title: Phosphorus-containing inhibitors of HMG-CoA reductase. 2. Synthesis and biological activities of a series of substituted pyridines containing a hydroxyphosphinyl moiety.
abstract: 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).
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000.
authors.forename: J A
authors.initials: JA
authors.lastname: Robl
authors.forename: L A
authors.initials: LA
authors.lastname: Duncan
authors.forename: J
authors.initials: J
authors.lastname: Pluscec
authors.forename: D S
authors.initials: DS
authors.lastname: Karanewsky
authors.forename: E M
authors.initials: EM
authors.lastname: Gordon
authors.forename: C P
authors.initials: CP
authors.lastname: Ciosek
authors.forename: L C
authors.initials: LC
authors.lastname: Rich
authors.forename: V C
authors.initials: VC
authors.lastname: Dehmel
authors.forename: D A
authors.initials: DA
authors.lastname: Slusarchyk
authors.forename: T W
authors.initials: TW
authors.lastname: Harrity
mesh_terms: 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
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D009943:Organophosphorus Compounds; D011725:Pyridines; D002784:Cholesterol; D008148:Lovastatin