4DFF

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

4DFF の概要

• エントリーDOI: 10.2210/pdb4dff/pdb
• 分子名称: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A, MAGNESIUM ION, ZINC ION, ... (5 entities in total)
• 機能のキーワード: zn binding, mg binding, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q9Y233
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 81487.75

構造登録者

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. (登録日: 2012-01-23, 公開日: 2012-03-14, 最終更新日: 2024-10-30)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.11 Å)