Structural highlights
Function
[PDE10_HUMAN] Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.[1]
Publication Abstract from PubMed
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.
Discovery of orally active pyrazoloquinolines as potent PDE10 inhibitors for the management of schizophrenia.,Yang SW, Smotryski J, McElroy WT, Tan Z, Ho G, Tulshian D, Greenlee WJ, Guzzi M, Zhang X, Mullins D, Xiao L, Hruza A, Chan TM, Rindgen D, Bleickardt C, Hodgson R Bioorg Med Chem Lett. 2011 Nov 16. PMID:22142545[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wang H, Liu Y, Hou J, Zheng M, Robinson H, Ke H. Structural insight into substrate specificity of phosphodiesterase 10. Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5782-7. Epub 2007 Mar 26. PMID:17389385
- ↑ Yang SW, Smotryski J, McElroy WT, Tan Z, Ho G, Tulshian D, Greenlee WJ, Guzzi M, Zhang X, Mullins D, Xiao L, Hruza A, Chan TM, Rindgen D, Bleickardt C, Hodgson R. Discovery of orally active pyrazoloquinolines as potent PDE10 inhibitors for the management of schizophrenia. Bioorg Med Chem Lett. 2011 Nov 16. PMID:22142545 doi:10.1016/j.bmcl.2011.11.023
