| Autor: |
Roth BD; Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105., Blankley CJ, Chucholowski AW, Ferguson E, Hoefle ML, Ortwine DF, Newton RS, Sekerke CS, Sliskovic DR, Stratton CD, et. al. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 1991 Jan; Vol. 34 (1), pp. 357-66. |
| DOI: |
10.1021/jm00105a056 |
| Abstrakt: |
A series of trans-tetrahydro-4-hydroxy-6-[2-(2,3,4,5-substituted-1H-pyrrol-1-yl) ethyl]-2H-pyran-2-ones and their dihydroxy acids were prepared and tested for their ability to inhibit the enzyme HMG-CoA reductase in vitro. Inhibitory potency was found to increase substantially when substituents were introduced into positions three and four of the pyrrole ring. A systematic exploration of structure-activity relationships at these two positions led to the identification of a compound ((+)-33,(+)-(4R)-trans-2-(4-fluororphenyl)-5-(1-methylethyl)-N,3- diphenyl-1- [(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-4- carboxamide) with five times the inhibitory potency of the fungal metabolite compactin. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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