2chm

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
m (Protected "2chm" [edit=sysop:move=sysop])
Line 1: Line 1:
-
[[Image:2chm.png|left|200px]]
+
==CRYSTAL STRUCTURE OF N2 SUBSTITUTED PYRAZOLO PYRIMIDINONES-A FLIPPED BINDING MODE IN PDE5==
 +
<StructureSection load='2chm' size='340' side='right' caption='[[2chm]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[2chm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CHM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2CHM FirstGlance]. <br>
 +
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3P4:5-[2-(BUT-3-EN-1-YLOXY)-5-(1-HYDROXYVINYL)PYRIDIN-3-YL]-3-ETHYL-2-(1-ETHYLAZETIDIN-3-YL)-1,2,6,7A-TETRAHYDRO-7H-PYRAZOLO[4,3-D]PYRIMIDIN-7-ONE'>3P4</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>
 +
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1f0j|1f0j]], [[1jp1|1jp1]], [[1jp2|1jp2]], [[1ro6|1ro6]], [[1ro9|1ro9]], [[1ror|1ror]], [[1rkp|1rkp]], [[1t9r|1t9r]], [[1t9s|1t9s]], [[1tb5|1tb5]], [[1tbf|1tbf]], [[1udt|1udt]], [[1udu|1udu]], [[1uho|1uho]], [[1xlx|1xlx]], [[1xlz|1xlz]], [[1xm4|1xm4]], [[1xm6|1xm6]], [[1xmu|1xmu]], [[1xmy|1xmy]], [[1xn0|1xn0]], [[1xos|1xos]], [[1xot|1xot]], [[1xoz|1xoz]], [[1xp0|1xp0]], [[1y2h|1y2h]], [[1y2j|1y2j]]</td></tr>
 +
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2chm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2chm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2chm RCSB], [http://www.ebi.ac.uk/pdbsum/2chm PDBsum]</span></td></tr>
 +
<table>
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ch/2chm_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Sildenafil (5-[2-ethoxy-5-(4-methyl-1-piperazinylsulfonyl)phenyl]-1-methyl-3-n-propyl -1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one), a potent and selective phosphodiesterase type 5 (PDE5) inhibitor, provided the first oral treatment for male erectile dysfunction. The objective of the work reported in this paper was to combine high levels of PDE5 potency and selectivity with high and dose-independent oral bioavailability, to minimize the impact on the C(max) of any interactions with coadministered drugs in the clinic. This goal was achieved through identification of a lower clearance series with a high absorption profile, by replacing the 5'-piperazine sulfonamide in the sildenafil template with a 5'-methyl ketone. This novel series provided compounds with low metabolism in human hepatocytes, excellent caco-2 flux, and the potential for good aqueous solubility. The in vivo oral and iv pharmacokinetic profiles of example compounds confirmed the high oral bioavailability predicted from these in vitro screens. 5-(5-Acetyl-2-butoxy-3-pyridinyl)-3-ethyl-2-(1-ethyl-3-azetidinyl)-2,6-dih ydro-7H-pyrazolo[4,3-d]pyrimidin-7-one (2) was selected for progression into the clinic.
-
{{STRUCTURE_2chm| PDB=2chm | SCENE= }}
+
A novel series of potent and selective PDE5 inhibitors with potential for high and dose-independent oral bioavailability.,Allerton CM, Barber CG, Beaumont KC, Brown DG, Cole SM, Ellis D, Lane CA, Maw GN, Mount NM, Rawson DJ, Robinson CM, Street SD, Summerhill NW J Med Chem. 2006 Jun 15;49(12):3581-94. PMID:16759100<ref>PMID:16759100</ref>
-
===CRYSTAL STRUCTURE OF N2 SUBSTITUTED PYRAZOLO PYRIMIDINONES-A FLIPPED BINDING MODE IN PDE5===
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
-
{{ABSTRACT_PUBMED_16759100}}
+
==See Also==
-
 
+
*[[Phosphodiesterase|Phosphodiesterase]]
-
==About this Structure==
+
== References ==
-
[[2chm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CHM OCA].
+
<references/>
-
 
+
__TOC__
-
==Reference==
+
</StructureSection>
-
<ref group="xtra">PMID:016759100</ref><references group="xtra"/>
+
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Allerton, C M.N.]]
[[Category: Allerton, C M.N.]]

Revision as of 23:50, 29 September 2014

CRYSTAL STRUCTURE OF N2 SUBSTITUTED PYRAZOLO PYRIMIDINONES-A FLIPPED BINDING MODE IN PDE5

2chm, resolution 1.60Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2chm"
Views
Personal tools
Navigation
Toolbox