CHED 1308 |
| As cardiovascular disease moves into the forefront as America's number one killer, drugs such as LipitorŪ (atorvastatin) have grown in sales tremendously. Average sales for LipitorŪ are projected at 12.47 billion for the year 2007 and drugs that possess similar lipid lowering properties have become of high interest. LipitorŪ is a polysubstituted pyrrole that works as a hypolipdemic agent. In addition to its benefits of correcting hyperlipidemias, in some patients it can have toxic effects such as liver damage. In order to further investigate pyrroles as a lipid lowering agent a series of trisubstituted pyrroles were prepared by solution-phase methodologies in six steps. For the synthesis of the pyrroles reactions included Claisen type condensations, [2+3] dipolar cycloadditions and alkylations. The pyrroles were also alkylated or acylated with sodium hydride or PS-TBD, a guanidino-labeled resin and the corresponding alkyl halide or acyl halide. Once pyrroles were synthesized a selection of them were tested for their lipid lowering properties in CF-1 male mice. Mice were administered compounds at 8mg/kg/day by I.P. injections for 14 days before cholesterol and triglyceride content was measured. Previous synthesized compounds have demonstrated successful effects such as lower LDL- cholesterol levels and a select few have even elevated HDL-cholesterol levels. Select compounds illustrated a 56% reduction in serum cholesterol and a 36% reduction in serum triglyceride levels. Many pyrroles were more effective as hypotriglyceridemic agents then the current marketed drug Lipitor (atorvastatin). Herein the synthesis of N- substituted pyrroles and their lipid lowering effects continues to be reported. |
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Undergraduate Research Poster Session: Medicinal Chemistry
2:00 PM-4:00 PM, Monday, April 7, 2008 Morial Convention Center -- Hall A, Poster
Division of Chemical Education |