| Autor: |
Pfefferkorn JA; Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, Michigan 48105, USA. jeffrey.a.pfefferkorn@pfizer.com, 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 |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 2008 Jan 10; Vol. 51 (1), pp. 31-45. Date of Electronic Publication: 2007 Dec 12. |
| DOI: |
10.1021/jm070849r |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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