Journal of Medicinal Chemistry p. 367 - 373 (1991)
Update date:2022-07-29
Topics:
Sliskovic, D. R.
Picard, J. A.
Roark, W. H.
Roth, B. D.
Ferguson, E.
et al.
A series of substituted quinoline mevalonolactones were prepared and evaluated for their ability to inhibit the enzyme HMG-CoA reductase both in vitro and (cholesterol biosynthesis) in vivo.Since previous studies suggested that the 4-(4-fluorophenyl) and 2-(1-methylethyl) substituents afforded optimum potency, attention was focused on variations at position 6 of the quinoline ring.Biological evaluation of a small number of analogues bearing a variety of 6-substituents showed that modification at this position had little effect on potency.Several compounds (8b, 8e, and 11) were identified that showed comparable potency to compaction and mevinolin in both the in vitro and in vivo assays.
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