Patent EP-0712627-A2 (EP)
Inventor: GRESE TIMOTHY A
IPC: A61K31/47
Filed: 1995-11-17
Abstract: The present invention provides methods for lowering serum cholesterol comprising administering to a mammal in need of treatment a serum cholesterol lowering amount of a compound of formula I or formula II
       
 wherein 
   R¹ is -H or is a bivalent moiety which distances L from the B-ring by 6-8 intervening atoms; 
   R is -H or selected from the group consisting of hydrogen, a straight or branched, saturated or unsaturated chain having 1-5 carbon atoms, a substituted or unsubstituted cycloalkyl group having 5-7 carbon atoms, a bivalent moiety which joins R³ and L to form a 5- to 7-membered heterocyclic ring, and halo-substituted derivatives of the foregoing; 
   R³ is absent or selected from the group consisting of hydrogen, a straight or branched, saturated or unsaturated chain having 1-5 carbon atoms, a substituted or unsubstituted bivalent moiety which joins R and L to form a 5- to 7-membered heterocyclic ring, and halo-substituted derivatives of the foregoing; 
   R⁴ is hydrogen or lower alkyl; 
   R⁵ and R⁶ each are independently hydrogen, hydroxy, or a moiety which is converted to hydroxy  in vivo ; 
   L is -CON< or -N<; and 
   the dotted line in the B-ring is an optional bond; or a pharmaceutically acceptable salt thereof; and
       
 wherein 
   Q is a moiety having the formula
       
 or  
 
        -R¹-B-R⁷-L-G; 
 
 
    R¹ is absent or is a bivalent moiety which distances L from the B-ring by 6-8 intervening atoms; 
   R is absent or selected from the group consisting of hydrogen, a straight or branched, saturated or unsaturated chain having 1-5 carbon atoms, a substituted or unsubstituted cycloalkyl group having 5-7 carbon atoms, a bivalent moiety which joins R³ and L to form a 5- to 7-membered heterocyclic ring, and halo-substituted derivatives of the foregoing; 
   R³ is absent or selected from the group consisting of hydrogen, a straight or branched, saturated or unsaturated chain having 1-5 carbon atoms, a substituted or unsubstituted bivalent moiety which joins R and L to form a 5- to 7-membered heterocyclic ring, and halo-substituted derivatives of the foregoing; 
   L is -CON< or -N<; 
   B is -O-, -S-, -CH₂-phenyl-O-, -phenyl-O-, or -benzyl-O-; 
   R⁷ is absent or selected from the group consisting of straight- or branched-chain alkylene, straight- or branched-chain alkenylene, phenylene, and fluoro-substituted analogs of the foregoing; 
   G is a moiety which together with L forms a substituted or unsubstituted heterocyclic ring having at least one nitrogen atom or is selected from the group consisting of hydrogen, lower alkyl, lower alkenyl, lower alkynyl, (C₃-C₇)cycloalkyl, halo(lower)alkyl, cyano(lower)alkyl, carboxy(lower)alkyl, (lower)alkoxycarbonyl(lower)alkyl, (C₆-C₁₀)aryl, (C₇-C₁₁)aryl akyl, di(lower)alkylamino(lower)alkyl, and fluoro-substituted analogs of the foregoing; 
   R⁴ is hydrogen or lower alkyl; 
   R⁵ and R⁶ each are independently hydrogen, hydroxy, or a moiety which is converted to hydroxy  in vivo ; 
   Z is -O-, -S-, -CH₂-, -NH-; or -N(CH₃)-; and 
   the dotted line in the B-ring is an optional bond; or a pharmaceutically acceptable salt thereof.