Substituted pyrrole derivatives and their use as HMG-Co inhibitors

摘要

Disclosed are substituted pyrrole derivatives of formula I, their pharmaceutically acceptable salts (suitable salts include salts selected from lithium, sodium, potassium, calcium, magnesium, zinc, aluminium, amino acid, ammonium, mono-alkyl ammonium, dialkyl ammonium, trialkyl ammonium and N-methyl glucamine), pharmaceutically acceptable solvates, tautomers, racemates, pure enantiomers, polymorphs, diastereoisomers or N-oxides, which can be used as 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors. Of particular importance is the compound which is (3R,5R)-7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-[(4-hydroxymethylphenylamino)carbonyl]-pyrrol-1-yl]-3,5-dihydroxy-heptanoic acid. Also disclosed is the use of a compound as defined above for the manufacture of a medicament for treatment or prevention of cholesterol-related disease, diabetes and related diseases, cerebrovascular disease or cardiovascular disease, in a mammal (and particularly diseases such arteriosclerosis, atherosclerosis, hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia, hypertriglyceridemia, hypertension, stroke, ischemia, endothellium dysfunctions, peripheral vascular disease, peripheral arterial disease, coronary heart disease, myocardial infarction, cerebral infarction, myocardial microvascular disease, dementia, Alzheimer's disease, osteoporosis and/or osteopenia, angina or restenosis). A process for the preparation of the above compounds is further disclosed.