4tpp
From Proteopedia
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| - | ''' | + | ==2-(3-alkoxy-1-azetidinyl) quinolines as novel PDE10A inhibitors== |
| + | <StructureSection load='4tpp' size='340' side='right' caption='[[4tpp]], [[Resolution|resolution]] 2.65Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4tpp]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TPP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TPP FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=35D:1-[4-(3-{[1-(QUINOLIN-2-YL)AZETIDIN-3-YL]OXY}QUINOXALIN-2-YL)PIPERIDIN-1-YL]ETHANONE'>35D</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4tpm|4tpm]]</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4tpp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tpp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4tpp RCSB], [http://www.ebi.ac.uk/pdbsum/4tpp PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | We report the discovery of a novel series of 2-(3-alkoxy-1-azetidinyl) quinolines as potent and selective PDE10A inhibitors. Structure-activity studies improved the solubility (pH 7.4) and maintained high PDE10A activity compared to initial lead compound 3, with select compounds demonstrating good oral bioavailability. X-ray crystallographic studies revealed two distinct binding modes to the catalytic site of the PDE10A enzyme. An ex vivo receptor occupancy assay in rats demonstrated that this series of compounds covered the target within the striatum. | ||
| - | + | Synthesis and preliminary biological evaluation of potent and selective 2-(3-alkoxy-1-azetidinyl) quinolines as novel PDE10A inhibitors with improved solubility.,Rzasa RM, Frohn MJ, Andrews KL, Chmait S, Chen N, Clarine JG, Davis C, Eastwood HA, Horne DB, Hu E, Jones AD, Kaller MR, Kunz RK, Miller S, Monenschein H, Nguyen T, Pickrell AJ, Porter A, Reichelt A, Zhao X, Treanor JJ, Allen JR Bioorg Med Chem. 2014 Oct 22;22(23):6570-6585. doi: 10.1016/j.bmc.2014.10.013. PMID:25456383<ref>PMID:25456383</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | == References == | |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Chmait, S]] | ||
| + | [[Category: Hydrolase-hydrolase inhibitor complex]] | ||
| + | [[Category: Phosphodiesterase 10a]] | ||
| + | [[Category: Quinoline]] | ||
Revision as of 12:41, 17 December 2014
2-(3-alkoxy-1-azetidinyl) quinolines as novel PDE10A inhibitors
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