Sliskovic D R, Roth B D, Wilson M W, Hoefle M L, Newton R S
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
J Med Chem. 1990 Jan;33(1):31-8. doi: 10.1021/jm00163a006.
A series of 1,3,5-trisubstituted pyrazole mevalonolactones were prepared and evaluated for their ability to inhibit the enzyme HMG-CoA reductase in vitro. Since previous studies suggested that the 5-(4-fluorophenyl) and 3-(1-methylethyl) substituents afforded optimum potency, attention was focused on variations in position 1 of the pyrazole ring. Biological evaluation of analogues bearing a variety of 1-substituents suggested that, although most substituents were tolerated, none afforded an advantage over phenyl, which exhibited potency comparable to that of compactin in vitro.
制备了一系列1,3,5-三取代吡唑甲羟戊酸内酯，并对其体外抑制HMG-CoA还原酶的能力进行了评估。由于先前的研究表明，5-(4-氟苯基)和3-(1-甲基乙基)取代基具有最佳活性，因此重点关注吡唑环1位的变化。对带有各种1-取代基的类似物进行的生物学评估表明，尽管大多数取代基都可耐受，但没有一个取代基比苯基更具优势，苯基在体外表现出与洛伐他汀相当的活性。
