3UI7

Discovery of orally active pyrazoloquinoline as a potent PDE10 inhibitor for the management of schizophrenia

3UI7 の概要

• エントリーDOI: 10.2210/pdb3ui7/pdb
• 分子名称: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A, 6-methoxy-3,8-dimethyl-4-(morpholin-4-ylmethyl)-1H-pyrazolo[3,4-b]quinoline, MAGNESIUM ION, ... (5 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: 78021.10

構造登録者

Yang, S.,Smotryski, J.,Mcelroy, W.,Ho, G.,Tulshian, D.,Greenlee, W.J.,Hodgson, R.,Xiao, L.,Hruza, A. (登録日: 2011-11-04, 公開日: 2011-12-21, 最終更新日: 2024-02-28)

主引用文献

Yang, S.W.,Smotryski, J.,McElroy, W.T.,Tan, Z.,Ho, G.,Tulshian, D.,Greenlee, W.J.,Guzzi, M.,Zhang, X.,Mullins, D.,Xiao, L.,Hruza, A.,Chan, T.M.,Rindgen, D.,Bleickardt, C.,Hodgson, R.
Discovery of orally active pyrazoloquinolines as potent PDE10 inhibitors for the management of schizophrenia.
Bioorg.Med.Chem.Lett., 22:235-239, 2012

PubMed Abstract: A series of pyrazoloquinoline analogs have been synthesized and shown to bind to PDE10 with high affinity. From the SAR study and our lead optimization efforts, compounds 16 and 27 were found to possess potent oral antipsychotic activity in the MK-801 induced hyperactive rat model.

PubMed: 22142545
DOI: 10.1016/j.bmcl.2011.11.023

実験手法

X-RAY DIFFRACTION (2.28 Å)