1-(3-heteroarylpropyl- or -prop-2-enyl)-4-benzylpiperidines used as NMDA receptor antagonists
AssigneeMerck Patent GmbH
InventorsHelmut Prücher, Joachim Leibrock, Andrew Barber, Gerd Bartoszyk
Life of this patent
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Abstract
Piperidine derivatives of the formula I and their physiologically acceptable salts in which X, Y, Z, R1, R2, R3 and R4 are as defined in claim 1 can be as excitatory amino acid antagonists for combating neurodegenerative disorders including cerebrovascular diseases, epilepsy, schizophrenia, Alzheimer's disease, Parkinson's disease and Huntington's disease, cerebral ischaemias, infarcts and psychosis.
Claims8
A compound which is
- a) 6-{3-[4-(4-fluorobenzyl)piperid-1-yl]propenyl}-3H-benzoxazol-2-one;
- b) 6-{3-[4-(4-fluorobenzyl)piperid-1-yl]propyl}-3H-benzoxazol-2-one;
- c) 6-{3-[4-(4-fluorobenzyl)piperid-1-yl]propenyl}-3H-benzothiazol-2-one;
- d) 5-{3-[4-(4-fluorobenzyl)piperid-1-yl]propenyl}-1,3-benzimidazol-2-one or
- e) 5-{3-[4-(4-fluorobenzyl)piperid-1-yl]propenyl}-1,3-dihydroindol-2-one.
A process for preparing 6-{3-[4-(4-fluorobenzyl)piperid-1-yl]propenyl}-3H-benzoxazol-2-one, 6-{3-[4-(4-fluorobenzyl)piperid-1yl]propyl}-3H-benzoxazol-2-one, 6-{3-[4-(4-fluorobenzyl)piperid-1-yl]propenyl}-3H-benzothiazol-2-one, 5-{3-[4-(4-fluorobenzyl)piperid-1-yl]prophenyl}-1,3-benzimidazol-2-one or 5-{3-[4-(4-fluorobenzyl)piperid-1-yl]propenyl}-1,3-dihydroindol-2-one, or a salt thereof, comprising
- a) reacting a compound of the formula II
- in which
- L is Cl, Br, I, OH or a reactively esterified OH group, and
- R1, R2 and R3 are H
- X is O, N, CH, or S,
- Y is CH,
- Z is CH, or
- Y and Z together are alternatively C═C
- with a compound of the formula III
- in which R4 is F, and is in the 4 position. or
- b) hydrogenating a compound of formula I
- in which
- X is O, N, CH, or S,
- Y and Z together are C═C
- R1, R2 and R3 are H,
- R4 is F, and is in the 4 position, or
- c) eliminating water or L′H from a compound of formula
- in which
- R1 is OH or L′, in which L′ is Cl, Br, I, or a reactively esterified OH group,
- R2 and R3 are H,
- R4 is F, and is in the 4 position,
- X is O, N, CH, or S,
- Y is CH, and
- Z is CH, and/or
- d) converting 6-{3-[4-(4-fluorobenzyl)piperid-1-yl]propenyl}-3H-benzoxazol-2-one, 6-{3-[4-(4-fluorobenzyl)piperid-1-yl]propyl}-3H-benzoxazol-2-one, 6-{3-[4-(4-fluorobenzyl)piperid-1-yl]propenyl}-3H-benzothiazol-2-one, 5-{3-[4-(4-fluorobenzyl)piperid-1-yl]propenyl}-1,3-benzimidazol-2-one, or 5-{3-[4-(4-fluorobenzyl)piperid-1-yl]propenyl}-1,3-dihydroindol-2-one, by treatment with an acid into one of its salts.
Dependencies are inferred from the claim text.