| 摘要 |
A compound has the formula A-B-D wherein: A is a group of formula (2); R1, R2, R5 and R6 are independently optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocyclic; Z is -CX'X"C(O)-, -T-CH2-C(O)-, -T-C(O)-C(O)- or -CX'X"-T-C(O)-; X' and X" are independently hydrogen, hydroxy or fluoro, or X' and X" together form an oxo group; T is oxygen, sulphur or -NR3; R3 is hydrogen, acyl, alkyl, aryl or heteroaryl group; m and p are independently is 0 or 1; T' is a bond covalently linking R' to -CX'X"-, oxygen, sulphur or -NR3; W and X are independently -(CR7R7)q-, oxygen, sulphur or -NR8; q is 1 or 2; each R7 and R8 is independently hydrogen, optionally substituted alkyl, cycloalkyl, aryl, heteroaryl, acyl, acyloxy, carboxyl, carboxyl esters or heterocyclic and further, when q is 2, an R7 group on each of the carbon atoms can optionally be fused to form an aryl, heteroaryl, heterocyclic or cycloalkyl group with the ethylene group with the proviso that when unsaturated, the remaining R7 group on each carbon atom participates in the unsaturation; R4 is hydrogen, optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocyclic; B is (i) -C(O)-N(H)-CH(R5) or a group of formula 3 or when A is either formula (ii) or (iii) as defined above, then B can also be a covalent bond linking A to D; D is (i) -C(O)Y, (ii) -C(S)Y or (iii) a group of formula 4; Y is optionally substituted alkyl, alkoxy, thioalkoxy or is cycloalkyl, hydroxy, aryl, heteroaryl, heterocyclic, -NR'R", -NHSO2-R8, -NR9NR10R10, -ONR9[C(O)O]zR10, -CR11R11Y' R' and R" are independently hydrogen, optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl or heterocyclic provided that one of R' or R" is hydroxy or alkoxy, or R' and R" are joined to form an optionally substituted cyclic group optionally containing 1 to 2 additional heteroatoms of oxygen, sulphur or nitrogen; R9 is hydrogen or alkyl; each R10 and R11 is independently hydrogen, optionally substituted alkyl, alkenyl, cycloalkyl, aryl, heteroaryl or heterocyclic; z is 0 or 1; Y' is hydroxyl, amino, thiol, optionally substituted alkoxy or thioalkoxy, -OC(O)R9, -SSR9 or -SSC(O)R9; A*, together with -C=N-, forms a heterocyclic group which is optionally fused to form a bi- or multi-fused ring system with one or more ring structures selected from optionally substituted cycloalkyl, cycloalkenyl, heterocyclic, aryl or heteroaryl group limited by the provisos listed in the specification. A pharmaceutical composition thereof is useful for inhibiting the cellular release and/or synthesis of b-amyloid peptide, preventing the onset of Alzheimer's disease or inhibiting further deterioration in the condition.
|
