Benzyloxy derivatives as MAOB inhibitors
AssigneeHoffman-La Roche Inc.
InventorsSynese Jolidon, Rosa Maria Rodriguez-Sarmiento, Andrew William Thomas, Wolfgang Wostl, Rene Wyler
Life of this patent
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Abstract
The invention relates to compounds of the formula and their pharmaceutically acceptable salts wherein R1, R2, R3, R4, R5, n, m, and o are as defined in the specification. The compounds are selective monoamine oxidase β inhibitors and are useful for the treatment and prevention of Alzheimer's disease and senile dementia, as well as other CNS disorders. The invention also relates to processes for preparing such compounds and pharmaceutical compositions containing them.
Claims17
A compound of the formula
- wherein
- R1 and R2 are each independently hydrogen or C1-C6-alkyl;
- R3 and R4 are each independently hydrogen or C1-C6-alkyl;
- R5 is CN, (C1-C6)-alkyl or (C1-C6)-alkoxy;
- and
- n is 1 or 2;
- and
- m and o are each independently 0, 1 or 2;
- or a pharmaceutically acceptable salt thereof.
A compound selected from the group consisting of
- 3-[4-(3-fluoro-benzyloxy)-phenoxy]-propionamide
- carbamic acid 2-[4-(3-fluoro-benzyloxy)-phenyl]-ethyl ester
- methyl-carbamic acid 4-(3-fluoro-benzloxy)-benzyl ester
- 2-[4-(4-chloro-benzyloxy)-phenoxy]-N-methyl-acetamide,
- 2-[4-(2-fluoro-benzyloxy)-phenoxy]-N-methyl-acetamide,
- 2-[4-(3-fluoro-benzyloxy)-phenoxy]-N-methyl-acetamide,
- 2-[4-(4-fluoro-benzyloxy)-phenoxy]-N-methyl-acetamide,
- (RS)-2-[4-(3-fluoro-benzyloxy)-phenoxy]-N-methyl-propionamide
- (RS)-2-[4-(3-chloro-benzyloxy)-phenoxy]-N-methyl-propionamide
- (S or R)-2-[4-(3-chloro-benzyloxy)-phenoxy]-N-methyl-propionamide,
- (RS)-2-[4-(3-fluoro-benzyloxy)-phenoxy]-N-methyl-propionamide,
- (RS)-2-[4-(3-chloro-benzyloxy)-phenoxy]-N-methyl-butyramide.
A pharmaceutical composition comprising a compound of the formula
- wherein
- R1 and R2 are each independently hydrogen or C1-C6-alkyl;
- R3 and R4 are each independently hydrogen or C1-C6-alkyl;
- R5 is CN, (C1-C6)-alkyl or (C1-C6)-alkoxy;
- and
- n is 1 or 2;
- and
- m and o are each independently 0, 1 or 2;
- or a pharmaceutically acceptable salt thereof
- and a pharmaceutically acceptable carrier.
A process for preparation of compounds of formula I
- wherein
- R1 and R2 are each independently hydrogen or C1-C6-alkyl;
- R3 and R4 are each independently hydrogen or C1-C6-alkyl;
- R5 is CN, (C1-C6) alkoxy;
- and
- n is 1 or 2;
- m and o is 0, 1 or 2;
- or a pharmaceutically acceptable salt thereof, which process comprises one of the following process
- a) reacting a compound of formula
- with a compound of formula
- wherein Y is a leaving group, to obtain a compound of formula
- b) reacting a compound of formula
- wherein R6 is C1-C6-alkyl, with an amine of formula
- to obtain a compound of formula
- c) reacting a compound of formula
- with KOCN or with
- R3—N═C═O VII
- to obtain a compound of formula
- d) reacting a compound of formula
- with a compound of formula HNR3R4 V
- to obtain a compound of formula
A compound selected from the group consisting of
- 2-[4-(4-cyano-benzyloxy)-phenoxy]-N-methyl-acetamide,
- (RS)-2-[4-(4-cyano-benzyloxy)-phenoxy]-N-methyl-propionamide, and
- (RS)-2-[4-(4-cyano-benzyloxy)-phenoxy]-N-methyl-butyramide.
A pharmaceutical composition comprising a compound selected from the group consisting of
- 2-[4-(4-chloro-benzyloxy)-phenoxy]-N-methyl-acetamide,
- 2-[4-(2-fluoro-benzyloxy)-phenoxy]-N-methyl-acetamide,
- 2-[4-(3-fluoro-benzyloxy)-phenoxy]-N-methyl-acetamide,
- 2-[4-(4-fluoro-benzyloxy)-phenoxy]-N-methyl-acetamide,
- (RS)-2-[4-(3-fluoro-benzyloxy)-phenoxy]-N-methyl-propionamide
- (RS)-2-[4-(3-chloro-benzyloxy)-phenoxy]-N-methyl-propionamide
- (S or R)-2-[4-(3-chloro-benzyloxy)-phenoxy]-N-methyl-propionamide,
- (RS)-2-[4-(3-fluoro-benzyloxy)-phenoxy]-N-methyl-butyramide, and
- (RS)-2-[4-(3-chloro-benzyloxy)-phenoxy]-N-methyl-butyramide.
A pharmaceutical composition comprising a compound selected from the group consisting of
- 2-[4-(4-cyano-benzyloxy)-phenoxy]-N-methyl-acetamide,
- (RS)-2-[4-(4-cyano-benzyloxy)-phenoxy]-N-methyl-propionamide, and
- (RS)-2-[4-(4-cyano-benzyloxy)-phenoxy]-N-methyl-butyramide.
Dependencies are inferred from the claim text.