3bgl: Difference between revisions

4-Sulfamoyl pyrroles were designed as novel hepatoselective HMG-CoA, reductase inhibitors (statins) to reduce myalgia, a statin-induced adverse, effect. The compounds were prepared via a [3+2] cycloaddition of a, Munchnone with a sulfonamide-substituted alkyne. We identified compounds, with greater selectivity for hepatocytes compared to L6-myocytes than, rosuvastatin and atorvastatin. There was an inverse correlation of myocyte, potencies and ClogP values. A number of analogs were effective at reducing, cholesterol in acute and chronic in vivo models but they lacked sufficient, chronic in vivo activity to warrant further development.

3BGL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=RID:'>RID</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_reductase_(NADPH) Hydroxymethylglutaryl-CoA reductase (NADPH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.34 1.1.1.34] Known structural/functional Sites: <scene name='pdbsite=AC1:Rid Binding Site For Residue A 2'>AC1</scene>, <scene name='pdbsite=AC2:Rid Binding Site For Residue B 1'>AC2</scene>, <scene name='pdbsite=AC3:Rid Binding Site For Residue C 4'>AC3</scene> and <scene name='pdbsite=AC4:Rid Binding Site For Residue D 3'>AC4</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BGL OCA].  

Hepatoselectivity of statins: Design and synthesis of 4-sulfamoyl pyrroles as HMG-CoA reductase inhibitors., Park WK, Kennedy RM, Larsen SD, Miller S, Roth BD, Song Y, Steinbaugh BA, Sun K, Tait BD, Kowala MC, Trivedi BK, Auerbach B, Askew V, Dillon L, Hanselman JC, Lin Z, Lu GH, Robertson A, Sekerke C, Bioorg Med Chem Lett. 2007 Dec 5;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18155906 18155906]

[[Category: Finzel, B.C.]]

[[Category: Park, W.K.C.]]

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