Discovery and development of statins polar methane sulfonamide group, which is quite hydrophilic and confers low lipophilicity. The sulfonamide group forms a unique polar interaction with the enzyme. As a result, rosuvastatin has superior binding affinity to the HMGR enzyme compared to the other statins, which is directly related to its efficiency to lower LDL cholesterol. Lipophilicity of the statins is considered to be quite important since the hepatoselectivity of the statins is related to their lipophilicity. The more lipophilic statins tend to achieve higher levels of exposure in non-hepatic tissues, while the hydrophilic statins tend to be more hepatoselective. The difference in selectivity is
Chronic endothelial injury hypothesis the hypertension often seen with atherosclerosis. The role LDL plays suggests two different approaches to treatment and prevention. The first approach involves discouraging the accumulation of LDL by lowering the levels of serum LDL, an idea more closely associated with the lipid hypothesis. A major breakthrough involved the discovery of statins, a class of drugs which help to clear LDL from the bloodstream. It has been demonstrated conclusively that elevated levels of LDL are associated with higher risk of mortality from coronary heart disease (CHD); it has also been shown that statins substantially lower the risk of mortality in patients