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
Discovery and development of statins 2 statins. One of the main differences between the type 1 and type 2 statins is the replacement of the butyryl group of type 1 statins by the fluorophenyl group of type 2 statins. This group is responsible for additional polar interactions that causes tighter binding to the HMGR enzyme. Statins that belong to this group are: Lovastatin is derived from a fungus source and simvastatin and pravastatin are chemical modifications of lovastatin and as a result do not differ much in structure from lovastatin. All three are partially reduced napthylene ring structures. Simvastatin and lovastatin are inactive lactones which