US2014179925A1PendingUtilityA1

Methods for treating cognitive disorders using 3-aryl-3-hydroxy-2-amino-propionic acid amides, 3-heteroaryl-3-hydroxy-2-amino-propionic acid amides and related compounds

Assignee: ALLERGAN INCPriority: Sep 4, 2009Filed: Dec 18, 2013Published: Jun 26, 2014
Est. expirySep 4, 2029(~3.1 yrs left)· nominal 20-yr term from priority
C07D 405/06C07D 401/06C07D 215/14C07D 307/52C07D 213/50C07D 295/192C07D 409/06C07D 333/22
57
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Claims

Abstract

Disclosed herein are methods of treating a patient suffering from a cognitive disorder using compounds of Formulas 1 and 2 wherein the variables have the meaning disclosed in the specification

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . The use of a compound in the manufacture of a medicament for treating a cognitive disorder, wherein the compound has the following structure: 
       
         
           
           
               
               
           
         
         where R 1  is H or alkyl of 1 to 6 carbons, 
         R 2  is H, alkyl of 1 to 6 carbons or the R 1  and R 2  groups together with the nitrogen form a saturated or unsaturated 4, 5, 6 or 7 membered ring that optionally includes one or two heteroatoms independently selected from N, O and S, said 4, 5, 6 or 7 membered ring optionally being substituted with one or two COOH, CH 2 OH, OH, B(OH) 2 , halogen groups, cyano groups, or with one or two alkyl groups having 1 to 6 carbons, or one or two carbons of said rings being attached to an oxygen to form keto groups and said 4, 5, 6 or 7 membered ring optionally being condensed with an aromatic or non-aromatic 5 or 6 membered ring that optionally includes 1 or heteroatoms selected from N, O and S; 
         R 3  is independently selected from H, alkyl of 1 to 20 carbons, cycloalkyl of 3 to 6 carbons, aryl or heteroaryl, aryl-alkyl where the alkyl moiety has 1 to 4 carbons, aryl-(hydroxy)alkyl where the alkyl moiety has 1 to 4 carbons, heteroaryl-alkyl where the alkyl moiety has 1 to 4 carbons, or hetero-(hydroxy)alkyl where the alkyl moiety has 1 to 4 carbons, said aryl or heteroaryl groups being optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons and thioxy of 1 to 3 carbons, or R 3  is CO—R 7 , SO 2 R 7  or CO—O—R 7  where R 7  is H, alkyl of 1 to 1 to 20 carbons, alkyl of 1 to 20 carbons substituted with and NH 2  group or with an NH—COalkyl group where the alkyl group has one to 6 carbons, aryl or heteroaryl, aryl-alkyl where the alkyl moiety has 1 to 4 carbons or heteroaryl-alkyl where the alkyl moiety has 1 to 4 carbons, said aryl or heteroaryl groups being optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons and thioxy of 1 to 3 carbons; 
         R 4  is H, alkyl of 1 to 6 carbons or CO—R 8  where R 8  is alkyl of 1 to 6 carbons; 
         the wavy lines represent bonds connected to carbons having R or S configuration; 
         the dashed lines represent a bond or absence of a bond with the proviso that the ring containing the dashed lines is aromatic; 
         m, n and q are integers independently selected from 0, 1, 2 or 3 with the proviso that the sum of m, n and q is 2 or 3; 
         s is zero (0) or when X is N then s is zero (0) or 1; 
         W, X and Y independently represent a CH, CR 5 , CR 6  or a heteroatom selected independently of N, O and S, and 
         R 5  and R 6  are independently selected from H, halogen, alkyl of 1 to 6 carbons, halogen substituted alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons and thioxy of 1 to 3 carbons, phenyl, or 
         R 5  and R 6  together with the atoms to which they are attached jointly form a carbocyclic or a heterocyclic ring, the carbocyclic ring having 5 or 6 atoms in the ring, the heterocyclic ring having 5 or 6 atoms in the ring and 1 to 3 heteroatoms independently selected from N, O and S; 
         said carbocyclic or heterocyclic ring jointly formed by R 5  and R 6  being optionally substituted with 1 to 6 R 9  groups where R 9  is independently selected from halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons and thioxy of 1 to 3 carbons or a pharmaceutically acceptable salt of said compound with the proviso that Formula 1 does not cover compounds where R 4  is H, R 1  and R 2  jointly with the nitrogen form a pyrrolidino or morpholino ring, the sum of m, n and q is 3, and where none of W, X and Y represent a heteroatom with the further proviso that the formula does not cover the compounds of the formula below 
       
       
         
           
           
               
               
           
         
       
     
     
         2 . The use of  claim 1 , wherein the sum of the integers m, n and q is 3. 
     
     
         3 . The use of  claim 2 , wherein one of the W, X and Y groups is N. 
     
     
         4 . The use of  claim 3 , wherein R 5  and R 6  together with the atoms to which they are attached jointly form a carbocyclic or a heterocyclic ring. 
     
     
         5 . The use of  claim 2 , wherein none of the W, X and Y groups is a heteroatom. 
     
     
         6 . The use of  claim 5  wherein R 5  and R 6  together with the atoms to which they are attached jointly form a carbocyclic or a heterocyclic ring. 
     
     
         7 . The use of  claim 1 , wherein the sum of the integers m, n and q is 2 and at least one of W, X and Y is a heteroatom. 
     
     
         8 . The use of  claim 7 , wherein only one of W, X and Y represents a heteroatom. 
     
     
         9 . The use of  claim 7 , wherein two of the W, X and Y groups each represent an independently selected heteroatom. 
     
     
         10 . The use of  claim 1 , wherein R 4  is H. 
     
     
         11 . The use of  claim 10 , wherein both R 3  groups are H. 
     
     
         12 . The use of  claim 10 , wherein one R 3  group is H and the other R 3  group is CO—R 7  or alkyl of 1 to 20 carbons. 
     
     
         13 . The use of  claim 10 , wherein R 3  is independently selected from H and alkyl of 1 to 10 carbons. 
     
     
         14 . The use of  claim 1 , wherein R 4  is CO—R 8 . 
     
     
         15 . The use of  claim 1 , wherein R 1  and R 2  together with the nitrogen form a 4, 5, 6 or 7 membered ring. 
     
     
         16 . The use of  claim 15 , wherein R 1  and R 2  together with the nitrogen form a 5 membered ring. 
     
     
         17 . The use of  claim 15 , wherein R 1  and R 2  together with the nitrogen form a 6 membered ring. 
     
     
         18 . The use of  claim 1 , wherein both R 5  and R 6  are hydrogen. 
     
     
         19 . The use of a compound in the manufacture of a medicament for treating a cognitive disorder, wherein the compound has the following structure: 
       
         
           
           
               
               
           
         
         where R 1  is H or alkyl of 1 to 6 carbons, 
         R 2  is H, alkyl of 1 to 6 carbons or the R 1  and R 2  groups together with the nitrogen form a saturated or unsaturated 4, 5, 6 or 7 membered ring that optionally includes one or two heteroatoms independently selected from N, O and S, said 4, 5, 6 or 7 membered ring optionally being substituted with one or two COOH, CH 2 OH, OH, B(OH) 2 , halogen groups, cyano groups or with one or two alkyl groups having 1 to 6 carbons; 
         R 3  is H, CO—R 7  or CO—O—R 7  where R 7  is H, alkyl of 1 to 1 to 20 carbons, cycloalkyl of 3 to 6 carbons, aryl or heteroaryl, aryl-alkyl, aryl(hydroxy)alkyl, heteroaryl-alkyl or heteroalkyl(hydroxy)alkyl where the alkyl moiety has 1 to 4 carbons, said aryl or heteroaryl groups being optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons and thioxy of 1 to 3 carbons; 
         R 4  is H, alkyl of 1 to 6 carbons, or CO—R 8  where R 8  is alkyl of 1 to 6 carbons, 
         R 5  and R 6  are independently selected from H, halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons and thioxy of 1 to 3 carbons, or 
         R 5  and R 6  together with the atoms to which they are attached jointly form a carbocyclic or a heterocyclic ring, the carbocyclic ring having 5 or 6 atoms in the ring, the heterocyclic ring having 5 or 6 atoms in the ring and 1 to 3 heteroatoms independently selected from N, O and S; 
         said carbocyclic or heterocyclic ring jointly formed by R 5  and R 6  being optionally substituted with 1 to 6 R 9  groups where R 9  is independently selected from halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons, and 
         the wavy lines represent bonds of the alpha or beta configuration, or any pharmaceutically acceptable salt of said compound. 
       
     
     
         20 . The use of  claim 19 , wherein R 4  is H. 
     
     
         21 . The use of  claim 19 , wherein both R 3  groups are H. 
     
     
         22 . The use of  claim 19 , wherein both R 5  and R 6  are hydrogen. 
     
     
         23 . The use of  claim 19 , wherein the compound has the formula 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt of said compound. 
       
     
     
         24 . The use of  claim 23 , wherein R 4  is H. 
     
     
         25 . The use of  claim 23 , wherein both R 3  groups are H. 
     
     
         26 . The use of a compound in the manufacture of a medicament for treating a cognitive disorder, wherein the compound has the following structure: 
       
         
           
           
               
               
           
         
         where R 1  is H or alkyl of 1 to 6 carbons, 
         R 2  is alkyl of 1 to 6 carbons or the R 1  and R 2  groups together with the nitrogen form a saturated or unsaturated 4, 5, 6 or 7 membered ring that optionally includes one or two heteroatoms independently selected from N, O and S, said 4, 5, 6 or 7 membered ring optionally being substituted with one or two COOH, CH 2 OH, OH, B(OH) 2 , halogen groups, cyano groups, or with one or two alkyl groups having 1 to 6 carbons, 
         R 3  is H, CO—R 7  or CO—O—R 7  where R 7  is H, alkyl of 1 to 1 to 20 carbons, aryl or heteroaryl, cycloalkyl of 3 to 6 carbons, aryl-alkyl aryl(hydroxy)alkyl, heteroaryl-alkyl or heteroaryl(hydroxy)alkyl where the alkyl moiety has 1 to 4 carbons, said aryl or heteroaryl groups being optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons and thioxy of 1 to 3 carbons; 
         R 4  is H, alkyl of 1 to 6 carbons, or CO—R 8  where R 8  is alkyl of 1 to 6 carbons; 
         R 5  and R 6  are independently selected from H, halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons, thioxy of 1 to 3 carbons and phenyl, or 
         R 5  and R 6  together with the atoms to which they are attached jointly form a carbocyclic or a heterocyclic ring, the carbocyclic ring having 5 or 6 atoms in the ring, the heterocyclic ring having 5 or 6 atoms in the ring and 1 to 3 heteroatoms independently selected from N, O and S; 
         said carbocyclic or heterocyclic ring jointly formed by R 5  and R 6  being optionally substituted with 1 to 6 R 9  groups where R 9  is independently selected from halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons and thioxy of 1 to 3 carbons, and the wavy lines represent bonds connected to carbons having R or S of configuration, with the proviso that the claim does not cover compounds where R 4  is H, R 1  and R 2  jointly with the nitrogen form a pyrrolidino or morpholino ring, or any pharmaceutically acceptable salt of said compound. 
       
     
     
         27 . The use of a compound in the manufacture of a medicament for treating a cognitive disorder, wherein the compound has the following structure: 
       
         
           
           
               
               
           
         
         where X is O or S; 
         R 1  is H or alkyl of 1 to 6 carbons, 
         R 2  is H, alkyl of 1 to 6 carbons or the R 1  and R 2  groups together with the nitrogen form a saturated or unsaturated 5 or 6 membered ring that optionally includes one or two heteroatoms independently selected from N, O and S, said 4, 5, 6 or 7 membered ring optionally being substituted with one or two COOH, CH 2 OH, OH, B(OH) 2 , halogen groups or cyano groups with one or two alkyl groups having 1 to 6 carbons, 
         R 3  is H, CO—R 7  or CO—O—R 7  where R 7  is H, alkyl of 1 to 1 to 20 carbons, aryl or heteroaryl, aryl-alkyl, aryl(hydroxy)alkyl, heteroaryl-alkyl or heteroaryl(hydroxy)alkyl where the alkyl moiety has 1 to 4 carbons, said aryl or heteroaryl groups being optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons and thioxy of 1 to 3 carbons; 
         R 4  is H, alkyl of 1 to 6 carbons, or CO—R 8  where R 8  is alkyl of 1 to 6 carbons; 
         R 5  and R 6  are independently selected from H, halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons and thioxy of 1 to 3 carbons, or 
         R 5  and R 6  together with the atoms to which they are attached jointly form a carbocyclic or a heterocyclic ring, the carbocyclic ring having 5 or 6 atoms in the ring, the heterocyclic ring having 5 or 6 atoms in the ring and 1 to 3 heteroatoms independently selected from N, O and S; 
         said carbocyclic or heterocyclic ring jointly formed by R 5  and R 6  being optionally substituted with 1 to 6 R 9  groups where R 9  is independently selected from halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons, and 
         the wavy lines represent bonds connected to carbons having R or S configuration, or any pharmaceutically acceptable salt of said compound 
         with the further proviso that the claim does not cover the compound shown below 
       
       
         
           
           
               
               
           
         
       
     
     
         28 . The use of a compound in the manufacture of a medicament for treating a cognitive disorder, wherein the compound has the following structure: 
       
         
           
           
               
               
           
         
         where R 1  is H or alkyl of 1 to 6 carbons, 
         R 2  is H, alkyl of 1 to 6 carbons or the R 1  and R 2  groups together with the nitrogen form a saturated or unsaturated 4, 5, 6 or 7 membered ring that optionally includes one or two heteroatoms independently selected from N, O and S, said 4, 5, 6 or 7 membered ring optionally being substituted with one or two COOH, CH 2 OH, OH, B(OH) 2 , halogen or cyano groups or with one or two alkyl groups having 1 to 6 carbons, or one or two carbons of said rings being attached to an oxygen to form keto groups and said 4, 5, 6 or 7 membered ring optionally being condensed with an aromatic or non-aromatic 5 or 6 membered ring that optionally includes 1 or heteroatoms selected from N, O and S; 
         R 3  is independently selected from H, alkyl of 1 to 20 carbons, cycloalkyl of 3 to 6 carbons, aryl or heteroaryl, aryl-alkyl where the alkyl moiety has 1 to 4 carbons, aryl-(hydroxy)alkyl where the alkyl moiety has 1 to 4 carbons, heteroaryl-alkyl where the alkyl moiety has 1 to 4 carbons or hetero-(hydroxy)alkyl where the alkyl moiety has 1 to 4 carbons, said aryl or heteroaryl groups being optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons and thioxy of 1 to 3 carbons, or R 3  is CO—R 7 , SO 2 R 7  or CO—O—R 7  where R 7  is H, alkyl of 1 to 1 to 20 carbons, alkyl of 1 to 20 carbons substituted with and NH 2  group or with an NH—COalkyl group where the alkyl group has one to 6 carbons aryl or heteroaryl, aryl-alkyl where the alkyl moiety has 1 to 4 carbons or heteroaryl-alkyl where the alkyl moiety has 1 to 4 carbons, said aryl or heteroaryl groups being optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons and thioxy of 1 to 3 carbons; 
         the wavy lines represent bonds connected to carbons having R or S configuration; 
         the dashed lines represent a bond or absence of a bond with the proviso that the ring containing the dashed lines is aromatic; 
         R 9  and R 10  are one of the combinations selected from the group consisting of (1) R 9  is NOR 11  and R 10  does not exist, (2) R 9  is OR 11  and R 10  is alkyl of 1 to 6 carbons, (3) when the dashed lines between carbons 2 and 3 of the propionic acid moiety represent a bond then R 9  is H or alkyl of 1 to 6 carbons and R 10  does not exist; 
         R 11  is H, alkyl of 1 to 6 carbons or CO—R 12  where R 12  is alkyl of 1 to 6 carbons; 
         m, n and q are integers independently selected from 0, 1, 2 or 3 with the proviso that the sum of m, n and q is 2 or 3; 
         is zero (0) or when X is N then s is zero (0) or 1; 
         W, X and Y independently represent a CH, CR 5 , CR 6  or a heteroatom selected independently of N, O and S, and 
         R 5  and R 6  are independently selected from H, halogen, alkyl of 1 to 6 carbons, halogen substituted alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons and thioxy of 1 to 3 carbons, phenyl, or 
         R 5  and R 6  together with the atoms to which they are attached jointly form a carbocyclic or a heterocyclic ring, the carbocyclic ring having 5 or 6 atoms in the ring, the heterocyclic ring having 5 or 6 atoms in the ring and 1 to 3 heteroatoms independently selected from N, O and S; 
         said carbocyclic or heterocyclic ring jointly formed by R 5  and R 6  being optionally substituted with 1 to 6 R 12  groups where R 12  is independently selected from halogen, alkyl of 1 to 6 carbons, alkoxy of 1 to 6 carbons and thioxy of 1 to 3 carbons or a pharmaceutically acceptable salt of said compound. 
       
     
     
         29 . The use of  claim 28 , wherein the sum of the integers m, n and q is 3. 
     
     
         30 . The use of  claim 28 , wherein one of the W, X and Y groups is N. 
     
     
         31 . The use of  claim 28 , wherein the R 1  and R 2  groups together with the nitrogen form a 5-membered ring. 
     
     
         32 . The use of  claim 28 , wherein R 9  is NOR 11  and R 10  does not exist. 
     
     
         33 . The use of  claim 28 , wherein R 9  is methyl and R 10  is OR 11 . 
     
     
         34 . The use of  claim 28 , wherein the dashed line between carbons 2 and 3 represents a bond. 
     
     
         35 . The use of a compound in the manufacture of a medicament for treating a cognitive disorder, wherein the compound has the following structure: 
       
         
           
           
               
               
           
         
       
     
     
         36 . The use of  claim 35 , wherein the compound is (2S,3S)-2-amino-3-hydroxy-1-(pyrrolidin-1-yl)-3-(thiophen-3-yl)propan-1-one. 
     
     
         37 . The use of  claim 35 , wherein the compound is (2S,3R)-2-amino-3-hydroxy-1-(pyrrolidin-1-yl)-3-(thiophen-3-yl)propan-1-one. 
     
     
         38 . The use of  claim 35 , wherein the compound is (2R,3S)-2-amino-3-hydroxy-1-(pyrrolidin-1-yl)-3-(thiophen-3-yl)propan-1-one. 
     
     
         39 . The use of  claim 35 , wherein the compound is (2R,3R)-2-amino-3-hydroxy-1-(pyrrolidin-1-yl)-3-(thiophen-3-yl)propan-1-one. 
     
     
         40 . The use of a compound in the manufacture of a medicament for treating a cognitive disorder, wherein the compound has the following structure: 
       
         
           
           
               
               
           
         
       
     
     
         41 . The use of  claim 40 , wherein the compound is (2S,3S)-2-amino-3-hydroxy-3-(pyridin-3-yl)-1-(pyrrolidin-1-yl)propan-1-one. 
     
     
         42 . The use of  claim 40 , wherein the compound is (2S,3R)-2-amino-3-hydroxy-3-(pyridin-3-yl)-1-(pyrrolidin-1-yl)propan-1-one. 
     
     
         43 . The use of  claim 40 , wherein the compound is (2R,3S)-2-amino-3-hydroxy-3-(pyridin-3-yl)-1-(pyrrolidin-1-yl)propan-1-one. 
     
     
         44 . The use of  claim 40 , wherein the compound is (2R,3R)-2-amino-3-hydroxy-3-(pyridin-3-yl)-1-(pyrrolidin-1-yl)propan-1-one. 
     
     
         45 . The use of a compound in the manufacture of a medicament for treating a cognitive disorder, wherein the compound has the following structure: 
       
         
           
           
               
               
           
         
       
     
     
         46 . The use of  claim 45 , wherein the compound is (2S,3S)-2-amino-3-hydroxy-3-(pyridin-4-yl)-1-(pyrrolidin-1-yl)propan-1-one. 
     
     
         47 . The use of  claim 45 , wherein the compound is (2S,3R)-2-amino-3-hydroxy-3-(pyridin-4-yl)-1-(pyrrolidin-1-yl)propan-1-one. 
     
     
         48 . The use of  claim 45 , wherein the compound is (2R,3S)-2-amino-3-hydroxy-3-(pyridin-4-yl)-1-(pyrrolidin-1-yl)propan-1-one. 
     
     
         49 . The use of  claim 45 , wherein the compound is (2R,3R)-2-amino-3-hydroxy-3-(pyridin-4-yl)-1-(pyrrolidin-1-yl)propan-1-one. 
     
     
         50 . The use of a compound in the manufacture of a medicament for treating a cognitive disorder, wherein the compound has the following structure: 
       
         
           
           
               
               
           
         
       
     
     
         51 . The use of  claim 50 , wherein the compound is (2S,3S)-2-amino-3-hydroxy-1-(piperidin-1-yl)-3-(pyridin-4-yl)propan-1-one. 
     
     
         52 . The use of  claim 50 , wherein the compound is (2S,3R)-2-amino-3-hydroxy-1-(piperidin-1-yl)-3-(pyridin-4-yl)propan-1-one. 
     
     
         53 . The use of  claim 50 , wherein the compound is (2R,3S)-2-amino-3-hydroxy-1-(piperidin-1-yl)-3-(pyridin-4-yl)propan-1-one. 
     
     
         54 . The use of  claim 50 , wherein the compound is (2R,3R)-2-amino-3-hydroxy-1-(piperidin-1-yl)-3-(pyridin-4-yl)propan-1-one. 
     
     
         55 . The use of a compound in the manufacture of a medicament for treating a cognitive disorder, wherein the compound has the following structure 
       
         
           
           
               
               
           
         
       
     
     
         56 . The use of  claim 55 , wherein the compound is (2S,3S)-2-amino-3-(furan-3-yl)-3-hydroxy-1-(pyrrolidin-1-yl)propan-1-one. 
     
     
         57 . The use of  claim 55 , wherein the compound is (2S,3R)-2-amino-3-(furan-3-yl)-3-hydroxy-1-(pyrrolidin-1-yl)propan-1-one. 
     
     
         58 . The use of  claim 55 , wherein the compound is (2R,3S)-2-amino-3-(furan-3-yl)-3-hydroxy-1-(pyrrolidin-1-yl)propan-1-one. 
     
     
         59 . The use of  claim 55 , wherein the compound is (2R,3R)-2-amino-3-(furan-3-yl)-3-hydroxy-1-(pyrrolidin-1-yl)propan-1-one. 
     
     
         60 . The use of a compound in the manufacture of a medicament for treating a cognitive disorder, wherein the compound has the following structure 
       
         
           
           
               
               
           
         
       
     
     
         61 . The use of  claim 60 , wherein the compound is (2S,3S)-2-amino-3-hydroxy-1-(pyrrolidin-1-yl)-3-(quinolin-4-yl)propan-1-one. 
     
     
         62 . The use of  claim 60 , wherein the compound is (2S,3R)-2-amino-3-hydroxy-1-(pyrrolidin-1-yl)-3-(quinolin-4-yl)propan-1-one. 
     
     
         63 . The use of  claim 60 , wherein the compound is (2R,3S)-2-amino-3-hydroxy-1-(pyrrolidin-1-yl)-3-(quinolin-4-yl)propan-1-one. 
     
     
         64 . The use of  claim 60 , wherein the compound is (2R,3R)-2-amino-3-hydroxy-1-(pyrrolidin-1-yl)-3-(quinolin-4-yl)propan-1-one. 
     
     
         65 . The use of a compound in the manufacture of a medicament for treating a cognitive disorder, wherein the compound has the following structure: 
       
         
           
           
               
               
           
         
       
     
     
         66 . The use of  claim 65 , wherein the compound is (2S,3S)-2-amino-3-hydroxy-1-(pyrrolidin-1-yl)-3-p-tolylpropan-1-one. 
     
     
         67 . The use of  claim 65 , wherein the compound is (2S,3R)-2-amino-3-hydroxy-1-(pyrrolidin-1-yl)-3-p-tolylpropan-1-one. 
     
     
         68 . The use of  claim 65 , wherein the compound is (2R,3S)-2-amino-3-hydroxy-1-(pyrrolidin-1-yl)-3-p-tolylpropan-1-one. 
     
     
         69 . The use of  claim 65 , wherein the compound is (2R,3R)-2-amino-3-hydroxy-1-(pyrrolidin-1-yl)-3-p-tolylpropan-1-one. 
     
     
         70 . The use of a compound in the manufacture of a medicament for treating a cognitive disorder, wherein the compound has the following structure: 
       
         
           
           
               
               
           
         
       
     
     
         71 . The use of  claim 70 , wherein the compound is (2S,3S)-2-amino-3-(biphenyl-4-yl)-3-hydroxy-1-(pyrrolidin-1-yl)propan-1-one. 
     
     
         72 . The use of  claim 70 , wherein the compound is (2S,3R)-2-amino-3-(biphenyl-4-yl)-3-hydroxy-1-(pyrrolidin-1-yl)propan-1-one. 
     
     
         73 . The use of  claim 70 , wherein the compound is (2R,3S)-2-amino-3-(biphenyl-4-yl)-3-hydroxy-1-(pyrrolidin-1-yl)propan-1-one. 
     
     
         74 . The use of  claim 70 , wherein the compound is (2R,3R)-2-amino-3-(biphenyl-4-yl)-3-hydroxy-1-(pyrrolidin-1-yl)propan-1-one. 
     
     
         75 . The use according to any of the preceding claims, wherein the cognitive disorder is selected from the group consisting of an agnosia, an amnesia, an aphasia, an apraxia, a delirium, a dementia, and a learning disorder. 
     
     
         76 . The use according to  claim 75 , wherein the cognitive disorder is selected from the group consisting of AIDS dementia complex, Binswanger's disease, dementia with Lewy Bodies, frontotemporal dementia, mild cognitive impairment, multi-infarct dementia, Pick's disease, semantic dementia, senile dementia, and vascular dementia. 
     
     
         77 . The use according to  claim 75 , wherein the learning disorder is selected from the group consisting of Asperger's syndrome, attention deficit disorder,
 attention deficit hyperactivity disorder, autism, childhood disintegrative disorder, and Rett syndrome.   
     
     
         78 . The use according to  claim 75 , wherein the aphasia is progressive non-fluent aphasia. 
     
     
         79 . The use according to any of the preceding claims, wherein the cognitive disorder is associated with neurodegenerative disease, injury to the brain, psychiatric disorders, or chronic pain. 
     
     
         80 . The use according to  claim 79 , wherein the neurodegenerative disease is selected from the group consisting of Alzheimer's disease, corticobasal degeneration, Creutzfeldt-Jacob disease, frontotemporal lobar degeneration, Huntington disease, multiple sclerosis, normal pressure hydrocephalus, organic chronic brain syndrome, Parkinson's disease, Pick disease, progressive supranuclear palsy, and senile dementia (Alzheimer type). 
     
     
         81 . The use according to  claim 79 , wherein the injury to the brain is selected from the group consisting of chronic subdural hematoma, concussion, intracerebral hemorrhage, encephalitis, meningitis, septicemia, drug intoxication, and drug abuse. 
     
     
         82 . The use according to  claim 79 , wherein the psychiatric disorders are selected from the group consisting of anxiety disorders, dissociative disorders, mood disorders, schizophrenia, and somatoform and factitious disorders.

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