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    • 23. 发明专利
    • 7-(2H-PYRAZOL-3-YL)-3,5-DIHYDROXY-HEPTANOIC ACID DERIVATIVES AS HMG CO-A REDUCTASE INHIBITORS FOR THE TREATMENT OF LIPIDEMIA
    • CA2590533C
    • 2010-09-07
    • CA2590533
    • 2005-11-14
    • WARNER LAMBERT CO
    • CHOI CHULHOHUTCHINGS RICHARD HPFEFFERKORN JEFFREY ABOWLES DANIEL MERRITTPARK WILLIAM KEUN CHAN
    • C07D231/14A61P3/06A61P3/10C07D405/06
    • The present invention provides compounds of the formula (I), (IV) and (V) and intermediates of the formuale (VI) and (VII): (I), (IV), (V), (VI), (VII). wherein: R1 is hydrogen, halogen, C1-C7 alkyl, C3-C8 cycloalkyl, aryl, aralkyl, heteroaryt, or heteroaralkyl; more specifically, R1 is C1-C7 alkyl or C3-C8 cycloalkyl; even more specifically, R1 is isopropyl; where alkyl, cycloalkyt, aryl, aralkyt, heteroaryl, or heteroaralkyl of R1 is optionally substituted, R2 is hydrogen, halogen, C1-C7 alkyl, C3-C8 cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, NC-, R2bR2aNCO(CH2)n -, R2bR2a NS(O)n-, R2cS(O)n-, R2bR2a N(CH2)n-, R2b-J-C(O)NR2a(CH2)n-, R2b-J-~SO2NR2a(CH2)n-, R2b-J-SONR2a(CH2)n, R7OOC(CH2)n-, or R7CO(CH2)n-; more specifically, R2 is R2bR2aNCO(CH2)n-; even more specifically, R2 is R2bR2a NCO-; where alkyl, cycloalkyl, aryl , aralkyl, heteroaryl, or heteroaralkyl of R2 is optionally substituted, R3 is hydrogen, C1-6 aikyl, C3-6necycloafkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl; more specifically, R3 is aryl; even more specifically, R3 is phenyl or p-fluorophenyl; where alkyl, cycloalkyl, aryl, aralkyl, heteroaryt, or beteroaralkyd of A3 is opltianally substituted and is a bond or is absent. The other substituents are defined in the claims. The present invention relates to compounds and pharmaceutical compositions useful as hypocholesterolemic and hypolipidemic agents. Moree specifically, the present invention concerns certain potent inhibitors of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase ("HMG CoA reciuctase"). The compounds are useful for the treatement of hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, atherosclerosis, Alzheimer's Disease, benign prostatic hypertrophy (BPH), diabetes and osteoporosis.