Lipid-lowering effects of ethyl 2-phenacyl-3-aryl-1H-pyrrole- 4-carboxylates in rodents.
A series of substituted 2-phenacyl-3-phenyl-1H-pyrrole-4-carboxylates were prepared from substituted acetophenones in 6 steps. The final condensations between a chloroenal and an aminoketone were carried out under neutral conditions in parallel to yield the series listed below. Selected pyrrole derivatives proved to be potent hypolipidemic agents lowering serum triglyceride concentrations in CF-1 male mice after 14 days of I.P. administration. One agent orally lowered serum cholesterol in Sprague-Dawley male rats at 2mg/kg/day after 14 days. The agents demonstrated a lowering of mouse serum LDL- cholesterol levels and selected compounds showed an elevation of serum HDL-cholesterol levels. The cholesterol concentrations in the liver were raised while the cholesterol and triglyceride contents of the aorta were significantly lowered by the selected trisubstituted pyrrole.
Holub
Justin M
JM
Department of Chemistry and Biochemistry, Rider University, 2083 Lawrenceville Rd., Lawrenceville, NJ 08648, USA.
O'Toole-Colin
Kathy
K
Getzel
Adam
A
Argenti
Anthony
A
Evans
Michael A
MA
Smith
Daniel C
DC
Dalglish
Gerard A
GA
Rifat
Shahzad
S
Wilson
Donna L
DL
Taylor
Brett M
BM
Miott
Ulander
U
Glersaye
Josephine
J
Lam
Kam Suet
KS
McCranor
Bryan J
BJ
Berkowitz
Joshua D
JD
Miller
Robert B
RB
Lukens
John R
JR
Krumpe
Keith
K
Gupton
John T
JT
Burnham
Bruce S
BS
D000098:Acetophenones / Q000737:chemistry; D000818:Animals; D000069059:Atorvastatin; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008076:Cholesterol, HDL / Q000097:blood; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D000077340:Fluvastatin; D006538:Heptanoic Acids / Q000737:chemistry; D000960:Hypolipidemic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007211:Indoles / Q000737:chemistry; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D051379:Mice; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000098:Acetophenones; D002264:Carboxylic Acids; D008076:Cholesterol, HDL; D005229:Fatty Acids, Monounsaturated; D006538:Heptanoic Acids; D000960:Hypolipidemic Agents; D007211:Indoles; D008077:Lipoproteins, LDL; D011758:Pyrroles; D000077340:Fluvastatin; D000069059:Atorvastatin