Selective cholesterol absorption inhibitors

Reyderman L, Kosoglou T, Statkevich P, Pember L, Boutros T, Maxwell SE, Affrime M, Batra V. Assessment of a multiple-dose drug interaction between ezetimibe, a novel selective cholesterol absorption inhibitor and gemfibrozil. International J Clin Pharmacol Ther 2004 42(9) 512-8. 

Nutescu EA, Shapiro NL. Ezetitnibe a selective cholesterol absorption inhibitor. Pharmacotherapy. 2003 23 1463-1474. 

Selective cholesterol absorption inhibitor Inhibitors of fasting-induced lipolysis. 

Patrick, J.E. et al., Disposition of the selective cholesterol absorption inhibitor ezetimibe in healthy male subjects, Drug Metab. Dispos., 30(4), 430, 2002. 

Kosoglou T, Meyer I, Veltri EP, Statkevich P, Yang B, Zhu Y, MellarsL, M nvell SE, Patrick JE, Cutler DL, Batra VK, Aflrime MB. Pharmacodynamic interaction between die new selective cholesterol absorption inhibitor ezetimibe and simvastatin. BrJ Clin Pharmacol (2002) 54, 309-19,... 

Patrick, J.E. Kosoglou, T. Stauber, K.L. Alton, K.B. Maxwell, S.E. Zhu, Y. Statkevich, P. lannucci, R. Chowdhury, S. Affrime, M. Cayen, M.N. Disposition of the selective cholesterol absorption inhibitor ezetimibe in healthy male subjects, Drug Metab.Dispos., 2002, 30, 430-437. 

Monobactams have been investigated as p-lactamase inhibitors <98CHE1308, 98CHE1319>. The ketene-imine route to P-lactams was used to obtain 1,3,4-trisubstituted derivatives with high trans selectivity. The enolate from 4-hydroxy-y-lactone reacted with the imine (Ar CH NAr ) to give 59, vdiich cyclized in the presence of lithium chloride at low temperature to yield 60. The compounds were assayed for cholesterol absorption inhibition and 61 (R = = OH, R = F) was found to be a potent inhibitor of 3-hydroxy-3-... 

Pancreatic cholesterol esterase (3.1.1.3.) aids in transporting cholesterol to the enterocyte. By utilizing a selective and potent cholesterol esterase inhibitor 6-chloro-3-(l-ethyl-2-cyclohexyl)-2-pyrone, the absorption of cholesterol in hamsters could be reduced [71]. Wadkins et al. [72] synthesized novel sulfonamide derivatives, which demonstrated greater than 200-fold selectivity for human intestinal carboxylesterase compared with the human liver carboxylesterase hCEl, and none of them was an inhibitor of human acetylcholinesterase or butyrylcholinester-ase. Maybe these agents can serve as lead compounds for the development of effective, selective carboxylesterase inhibitors for clinical applications. Also the potent P-gp inhibitor verapamil [73] as well as S,S,S-tributylphosphortrithionate (DEF) [74] may exhibit carboxylesterase inhibitory properties. Various other inhibitors of human esterases are listed in Table 5.6. 

Selective cholesterol Reduction of LDL absorption inhibitor cholesterol levels by mp 16S °C inhibiting dietary... 

Ezetimibe (Zetia) is a selective inhibitor of dietary cholesterol absorption. In addition to this decreased cholesterol absorption leads to an increase in LDL-cholesterol uptake into cells, thus decreasing levels in the blood plasma (Rossi S, 2006). 

Catapano AL. Ezetimibe a selective inhibitor of cholesterol absorption. > . Heart J. Suppl. 2001 3(Esuppl) E6-E10. 

Ezetimibe is a selective inhibitor of intestinal absorption of cholesterol and phytosterols. A transport protein, NPC1L1, appears to be the target of the drug. It is effective even in the absence of dietary cholesterol because it inhibits reabsorption of cholesterol excreted in the bile. 

Ezetimibe is a selective potent inhibitor of the intestinal absorption of dietary and biliary cholesterol. A total of 432 patients were included in a pooled analysis of two phase-II studies, both lasting for 12 weeks ezetimibe was well tolerated, with an adverse events profile similar to that of placebo (1). In 668 patients who took ezetimibe with simvastatin, the adverse effects were similar to those with simvastatin alone (2). 

Ezetimibe is a selective inhibitor of the Niemaim-Pick Cl like 1 cholesterol transporter protein, which is expressed on the brush border membrane of the small intestine, and blocks the transport of dietary and biliary cholesterol into the jejunal enterocyte without reducing the absorption of fat-soluble vitamins, TG or bile acids. Ezetimibe may also block the hepatic reabsorption of biliary cholesterol and further augment the elimination of cholesterol. 

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