| abstract |
Cholesteryl ester transfer protein inhibitors of the Formula (I) wherein: R1 is Y, W-X or W-Y W is a carbonyl, thiodarbonyl, sulfinyl or sulfnyl X is O-Y, -S-Y, -N(H)-Y or -N-(Y)2. Y is Z or an optionally substituted 1 to 10 membered straight or branched carbon chain where one or two carbon atoms, other than the connecting carbon can be replaced with O, N (or N oxide) or S (or S oxide). Z is 3 to 8 membered carbocyclic or heterocyclic ring or a bicyclic ring system. R2 is an optionally substituted 1 to 6 membered straight or branched carbon chain where one or two carbon atoms other than the connecting carbon can be replaced with O, N (or N oxide) or S (or S oxide) or an optionally substituted carbocyclic or heterocyclic ring which ring ma be optionally be attached via an (C1-C4)alkyl group. Provided that R2 is not methyl. R3 is hydrogen or Q. Q is an optionally substituted 1 to 6 membered straight or branched carbon chain where one carbon atom other than the connecting carbon can be replaced by O, N (or N oxide) or S (or S oxide). In particular Q may be substituted by V. V is a 3 to 8 membered carbocyclic or heterocyclic ring or a bicyclic ring system. R4 is Q1 or V1. Q1 is an optionally substituted 1 to 6 membered straight or branched carbon chain where one carbon atom other than the connecting carbon can be replaced by O, N (or N oxide) or S (or S oxide). V1 is a carbocyclic or heterocyclic ring. Wherein R3 must contain V or R4 must contain V1. R5, R6 , R7 and R8 are each independently hydrogen, a bond, nitro or halo wherein said bond is substituted with T or a 1 to 12 membered straight or branched carbon chain where one or two carbon atoms, other than the connecting carbon can be replaced with O, N (or N oxide) or S (or S oxide). R5 and R6 , or R6 and R7 and/or R7 and R8 may also be taken together and can form at least one optionally substituted 4 to 8 membered ring that is partially saturated or fully unsaturated optionally having 1 to 3 heteroatoms independently selected from nitrogen, sulfur and oxygen. Provided that R1 is not (C1-C6)alkyl. Pharmaceutical compositions containing such inhibitors can be used to elevate certain plasma lipid levels, including high density lipoprotein-cholesterol and to lower certain other plasma lipid levels, such as LDL-cholesterol and triglycerides and in diseases which are exacerbated by low levels of HDL cholesterol and/or high levels of LDL-cholesterol and triglycerides, such as atherosclerosis, cardiovascular diseases, dyslipidemia and vascular complications of diabetes, obesity or endotoxemia in some mammals, including humans. |