Phosphorus-containing inhibitors of HMG-CoA reductase. 2. Synthesis and biological activities of a series of substituted pyridines containing a hydroxyphosphinyl moiety.
A series of 2,3,4,(5),6-substituted pyridines containing a hydroxyphosphinyl functionally have been prepared and were evaluated for their ability to inhibit the enzyme HMG-CoA reductase. Systematic substitution of both R1-R4 and X-Y led to compounds of type 3-6 with in vitro potency greater than that of mevinolin (Na salt).
Robl
J A
JA
Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000.
Duncan
L A
LA
Pluscec
J
J
Karanewsky
D S
DS
Gordon
E M
EM
Ciosek
C P
CP
Rich
L C
LC
Dehmel
V C
VC
Slusarchyk
D A
DA
Harrity
T W
TW
D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008148:Lovastatin / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D012867:Skin / Q000166:cytology / Q000378:metabolism
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D009943:Organophosphorus Compounds; D011725:Pyridines; D002784:Cholesterol; D008148:Lovastatin