, D.,Guzzi, M.,Zhang, X.,Bleichardt, C.,Hodgson, R. (deposition date: 2012-01-23, release date: 2012-03-14, Last modification date: 2024-10-30)

Primary citation

Ho, G.D.,Michael Seganish, W.,Bercovici, A.,Tulshian, D.,Greenlee, W.J.,Van Rijn, R.,Hruza, A.,Xiao, L.,Rindgen, D.,Mullins, D.,Guzzi, M.,Zhang, X.,Bleickardt, C.,Hodgson, R.
The SAR development of dihydroimidazoisoquinoline derivatives as phosphodiesterase 10A inhibitors for the treatment of schizophrenia.
Bioorg.Med.Chem.Lett., 22:2585-2589, 2012

PubMed Abstract: The identification of potent and orally active dihydroimidazoisoquinolines as PDE 10A inhibitors is reported. The SAR development led to the discovery of compound 35 as a potent, selective, and orally active PDE10A inhibitor. Compound 35 inhibited MK-801-induced hyperactivity at 3mg/kg and displayed a 10-fold separation between the minimal effective doses for inhibition of MK-801-induced hyperactivity and hypolocomotion in rats.

PubMed: 22377514
DOI: 10.1016/j.bmcl.2012.01.113

Experimental method

X-RAY DIFFRACTION (2.11 Å)