3bgl

From Proteopedia

---

Revision as of 09:03, 31 January 2008

proteopedia linkproteopedia link

spinqualitylabelsall models 3bgl, resolution 2.225Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Hepatoselectivity of Statins: Design and synthesis of 4-sulfamoyl pyrroles as HMG-CoA reductase inhibitors

Overview

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.

About this Structure

3BGL is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Hydroxymethylglutaryl-CoA reductase (NADPH), with EC number 1.1.1.34 Known structural/functional Sites: , , and . Full crystallographic information is available from OCA.

Reference

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:18155906

Page seeded by OCA on Thu Jan 31 11:03:36 2008