Lipid-Lowering Effects of Ethyl 2-Phenacyl-3-aryl-1H-pyrrole- 4-carboxylates in Rodents

Abstract

-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 LDLcholesterol 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.

Pharmacological cholesterol lowering reverses fibrotic NASH in obese, diabetic mice with metabolic syndrome

“…The dose of ezetimibe used here (5 mg/kg/day) is at the lower end of the range (5-20 mg/kg/day) used by others [21,23]. Likewise, we used a dose of atorvastatin (20 mg/kg/day) that is relatively conservative for mice (others used 8, 20, or 30 mg/kg/day [24][25][26]), noting hepatic drug clearance is $10-fold higher in rodents than in humans.…”

Synthesis and Pharmacological Activities of Amine-Boranes

“…For example, Compactin, which after administration inhibited HMG-CoA reductase activity and thus decreased cholesterol biosynthesis, also inhibited DNA synthesis and growth of cultured mouse L 929 cells [63]. Also, 2,3-dihydrophthalazine-l,4-diones [64], sesquiterpene lactones [65], 1,2,4-triazolidine-3,5-diones [66] and 2,3,4-trisubstituted pyrroles [67] have demonstrated such crossover between cytotoxic and hypolipidemic properties.…”

One‐Pot Four‐Component Synthesis of Tetrasubstituted Pyrroles

“…s, NH). 13 C-NMR: 9.6 (Me); 10.1 (Me); 28.3 (3 Me); 28.4 (3 Me); 80.7 (C); 81.2 (C); 116.9 (C(4)); 119.9 (C(2)); 122.7 (C(3)); 128.6 (C(5)); 160.0 (C(2)ÀCO); 164.9 (C(3)ÀCO). EI-MS: 295 (3), 240 (2), 183 (21) …”

“…In the 1 H-NMR spectrum, the NH proton signal (exchangeable with D 2 O) was visible at 9.67 ppm, and two MeO groups were discernible at 3.79 and 3.83 ppm. The 13 C-NMR signals for the C¼O C-atoms appeared at 161.0 and 166.3 ppm, corresponding to those of the esters.…”