3UI7

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

Summary for 3UI7

• Entry DOI: 10.2210/pdb3ui7/pdb
• Descriptor: 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)
• Functional Keywords: inhibitor complex, hydrolase, 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: 78021.10

Authors

Yang, S.,Smotryski, J.,Mcelroy, W.,Ho, G.,Tulshian, D.,Greenlee, W.J.,Hodgson, R.,Xiao, L.,Hruza, A. (deposition date: 2011-11-04, release date: 2011-12-21, Last modification date: 2024-02-28)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.28 Å)