4b72: Difference between revisions
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<StructureSection load='4b72' size='340' side='right'caption='[[4b72]], [[Resolution|resolution]] 1.60Å' scene=''> | <StructureSection load='4b72' size='340' side='right'caption='[[4b72]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4b72]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[4b72]] is a 1 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=4B72 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4B72 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2FB:(6R)-6-(4-METHOXYPHENYL)-2-METHYL-6-(3-PYRIMIDIN-5-YLPHENYL)PYRROLO[3,4-D][1,3]THIAZOL-4-AMINE'>2FB</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4b72 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b72 OCA], [https://pdbe.org/4b72 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4b72 RCSB], [https://www.ebi.ac.uk/pdbsum/4b72 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4b72 ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4b72 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b72 OCA], [https://pdbe.org/4b72 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4b72 RCSB], [https://www.ebi.ac.uk/pdbsum/4b72 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4b72 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Berg S]] | |||
[[Category: Berg | [[Category: Blid J]] | ||
[[Category: Blid | [[Category: Eketjall S]] | ||
[[Category: Eketjall | [[Category: Falting J]] | ||
[[Category: Falting | [[Category: Ginman T]] | ||
[[Category: Ginman | [[Category: Gravenfors Y]] | ||
[[Category: Gravenfors | [[Category: Janson J]] | ||
[[Category: Janson | [[Category: Jeppsson F]] | ||
[[Category: Jeppsson | [[Category: Johansson P]] | ||
[[Category: Johansson | [[Category: Karlstrom S]] | ||
[[Category: Karlstrom | [[Category: Kieseritzky F]] | ||
[[Category: Kieseritzky | [[Category: Kihlstrom J]] | ||
[[Category: Kihlstrom | [[Category: Kolmodin K]] | ||
[[Category: Kolmodin | [[Category: Lindstrom J]] | ||
[[Category: Lindstrom | [[Category: Olsson L]] | ||
[[Category: Olsson | [[Category: Rahm F]] | ||
[[Category: Rahm | [[Category: Slivo C]] | ||
[[Category: Slivo | [[Category: Stromberg K]] | ||
[[Category: Stromberg | [[Category: Swahn B]] | ||
[[Category: Swahn | [[Category: Viklund J]] | ||
[[Category: Viklund | |||
Latest revision as of 05:42, 21 November 2024
Aminoimidazoles as BACE-1 Inhibitors: From De Novo Design to Ab- lowering in BrainAminoimidazoles as BACE-1 Inhibitors: From De Novo Design to Ab- lowering in Brain
Structural highlights
Publication Abstract from PubMedBy use of iterative design aided by predictive models for target affinity, brain permeability, and hERG activity, novel and diverse compounds based on cyclic amidine and guanidine cores were synthesized with the goal of finding BACE-1 inhibitors as a treatment for Alzheimer's disease. Since synthesis feasibility had low priority in the design of the cores, an extensive synthesis effort was needed to make the relevant compounds. Syntheses of these compounds are reported, together with physicochemical properties and structure-activity relationships based on in vitro data. Four crystal structures of diverse amidines binding in the active site are deposited and discussed. Inhibitors of BACE-1 with 3 muM to 32 nM potencies in cells are shown, together with data on in vivo brain exposure levels for four compounds. The results presented show the importance of the core structure for the profile of the final compounds. Core Refinement toward Permeable beta-Secretase (BACE-1) Inhibitors with Low hERG Activity.,Ginman T, Viklund J, Malmstrom J, Blid J, Emond R, Forsblom R, Johansson A, Kers A, Lake F, Sehgelmeble F, Sterky KJ, Bergh M, Lindgren A, Johansson P, Jeppsson F, Falting J, Gravenfors Y, Rahm F J Med Chem. 2013 Jun 13;56(11):4181-205. doi: 10.1021/jm3011349. Epub 2013 May, 20. PMID:23126626[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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