3UUO

The discovery of potent, selectivity, and orally bioavailable pyrozoloquinolines as PDE10 inhibitors for the treatment of Schizophrenia

3UUO の概要

• エントリーDOI: 10.2210/pdb3uuo/pdb
• 分子名称: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A, 6-methoxy-3,8-dimethyl-4-(piperazin-1-yl)-1H-pyrazolo[3,4-b]quinoline, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: inhibitor complex, hydrolase, 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: 79007.96

構造登録者

Ho, G.D.,Yang, S.,Smotryski, J.,Bercovici, A.,Nechuta, T.,Smith, E.M.,McElroy, W.,Tan, Z.,Tulshian, D.,Mckittrick, B.,Greenlee, W.J.,Hruza, A.,Xiao, L.,Rindgen, D.,Guzzi, M.,Zhang, X.,Bleickardt, C.,Mullins, D.,Hodgson, R. (登録日: 2011-11-28, 公開日: 2012-01-25, 最終更新日: 2024-02-28)

主引用文献

Ho, G.D.,Yang, S.W.,Smotryski, J.,Bercovici, A.,Nechuta, T.,Smith, E.M.,McElroy, W.,Tan, Z.,Tulshian, D.,McKittrick, B.,Greenlee, W.J.,Hruza, A.,Xiao, L.,Rindgen, D.,Mullins, D.,Guzzi, M.,Zhang, X.,Bleickardt, C.,Hodgson, R.
The discovery of potent, selective, and orally active pyrazoloquinolines as PDE10A inhibitors for the treatment of Schizophrenia.
Bioorg.Med.Chem.Lett., 22:1019-1022, 2012

PubMed Abstract: High-throughput screening identified a series of pyrazoloquinolines as PDE10A inhibitors. The SAR development led to the discovery of compound 27 as a potent, selective, and orally active PDE10A inhibitor. Compound 27 inhibits MK-801 induced hyperactivity at 3mg/kg with an ED(50) of 4mg/kg and displays a ∼6-fold separation between the ED(50) for inhibition of MK-801 induced hyperactivity and hypolocomotion in rats.

PubMed: 22222034
DOI: 10.1016/j.bmcl.2011.11.127

実験手法

X-RAY DIFFRACTION (2.11 Å)