Patent NZ-335598-A (NZ)
Title: 1,2,4-oxadiazoles, processes for their preparation and their use for treating neurogenerative disorders
Inventor: BRENNER MICHAEL
IPC: C07D471/08
Filed: 1997-10-15
Abstract: Oxadiazole derivatives of the general formula (I) for use in the treatment of neurodegenerative disorders and cerebral ischemia. Wherein; X and Y denote oxygen or nitrogen, wherein X and Y cannot both simultaneously be oxygen or nitrogen; Z denotes a group of Formula (II); S1 denotes the Formula (III); wherein V represents oxygen, sulphur or NR7 and B and D, which may be identical or different, denote a C1-4alkylene, C2-4alkenylene or C2-4alkynylene bridge, which may be substituted by =O, -OR7, phenyl or halogen; U represents C3-6cycloalkyl or phenyl group which may be substituted by C1-4alkyl, OR7, C6-10aryl or halogen; E denotes oxygen, sulphur or NR7 (with n,m=1,2 or 3 and n+m>2), and the group is optionally substituted by halogen, =O, OR7, or one or more C1-4alkyl groups; W may be a group of the Formula (IV) optionally substituted by halogen, =O, -OR7, -OCOR7, C1-4alkyl, C2-6alkenyl or C2-6alkynyl, wherein E denotes oxygen or NR7 and n, m, I may be 0, 1 or 2, or W is a C-linked 5- or 6-membered heterocyclic group which contains one or more heteroatoms from the group comprising nitrogen, oxygen or sulphur and may optionally be substituted by benzyl or C1-4alkyl; S2 denotes the Formula (V); S4 denotes the Formula (VI); Q denotes a fused-on, mono- or polyunsaturated 5- or 6-membered heterocyclic ring which may contain one or more heteroatoms from the group comprising oxygen, nitrogen or sulphur, and may optionally be substituted by OR7, NR5R6, halogen, CN, nitro, CF3, COOR7, C1-4alkyl, C2-4alkenyl or C2-4alkynyl; S5 denotes the Formula (VII); R1 denotes benzyl or phenyl, wherein the phenyl ring may optionally be mono- or polysubstituted by one or more of the following groups: fluorine, chlorine or bromine, C1-4alkyl, -CF3, -CR7=NOR7, -NMe2, Net2, -NO2 or -OR7; phenyl further substituted by -V-D-R4, a C- or N-linked 5 or 6-membered heterocycle which contains one or more heteroatoms from the group comprising nitrogen, oxygen or sulphur and may optionally be mono- or polysubstituted by benzyl, methyl, fluorine, chlorine, bromine or hydroxy; cyclopropyl, cyclopentyl or cyclohexyl, which is optionally substituted by =O or -OR7; norbornane, norbornene, dicyclopropylmethyl, adamantine or noradamantane, which are optionally substituted by methyl; Formula (VIII); -CH=CH-phenyl, wherein the phenyl ring may be substituted by methoxy or hydroxy; R2 denotes hydrogen, fluorine, chlorine or bromine, C1-4alkoxy, C1-4alkyl or hydroxy; R3 denotes hydrogen; R4 denotes hydroxy, CN or -NR5R6; an N-oxide of Formula (IX); R5 denotes hydrogen, C1-3alkyl, benzyl or phenyl; R6 denotes hydrogen, C1-3alkyl, benzyl or phenyl; or R5 and R6 together with the nitrogen atom form a saturated or unsaturated 5- or 6-membered ring, which may contain, as further heteroatoms, nitrogen, or oxygen, wherein the heterocycle may be mono- or polysubstituted by methyl; R7 denotes hydrogen, C1-4alkyl, a benzyl or phenyl group, wherein the phenyl ring is optionally mono- or polysubstituted by OH or OCH3;