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US 2004/0106650 A1Published application
4-Pyrrolidino-phenyl-benzyl ether derivatives
AssigneeHoffmann-La Roche Inc.
InventorsHans Iding, Synese Jolidon, Daniela Krummenacher, Rosa Maria Rodriguez-Sarmiento, Andrew William Thomas, Beat Wirz, Wolfgang Wostl, Rene Wyler
Life of this patent
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Abstract
The invention relates to racemic or enantiomerically pure 4-pyrrolidino derivatives, processes for their preparation, pharmaceutical compositions comprising said derivatives, and their use in the prevention and treatment of illness, in particular which is mediated by monoamine oxidase B inhibitors, in particular Alzheimer's disease or senile dementia.
Claims53
A compound of the formula I
- 17
- wherein
- Q is ═N— or ═C(R24)—;
- X—Y is —CH2—CH2—, —CH═CH— or —CH2—O—;
- R1, R1.1 and R1.2 independently from each other are selected from the group consisting of hydrogen, halogen, (C1-C6)-alkyl, halogen-(C1-C6)-alkyl, cyano, (C1-C6)-alkoxy or halogen-(C1-C6)-alkoxy;
- R21, R22 and R23 independently from each other are selected from the group consisting of hydrogen and halogen;
- R24 is hydrogen, halogen or methyl;
- R3 is —C(O)N(H)CH3 or —CH2CN;
- and
- R4 is hydrogen;
- or an individual isomer or racemic or non-racemic mixture thereof.
8 more elements
A compound of the formula I*
- 18
- wherein
- R1 is halogen, halogen-(C1-C6)-alkyl, cyano, (C1-C6)-alkoxy or halogen-(C1-C6)-alkoxy;
- R21, R22, R2′ and R24 independently from each other are selected from the group consisting of hydrogen and halogen;
- R3 is —CONHR5, —CH2CN or —CN;
- R4 is hydrogen;
- R5 is methyl;
- and
- n is 0, 1, 2 or 3;
- as well as individual isomers, racemic or non-racemic mixtures thereof.
7 more elements
A compound selected from the group consisting of
- (RS)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (RS)-[1-[4-(4-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (RS)-1-[4-(3-chloro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (RS)-[1-[4-(3,4-difluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (RS)-[1-[4-(2,6-difluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (RS)-5-oxo-1-[4-(2,4,6-trifluoro-benzyloxy)-phenyl]-pyrrolidine-3-carboxylic acid methylamide,
- (RS)-5-oxo-1-[4-(2,4,5-trifluoro-benzyloxy)-phenyl]-pyrrolidine-3-carboxylic acid methylamide,
- (RS)-5-oxo-1-[4-(2,3,6-trifluoro-benzyloxy)-phenyl]-pyrrolidine-3-carboxylic acid methylamide,
- (RS)-5-oxo-1-[4-(2,3,4-trifluoro-benzyloxy)-phenyl]-pyrrolidine-3-carboxylic acid methylamide, and
- (RS)-5-oxo-1-[4-(3,4,5-trifluoro-benzyloxy)-phenyl]-pyrrolidine-3-carboxylic acid methylamide.
7 more elements
A compound selected from the group consisting of
- (RS)-1-[4-(5-fluoro-2-methyl-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (RS)-1-[4-(3-methoxy-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (RS)-1-[4-(2-methoxy-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (RS)-5-oxo-1-[4-(3-trifluoromethoxy-benzyloxy)-phenyl]-pyrrolidine-3-carboxylic acid methylamide,
- (RS)-5-oxo-1-[4-(3-trifluoromethyl-benzyloxy)-phenyl]-pyrrolidine-3-carboxylic acid methylamide,
- (RS)-1-[4-(3-cyano-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (RS)-1-[4-(3-fluoro-benzyloxy)-3-methyl-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (RS)-1-[4-(4-fluoro-benzyloxy)-3-methyl-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (RS)-1-[4-(3-chloro-benzyloxy)-3-methyl-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (RS)-1-[3-fluoro-4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (RS)-1-[2-fluoro-4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide, and
- (RS)-1-[2,5-difluoro-4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide.
9 more elements
A compound selected from the group consisting of
- (RS)-1-(4-benzyloxy-phenyl)-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (R)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (R)-1-(4-benzyloxy-phenyl)-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (S)-1-(4-benzyloxy-phenyl)-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (R)-1-[4-(4-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (R)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (R)-1-[4-(3-chloro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide, and
- (R)-1-[4-(2,6-difluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide.
6 more elements
A compound selected from the group consisting of
- (R)-5-oxo-1-[4-(2,4,6-trifluoro-benzyloxy)-phenyl]-pyrrolidine-3-carboxylic acid methylamide,
- (RS)-1-[4-(3,4-difluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidin-3-yl}-acetonitrile,
- (RS)-{1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidin-3-yl}-acetonitrile,
- (RS)-[1-(4-benzyloxy-phenyl)-5-oxo-pyrrolidin-3-yl]-acetonitrile,
- (RS)-(E)-1-{4-[2-(3-fluoro-phenyl)-vinyl]-phenyl}-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (RS)-(E)-1-{4-[2-(4-methoxy-phenyl)-vinyl]-phenyl}-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (RS)-(E)-1-{4-[2-(3-methoxy-phenyl)-vinyl]-phenyl}-5-oxo-pyrrolidine-3-carboxylic acid methylamide, and
- (RS)-(E)-1-{4-[2-(4-fluoro-phenyl)-vinyl]-phenyl}-5-oxo-pyrrolidine-3-carboxylic acid methylamide.
5 more elements
A compound selected from the group consisting of
- (RS)-1-{4-[2-(3-chloro-phenyl)-ethyl]-phenyl}-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (RS)-1-{4-[2-(4-chloro-phenyl)-ethyl]-phenyl}-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (RS)-1-{4-[2-(3-fluoro-phenyl)-ethyl]-phenyl}-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (RS)-1-{4-[2-(4-fluoro-phenyl)-ethyl]-phenyl}-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (RS)-1-{4-[2-(3-methoxy-phenyl)-ethyl]-phenyl}-5-oxo-pyrrolidine-3-carboxylic acid methylamide,
- (RS)-1-[6-(4-fluoro-benzyloxy)-pyridin-3-yl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide, and
- (RS)-1-[4-(2-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide.
4 more elements
A composition comprising a compound of formula I
- 19
- wherein
- Q is ═N— or ═C(R24)—;
- X—Y is —CH2—CH2—, —CH═CH— or —CH2—O—;
- R1, R1.1 and R1.2 independently from each other are selected from the group consisting of hydrogen, halogen, (C1-C6)-alkyl, halogen-(C1-C6)-alkyl, cyano, (C1-C6)-alkoxy or halogen-(C1-C6)-alkoxy;
- R21, R22 and R23 independently from each other are selected from the group consisting of hydrogen and halogen;
- R14 is hydrogen, halogen or methyl;
- R3 is —C(O)N(H)CH3 or —CH2CN;
- and
- R4 is hydrogen;
- or an individual isomer or racemic or non-racemic mixture thereof, and a pharmaceutically acceptable carrier.
8 more elements
A composition comprising a compound of formula I*
- 20
- wherein
- R1 is halogen, halogen-(C1-C6)-alkyl, cyano, (C1-C6)-alkoxy or halogen-(C1-C6)-alkoxy;
- R21, R22, R23 and R24 independently from each other are selected from the group consisting of hydrogen and halogen;
- R3 is —CONHR5, —CH2CN or —CN;
- R4 is hydrogen;
- R5 is methyl;
- and
- n is 0, 1, 2 or 3;
- or an individual isomer or racemic or non-racemic mixture thereof, and a pharmaceutically acceptable carrier.
7 more elements
Dependencies are inferred from the claim text.