4dff

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

Structural highlights

4dff is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.11Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

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.

The SAR development of dihydroimidazoisoquinoline derivatives as phosphodiesterase 10A inhibitors for the treatment of schizophrenia.,Ho GD, Michael Seganish W, Bercovici A, Tulshian D, Greenlee WJ, Van Rijn R, Hruza A, Xiao L, Rindgen D, Mullins D, Guzzi M, Zhang X, Bleickardt C, Hodgson R Bioorg Med Chem Lett. 2012 Feb 9. PMID:22377514^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Ho GD, Michael Seganish W, Bercovici A, Tulshian D, Greenlee WJ, 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. 2012 Feb 9. PMID:22377514 doi:10.1016/j.bmcl.2012.01.113

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] Ho GD, Michael Seganish W, Bercovici A, Tulshian D, Greenlee WJ, 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. 2012 Feb 9. PMID:22377514 doi:10.1016/j.bmcl.2012.01.113

[1]

[2]