Use of substituted aryl-morpholino-, thiomorpholino-or...

Details Use of substituted aryl-morpholino-, thiomorpholino-or... Use of substituted aryl-morpholino-, thiomorpholino-or...

A - Human Necessities

61

K

A61K 31/495 (2006.01) A61K 31/535 (2006.01) A61K 31/54 (2006.01)

Patent

CA 2205530

Disclosed are compounds of formula (I), wherein X is selected from oxygen, sulfur and NR; wherein R is selected from hydrogen, lower alkyl and CH2CH2COAr1; and Z is hydrogen; straight or branched chain alkyl having 1-6 carbon atoms; or Z and R1, R2 or R3 together represent CH2; CH2CH2; CH2O; or CH2S forming a five or six membered ring and such ring may be optionally substituted with lower alkyl or phenyl; R24 is hydrogen; lower alkyl, or optionally substituted phenyl; each R10 is selected from hydrogen and lower alkyl; and Ar1 represents an aryl group or optionally substituted phenyl, thienyl or optionally substituted thienyl; or the pharmaceutically acceptable salts thereof, useful for preventing or decreasing the production of abnormally phosphorylated paired helical filament (PHF) epitopes associated with Alzheimer's Disease and, therefore, useful for treating Alzheimer's Disease.

L'invention porte sur des composés de formule (I) dans lesquels X est choisi parmi oxygène, soufre et NR; R est choisi parmi hydrogène, alkyle inférieur et CH¿2?CH¿2?COAr¿1?; et Z est hydrogène, alkyle à chaine linéaire ou ramifiée contenant 1 à 6 atomes de carbone; ou bien Z et R¿1?, R¿2?, R¿3? représentent ensemble CH¿2?; CH¿2?CH¿2?; CH¿2?O; CH¿2?S formant un cycle à cinq ou six éléments pouvant éventuellement être substitué par un alkyle inférieur ou un phényle; R¿24? est hydrogène, alkyle inférieur ou phényle éventuellement substitué; chacun des R¿10? est choisi parmi hydrogène et alkyle inférieur; et Ar¿1? représente un groupe aryle ou thiényle phényle, éventuellement substitué ou thiényle éventuellement substitué; ou leurs sels pharmaceutiquement acceptables. Ces composés et leurs sels s'avèrent utiles pour prévenir ou réduire la production d'épitopes de filaments en hélice appariés anormalement phosphorylés associés à la maladie d'Alzheimer, et donc utiles pour le traitement de cette maladie.

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