Biological reagents and methods for determining the mechanism in the generation of β-amyloid peptide

An intermediate useful in the preparation of biological reagents that inhibit β-amyloid peptide release and/or its synthesis, wherein said intermediate is represented by formula VI

• A—B′ VI
• wherein A is represented by formula V
• wherein
• R41 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, substituted alkyl, substituted alkenyl, substituted alkynyl, aryl, heteroaryl and heterocyclic;
• R42 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, aryl, heteroaryl and heterocyclic;
• each R43 is independently selected from the group consisting of hydrogen and methyl and R43 together with R44 can be fused to form a cyclic structure of from 3 to 8 atoms which is optionally fused with an aryl or heteroaryl group;
• each R44 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocyclic, substituted alkyl, substituted alkenyl and substituted alkynyl;
• each R45 is selected from hydrogen and methyl or together with R43 forms a cycloalkyl group of from 3 to 6 carbon atoms;
• X is selected from oxygen, sulfur and NH;
• X′ is hydrogen, hydroxy or fluoro;
• and
• X″ is hydrogen, hydroxy or fluoro, or X′ and X″ together form an oxo group;
• Z is selected from the group consisting of a bond covalently linking R41 to —CX′X″—, oxygen and sulfur;
• n is an integer equal to 1 to 3;
• and
• B′ is selected from the group consisting of
• a) (CH2CH(R)Q)nH
• b) alkylene-Q—H
• c) substituted alkylene-Q—H
• wherein R is selected from hydrogen, alkyl or aryl and Q is selected from the group consisting of —O—, —S— and —NH—.