2r4f | pdb_00002r4f

File:2r4f.jpg

Substituted Pyrazoles as Hepatselective HMG-COA reductase inhibitors

Overview

In light of accumulating evidence that aggressive LDL-lowering therapy may offer increased protection against coronary heart disease, we undertook the design and synthesis of a novel series of HMG-CoA reductase inhibitors based upon a substituted pyrazole template. Optimizing this series using both structure-based design and molecular property considerations afforded a class of highly efficacious and hepatoselective inhibitors resulting in the identification of (3 R,5 R)-7-[2-(4-fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2 H-pyrazol-3-yl]-3,5-dihydroxy-heptanoic (PF-3052334) as a candidate for the treatment of hypercholesterolemia.

Disease

Known disease associated with this structure: Statins, attenuated cholesterol lowering by OMIM:[142910]

About this Structure

2R4F is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Substituted pyrazoles as hepatoselective HMG-CoA reductase inhibitors: discovery of (3R,5R)-7-[2-(4-fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2H -pyrazol-3-yl]-3,5-dihydroxyheptanoic acid (PF-3052334) as a candidate for the treatment of hypercholesterolemia., Pfefferkorn JA, Choi C, Larsen SD, Auerbach B, Hutchings R, Park W, Askew V, Dillon L, Hanselman JC, Lin Z, Lu GH, Robertson A, Sekerke C, Harris MS, Pavlovsky A, Bainbridge G, Caspers N, Kowala M, Tait BD, J Med Chem. 2008 Jan 10;51(1):31-45. Epub 2007 Dec 12. PMID:18072721 Page seeded by OCA on Wed Apr 30 13:22:16 2008

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