Patent ID: 6313152
Filing Date: 2001-11-06
Classification: A61K

Abstract:
A method for inhibiting .beta.-amyloid peptide release and/or its synthesis in a cell which method comprises administering to such a cell an amount of a compound or a mixture of compounds effective in inhibiting the cellular release and/or synthesis of .beta.-amyloid peptide wherein said compounds are represented by formula I: ##STR11##wherein R.sup.1 is selected from the group consisting of3-pyridyl,4-pyridyl andheteroaryl of 3 to 10 atoms and 1 to 4 heteroatoms selected from oxygen, sulfur and nitrogen wherein the heteroaryl group is optionally substituted with 1 to 3 substituents selected from the group consisting of alkyl, alkoxy, aryl, aryloxy, halo, nitro, thioalkoxy, and thioaryloxy with the proviso that for such heteroaryls when there is at least one nitrogen heteroatom, there is also at least one oxygen and/or sulfur heteroatom;R.sup.2 is selected from the group consisting of hydrogen, alkyl, phenyl, alkylalkoxy, alkylthioalkoxy; andR.sup.3 is selected from the group consisting of --(CH.sub.2).sub.n CR.sup.10 R.sup.5 R.sup.6 wherein n is an integer equal to 0, 1 or 2, R.sup.5 and R.sup.6 are independently selected from hydrogen, alkyl, alkenyl, aryl, heteroaryl, heterocyclic, --NR.sup.7 R.sup.8 where R.sup.7 and R.sup.8 are independently hydrogen or alkyl and --COOR.sup.9 where R.sup.9 is alkyl, and further wherein R.sup.5 and R.sup.6 can be joined to form a cycloalkyl group, a cycloalkenyl group, an aryl group, a heteroaryl group, and a heterocyclic group, and when R.sup.5 and R.sup.6 do not join to form an aryl or heteroaryl group, then R.sup.10 is selected from hydrogen and alkyl with the proviso that when n is zero, then R.sup.10 is hydrogen and when n is greater than zero and R.sup.5 and R.sup.6 are joined to form an aryl or heteroaryl group, then R.sup.10 becomes a bond within that group;X is oxygen or sulfur;X' is hydrogen, hydroxy or fluoro;X"" is hydrogen, hydroxy or fluoro, or X' and X"" together form an oxo group, and pharmaceutically acceptable salts thereof with the provisos that:when R.sup.1 is pyrid-3-yl, R.sup.2 is ethyl, X is oxygen, and X' and X"" are hydrogen, then R.sup.3 is not --CH.sub.2 CH(CH.sub.3).sub.2, andwhen R.sup.1 is indoxazin-3-yl, 2,4-dimethylthiazol-5-yl, or 4-methyl-1,2,5-thiooxadizol-3-yl, R.sup.2 is methyl, X is oxygen, and X' and X"" are hydrogen, then R.sup.3 is not --CH.sub.2 CH(CH.sub.3).sub.2.