Side chain derivatized 15-oxygenated sterols- methods of using them and a process for preparing them
AuthorSchroepfer, George J., Jr.; Herz, Josef E.; Swaminathan, Shankar; Wilson, William K.
Pharmaceutical compositions are provided for lowering the activity of HMG-CoA reductase and/or lowering serum cholesterol, comprising an amount effective to lower the activity of HMG-CoA reductase and/or lower serum cholesterol of a side chain derivatized 15-oxygenated sterol having the formula (I): ##STR1## the basic ring structure being saturated or unsaturated, wherein R1 is --OH, O, --OR7, ##STR2## a sulfate group, a sugar moiety, or a Mg, Na, or K salt of a sulfate group; R2 is --H, --OH, O, mono- or di-halogen, or a C1 to C6 alkyl group, which may be unsaturated or substituted with halogen; R3 is --H, --OH, halogen, or a C1 to C6 alkyl group, which may be unsaturated or substituted with halogen; R4 is nonexistent when there is a double bond between the 8 and 14 carbons or αH, βH, or an αC1 to C6 alkyl group; R5 is --OH, O, NOH, or ##STR3## R6 is --CH2 CH(CH3)2 or CH2 N(CH3)2, in which one or more of the hydrogen atoms is replaced by OH or halogen; R7 is a C1 to C6 alkyl group; R8 is a C1 to C20 aliphatic group, which may be substituted or unsubstituted, or a phenyl group; and n is an integer of from 2 to 6; andoptionally a pharmaceutically acceptable carrier or excipient, with the proviso that R6 is not --CH2 CH(CH3)(CH2 OH). Methods of using the pharmaceutical compositions containing the side chain derivatized 15-oxygenated sterols are also provided.A new process is also provided for preparing side chain derivatized 15-oxygenated sterols. This process includes oxidative cleavage of the saturated side chain of the sterol with trifluoroperacetic acid to give a side chain trifluoroacetate and subsequent hydrolysis of this ester. The resultant side chain alcohol is a valuable and advanced intermediate for the preparation of side chain derivatives of 15-oxygenated sterols.
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