Back to results
US 7,732,457 B2Granted
Amino-pyridines as inhibitors of β-secretase
AssigneeWyeth
InventorsMichael Sotirios Malamas, William Floyd Fobare, William Ronald Solvibile, Jr., Frank Eldridge Lovering, Jeffrey Scott Condon, Albert Jean Robichaud
Life of this patent
Estimating the term…
Abstract
The present invention provides an amino-pyridine compound of formula I The present invention also provides methods for the use thereof to inhibit β-secretase (BACE) and treat β-amyloid deposits and neurofibrillary tangles.
Claims9
A compound of formula Ia
- or a pharmaceutically acceptable salt thereof
- wherein
- Y is CH;
- R3 and R4 are each independently H, halogen, NR6R7, OR8, or an alkyl, haloalkyl or aryl group each group substituted with 0-4 substituents independently selected from the group consisting of halo, nitro, cyano, thiocyanato, cyanato, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, formyl, alkoxycarbonyl, carboxyl, alkanoyl, alkylthio, alkylsuphinyl, alkylsulphonyl, carbamoyl, alkylamido, phenyl, phenoxy, benzyl, benzyloxy and cycloalkyl;
- R5 is H or an alkyl group substituted with 0-4 substituents independently selected from the group consisting of halo, nitro, cyano, thiocyanato, cyanato, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, formyl, alkoxycarbonyl, carboxyl, alkanoyl, alkylthio, alkylsuphinyl, alkylsulphonyl, carbamoyl, alkylamido, phenyl, phenoxy, benzyl, benzyloxy and cycloalkyl;
- R6 and R7 are each independently H or an alkyl group substituted with 0-4 substituents independently selected from the group consisting of halo, nitro, cyano, thiocyanato, cyanato, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, formyl, alkoxycarbonyl, carboxyl, alkanoyl, alkylthio, alkylsuphinyl, alkylsulphonyl, carbamoyl, alkylamido, phenyl, phenoxy, benzyl, benzyloxy and cycloalkyl;
- R8 is H or alkyl or alkenyl each substituted with 0-4 substituents independently selected from the group consisting of halo, nitro, cyano, thiocyanato, cyanato, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, formyl, alkoxycarbonyl, carboxyl, alkanoyl, alkylthio, alkylsuphinyl, alkylsulphonyl, carbamoyl, alkylamido, phenyl, phenoxy, benzyl, benzyloxy and cycloalkyl;
- R9 is OR12;
- R10 and R11 are each independently H, halogen, OR13, or an alkyl or haloalkyl group each group substituted with 0-4 substituents independently selected from the group consisting of halo, nitro, cyano, thiocyanato, cyanato, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, formyl, alkoxycarbonyl, carboxyl, alkanoyl, alkylthio, alkylsuphinyl, alkylsulphonyl, carbamoyl, alkylamido, phenyl, phenoxy, benzyl, benzyloxy and cycloalkyl;
- R12 is pyrimidine group substituted with 0-4 substituents independently selected from the group consisting of halo, nitro, cyano, thiocyanato, cyanato, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, formyl, alkoxycarbonyl, carboxyl, alkanoyl, alkylthio, alkylsuphinyl, alkylsulphonyl, carbamoyl, alkylamido, phenyl, phenoxy, benzyl, benzyloxy and cycloalkyl;
- and
- R13 are each independently a H or an alkyl, aryl or group substituted with 0-4 substituents independently selected from the group consisting of halo, nitro, cyano, thiocyanato, cyanato, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, formyl, alkoxycarbonyl, carboxyl, alkanoyl, alkylthio, alkylsuphinyl, alkylsulphonyl, carbamoyl, alkylamido, phenyl, phenoxy, benzyl, benzyloxy and cycloalkyl.
9 more elements
A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and a compound of formula Ia
- or a pharmaceutically acceptable salt thereof
- wherein
- Y is CH;
- R3 and R4 are each independently H, halogen, NR6R7, OR8, or an alkyl, haloalkyl or aryl group each group substituted with 0-4 substituents independently selected from the group consisting of halo, nitro, cyano, thiocyanato, cyanato, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, formyl, alkoxycarbonyl, carboxyl, alkanoyl, alkylthio, alkylsuphinyl, alkylsulphonyl, carbamoyl, alkylamido, phenyl, phenoxy, benzyl, benzyloxy and cycloalkyl;
- R5 is H or an alkyl group substituted with 0-4 substituents independently selected from the group consisting of halo, nitro, cyano, thiocyanato, cyanato, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, formyl, alkoxycarbonyl, carboxyl, alkanoyl, alkylthio, alkylsuphinyl, alkylsulphonyl, carbamoyl, alkylamido, phenyl, phenoxy, benzyl, benzyloxy and cycloalkyl;
- R6 and R7 are each independently H or alkyl group substituted with 0-4 substituents independently selected from the group consisting of halo, nitro, cyano, thiocyanato, cyanato, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, formyl, alkoxycarbonyl, carboxyl, alkanoyl, alkylthio, alkylsuphinyl, alkylsulphonyl, carbamoyl, alkylamido, phenyl, phenoxy, benzyl, benzyloxy and cycloalkyl;
- R8 is H or alkyl or alkenyl each substituted with 0-4 substituents independently selected from the group consisting of halo, nitro, cyano, thiocyanato, cyanato, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, formyl, alkoxycarbonyl, carboxyl, alkanoyl, alkylthio, alkylsuphinyl, alkylsulphonyl, carbamoyl, alkylamido, phenyl, phenoxy, benzyl, benzyloxy and cycloalkyl;
- R9 is OR12,
- R10 and R11 are each independently H, halogen, OR13, or an alkyl or haloalkyl group each group substituted with 0-4 substituents independently selected from the group consisting of halo, nitro, cyano, thiocyanato, cyanato, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, formyl, alkoxycarbonyl, carboxyl, alkanoyl, alkylthio, alkylsuphinyl, alkylsulphonyl, carbamoyl, alkylamido, phenyl, phenoxy, benzyl, benzyloxy and cycloalkyl;
- R12 is pyrimidine group substituted with 0-4 substituents independently selected from the group consisting of halo, nitro, cyano, thiocyanato, cyanato, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, formyl, alkoxycarbonyl, carboxyl, alkanoyl, alkylthio, alkylsuphinyl, alkylsulphonyl, carbamoyl, alkylamido, phenyl, phenoxy, benzyl, benzyloxy and cycloalkyl;
- and
- R13 are each independently a H or an alkyl, aryl or group substituted with 0-4 substituents independently selected from the group consisting of halo, nitro, cyano, thiocyanato, cyanato, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, formyl, alkoxycarbonyl, carboxyl, alkanoyl, alkylthio, alkylsuphinyl, alkylsulphonyl, carbamoyl, alkylamido, phenyl, phenoxy, benzyl, benzyloxy and cycloalkyl.
9 more elements
Dependencies are inferred from the claim text.