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==The SAR development of dihydroimidazoisoquinoline derivatives as phosphodiesterase 10A inhibitors for the treatment of schizophrenia== | ==The SAR development of dihydroimidazoisoquinoline derivatives as phosphodiesterase 10A inhibitors for the treatment of schizophrenia== | ||
<StructureSection load='4dff' size='340' side='right' caption='[[4dff]], [[Resolution|resolution]] 2.11Å' scene=''> | <StructureSection load='4dff' size='340' side='right'caption='[[4dff]], [[Resolution|resolution]] 2.11Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4dff]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4dff]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DFF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DFF FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0JP:8,9-DIMETHOXY-1-(1,3-THIAZOL-5-YL)-5,6-DIHYDROIMIDAZO[5,1-A]ISOQUINOLINE'>0JP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.11Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0JP:8,9-DIMETHOXY-1-(1,3-THIAZOL-5-YL)-5,6-DIHYDROIMIDAZO[5,1-A]ISOQUINOLINE'>0JP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4dff FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dff OCA], [https://pdbe.org/4dff PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dff RCSB], [https://www.ebi.ac.uk/pdbsum/4dff PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dff ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/PDE10_HUMAN 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.<ref>PMID:17389385</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 17: | Line 18: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4dff" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Phosphodiesterase|Phosphodiesterase]] | *[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 25: | Line 27: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Bercovici | [[Category: Large Structures]] | ||
[[Category: Bleichardt | [[Category: Bercovici A]] | ||
[[Category: Greenlee | [[Category: Bleichardt C]] | ||
[[Category: Guzzi | [[Category: Greenlee WJ]] | ||
[[Category: Ho | [[Category: Guzzi M]] | ||
[[Category: Hodgson | [[Category: Ho GD]] | ||
[[Category: Hruza | [[Category: Hodgson R]] | ||
[[Category: Mullins | [[Category: Hruza A]] | ||
[[Category: Mullins D]] | |||
[[Category: Rindgen | [[Category: Rindgen D]] | ||
[[Category: Seganish | [[Category: Seganish WM]] | ||
[[Category: Tulshian | [[Category: Tulshian D]] | ||
[[Category: | [[Category: Van Rijn R]] | ||
[[Category: | [[Category: Xiao L]] | ||
[[Category: | [[Category: Zhang X]] | ||
Latest revision as of 12:55, 30 October 2024
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
FunctionPDE10_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 PubMedThe 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. See AlsoReferences
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