A series of 22-hydroxycholestero1 derivatives with a modified side chain terminus was prepared. These agents were evaluated in vitro and in vivo for their ability to suppress HMG CoA reductase, the rate-limiting enzyme of cholesterol biosynthesis. In tissue culture assays, 22-hydroxycholestero1 as well as the side chain modified analogues were potent inhibitors of HMG CoA reductase. However, only those sterols with a modified side chain terminus ...