US2010210592A1PendingUtilityA1

Amines or amino alcohols as glyt1 inhibitors

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Assignee: KOLCZEWSKI SABINEPriority: Feb 18, 2009Filed: Feb 11, 2010Published: Aug 19, 2010
Est. expiryFeb 18, 2029(~2.6 yrs left)· nominal 20-yr term from priority
Inventors:Sabine KolczewskiHans-Peter MartyRobert NarquizianEmmanuel PinardHenri Stalder
A61P 43/00A61P 25/18A61P 25/28A61P 25/00C07C 215/68C07D 305/06C07C 317/32C07D 211/46C07D 213/61C07D 213/65C07C 2601/08C07D 333/20C07D 309/12C07D 277/28C07D 213/71C07C 2601/02C07D 213/73C07D 309/06A61K 31/16C07D 213/64C07C 2601/14C07D 307/12C07C 217/70C07D 335/02C07C 233/43C07D 213/38C07C 237/30C07C 215/30C07D 405/12C07D 239/26C07D 307/20C07D 215/30
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Claims

Abstract

The invention relates to the use of compounds of formula I wherein the substituents are described in the description and claims for the treatment of psychoses, dysfunction in memory and learning, schizophrenia, dementia, attention deficit disorders or Alzheimer's disease. The invention also relates to some compounds of formula I and pharmaceutical compositions containing them.

Claims

exact text as granted — not AI-modified
1 . A method for the treatment of a disorder selected from the group consisting of psychoses, dysfunction in memory and learning, schizophrenia, dementia, attention deficit disorder, and Alzheimer's disease which comprises administering a compound of formula I 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is hydrogen, halogen, lower alkyl, or lower alkoxy, 
         R 2  is hydrogen, halogen, lower alkyl, or lower alkoxy, 
         R 3  is hydrogen, halogen, lower alkoxy or lower alkyl, wherein the lower alkyl is optionally substituted by halogen, 
         R 4  is a) hydrogen,
 b) halogen, 
 c) lower alkyl, optionally substituted by halogen, lower alkoxy or hydroxyl, 
 d) lower alkoxy, optionally substituted by halogen, hydroxyl, cycloalkyl or heterocyclyl, 
 e) —NR 11 R 12 , 
 f) —S(O) 2 -lower alkyl, 
 g) —Si(lower alkyl) 3 , 
 h) —O-cycloalkyl, 
 i) —O-aryl, 
 j) —O-heteroaryl, 
 k) —O-heterocyclyl, 
 l) aryl, 
 m) heteroaryl, or 
 n) heterocyclyl, 
 wherein each of the cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, —NR 11 R 12 , lower alkoxy, halogen-lower alkoxy, or —S(O) 2 -lower alkyl, 
 and wherein each S being part of a heterocyclyl is optionally substituted by oxo, 
 
         R 5  is halogen, lower alkyl, or lower alkoxy, 
         R 6  is hydrogen or lower alkyl, 
         R 7  is hydrogen or lower alkyl, 
         R 8  is hydrogen or lower alkyl, 
         R 9  is hydrogen, halogen, lower alkyl, or lower alkoxy, 
         R 10  is hydrogen, halogen, lower alkyl, lower alkoxy or phenyl, wherein the phenyl is optionally substituted by halogen, lower alkyl, or —S(O) 2 -lower alkyl, 
         R 11  is hydrogen or lower alkyl, 
         R 12  is hydrogen or lower alkyl, 
         X is a) N and Y is C—R 10 ,
 b) C—R 9  and Y is N, or 
 c) C—R 9  and Y is C—R 10 , and 
 
         n is 0 or 1, 
         with the proviso that R 8  is lower alkyl, when 
         a) R 1  is hydrogen, R 2  is hydrogen, R 3  is halogen, R 4  is halogen, R 6  is hydrogen, R 7  is hydrogen, R 9  is hydrogen, R 10  is halogen, n is 0, X is C—R 9  and Y is C—R 10 ; 
         b) R 1  is hydrogen, R 2  is hydrogen, R 3  is lower alkoxy, R 4  is lower alkoxy, R 6  is hydrogen, R 7  is hydrogen, R 9  is hydrogen, R 10  is halogen, n is 0, X is C—R 9  and Y is C—R 10 ; 
         c) R 1  is hydrogen, R 2  is hydrogen, R 3  is halogen, R 4  is heterocyclyl, R 6  is hydrogen, R 7  is hydrogen, R 9  is hydrogen, R 10  is hydrogen, n is 0, X is C—R 9  and Y is C—R 10 ; 
         d) R 1  is hydrogen, R 2  is hydrogen, R 3  is halogen, R 4  is hydrogen, R 6  is hydrogen, R 7  is hydrogen, R 9  is halogen, R 10  is hydrogen, n is 0, X is C—R 9  and Y is C—R 10 ; 
         e) R 1  is hydrogen, R 2  is hydrogen, R 3  is halogen, R 4  is hydrogen, R 6  is lower alkyl, R 7  is hydrogen, R 9  is hydrogen, n is 0, X is C—R 9  and Y is N; or 
         f) R 1  is hydrogen, R 2  is hydrogen, R 3  is halogen, R 4  is hydrogen, R 6  is lower alkyl, R 7  is hydrogen, R 10  is hydrogen, n is 0, X is N and Y is C—R 10 ; 
         or a pharmaceutically active salt or ester thereof. 
       
     
     
         2 . A compound of formula I 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is hydrogen, halogen or lower alkyl, 
         R 2  is hydrogen, halogen or lower alkyl, 
         R 3  is halogen or lower alkyl, which lower alkyl is optionally substituted by halogen, 
         R 4  is a) lower alkyl, optionally substituted by halogen or lower alkoxy,
 b) lower alkoxy, optionally substituted by halogen, hydroxyl, cycloalkyl or heterocyclyl, 
 c) —Si(lower alkyl) 3 , 
 d) —O-cycloalkyl, optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, 
 e) —O-aryl, optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, 
 f) —O-heteroaryl, optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, 
 g) —O-heterocyclyl, optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, 
 wherein each S being part of a heterocyclyl is optionally substituted by oxo, 
 h) heteroaryl, optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, 
 i) aryl, substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, or 
 j) heterocyclyl, optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, 
 and R 4  is hydrogen when R 10  is phenyl, wherein the phenyl is optionally substituted by halogen, lower alkyl, or —S(O) 2 -lower alkyl, 
 and when R 6  is lower alkyl, R 4  is 
 a) lower alkyl, optionally substituted by halogen or lower alkoxy, 
 b) lower alkoxy, optionally substituted by halogen, hydroxyl, cycloalkyl or heterocyclyl, 
 c) —Si(lower alkyl) 3 , 
 d) —O-cycloalkyl, optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, 
 e) —O-aryl, optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, 
 f) —O-heteroaryl, optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, 
 g) —O-heterocyclyl, optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, 
 wherein each S being part of a heterocyclyl is optionally substituted by oxo, 
 h) heteroaryl, optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, 
 i) aryl, optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, 
 j) heterocyclyl, optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, 
 
         R 5  is halogen or lower alkyl, 
         R 6  is hydrogen or lower alkyl, 
         R 7  is hydrogen or lower alkyl, 
         R 8  is hydrogen or lower alkyl, 
         R 9  is hydrogen, halogen, lower alkyl or lower alkoxy, 
         R 10  is hydrogen, halogen, lower alkyl or lower alkoxy, 
         R 11  is hydrogen or lower alkyl, 
         R 12  is hydrogen or lower alkyl, 
         X is a) N and Y is C—R 10 ,
 b) C—R 9  and Y is N, or 
 c) C—R 9  and Y is C—R 10 , and 
 
         n is 0 or 1, 
         with the proviso that R 8  is lower alkyl, when 
         a) R 1  is hydrogen, R 2  is hydrogen, R 3  is methyl, R 4  is methyl, R 6  is hydrogen, R 7  is hydrogen, R 9  is hydrogen, R 10  is hydrogen, n is 0, X is C—R 9  and Y is C—R 10 ; 
         b) R 1  is hydrogen, R 2  is hydrogen, R 3  is methyl, R 4  is methyl, R 6  is hydrogen, R 7  is ethyl, R 9  is methyl, R 10  is hydrogen, n is 0, X is C—R 9  and Y is C—R 10 ; 
         c) R 1  is hydrogen, R 2  is hydrogen, R 3  is t-butyl, R 4  is t-butyl, R 6  is hydrogen, R 7  is hydrogen, R 9  is hydrogen, R 10  is hydrogen, n is 0, X is C—R 9  and Y is C—R 10 ; 
         d) R 1  is hydrogen, R 2  is hydrogen, R 3  is chloro, R 4  is hydrogen, R 6  is hydrogen, R 7  is hydrogen, R 9  is hydrogen, R 10  is hydrogen, n is 0, X is C—R 9  and Y is C—R 10 ; 
         e) R 1  is hydrogen, R 2  is hydrogen, R 3  is chloro, R 4  is morpholino, R 6  is hydrogen, R 7  is hydrogen, R 9  is hydrogen, R 10  is hydrogen, n is 0, X is C—R 9  and Y is C—R 10 ; 
         f) R 1  is hydrogen, R 2  is hydrogen, R 3  is chloro, R 4  is hydrogen, R 6  is hydrogen, R 7  is hydrogen, R 9  is chloro, R 10  is hydrogen, n is 0, X is C—R 9  and Y is C—R 10 ; 
         g) R 1  is hydrogen, R 2  is hydrogen, R 3  is chloro, R 4  is hydrogen, R 6  is methyl, R 7  is hydrogen, R 9  is hydrogen, n is 0, X is C—R 9  and Y is N; or 
         h) R 1  is hydrogen, R 2  is hydrogen, R 3  is chloro, R 4  is hydrogen, R 6  is methyl, R 7  is hydrogen, R 10  is hydrogen, n is 0, X is N and Y is C—R 10 ; 
         or a pharmaceutically active salt or ester thereof. 
       
     
     
         3 . The compound of  claim 2 , wherein R 1  is hydrogen. 
     
     
         4 . The compound of  claim 2 , wherein R 2  is hydrogen or halogen. 
     
     
         5 . The compound of  claim 4 , wherein R 2  is hydrogen, chloro or fluoro. 
     
     
         6 . The compound of  claim 2 , wherein R 3  is halogen or lower alkyl. 
     
     
         7 . The compound of  claim 6 , wherein R 3  is chloro or methyl. 
     
     
         8 . The compound of  claim 2 , wherein R 4  is
 a) lower alkoxy, optionally substituted by halogen, hydroxyl, cycloalkyl or heterocyclyl,   b) —O-aryl, or   c) —O-heterocyclyl, wherein each S being part of a heterocyclyl is optionally substituted by oxo.   
     
     
         9 . The compound of  claim 2 , wherein R 4  is —O-tetrahydropyranyl, —O-tetrahydrofuranyl, isopropoxy, tetrahydrofuranyl-ethoxy-, 4-chloro-2-hydroxy-butoxy-, 2-oxetanyl-propoxy-, 1,1,2,2-tetrafluoro-ethoxy-, chloro-hydroxy-isopentyloxy-, —O-tetrahydrothiopyranyl dioxide, tetrahydropyranyl-ethoxy-, 2,2,2-trifluoro-ethoxy-, 2-cyclopropyl-ethoxy-, —O-cyclopentyl, —O-cyclohexyl, i-butoxy, sec-butoxy, difluoro-isopropoxy-, —O-phenyl, 2,2,3,3,3-pentafluoro-propoxy- or trifluoro-isopropoxy-. 
     
     
         10 . The compound of  claim 2 , wherein R 5  is fluoro or methyl. 
     
     
         11 . The compound of  claim 2 , wherein R 6  is hydrogen. 
     
     
         12 . The compound of  claim 2 , wherein R 7  is hydrogen. 
     
     
         13 . The compound of  claim 2 , wherein R 8  is hydrogen. 
     
     
         14 . The compound of  claim 2 , wherein R 9  is hydrogen, halogen or lower alkyl. 
     
     
         15 . The compound of  claim 14 , wherein R 9  is hydrogen, fluoro or methyl. 
     
     
         16 . The compound of  claim 2 , wherein R 10  is hydrogen or halogen. 
     
     
         17 . The compound of  claim 16 , wherein R 10  is hydrogen or fluoro. 
     
     
         18 . The compound of  claim 2 , wherein n is 0. 
     
     
         19 . The compound of  claim 2 , wherein n is 1. 
     
     
         20 . The compound of  claim 2 , having formula Ia, 
       
         
           
           
               
               
           
         
         or a pharmaceutically active salt or ester thereof. 
       
     
     
         21 . The compound of  claim 2 , having formula Ib, 
       
         
           
           
               
               
           
         
         or a pharmaceutically active salt or ester thereof. 
       
     
     
         22 . The compound of  claim 2 , selected from the group consisting of
 rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-(3-fluoro-3′-methanesulfonyl-biphenyl-4-yl)-ethanol trifluoroacetate,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(5-fluoro-pyridin-3-yl)-2-methyl-phenyl]]-ethanol dihydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(5-fluoro-pyridin-3-yl)-3-methoxy-phenyl]-ethanol dihydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(5-fluoro-pyridin-3-yl)-2-methoxy-phenyl]-ethanol dihydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-(3′-methanesulfonyl-biphenyl-3-yl)-ethanol trifluoroacetate,   (1R,2S or 1S,2R)-2-Amino-2-(3,4-dichloro-phenyl)-1-(3-fluoro-3′-methanesulfonyl-biphenyl-4-yl)-ethanol hydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-(3′-methanesulfonyl-biphenyl-4-yl)-ethanol trifluoroacetate,   (1R,2S or 1S,2R)-2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(5-fluoro-pyridin-3-yl)-phenyl]-ethanol trifluoroacetate,   rac-erythro-[2-Amino-2-(4-chloro-phenyl)-1-[4-(tetrahydro-pyran-3-yloxy)-phenyl]-ethanol,   rac-erythro-[2-Amino-2-(4-chloro-phenyl)-1-(4-isopropoxy-phenyl)-ethanol hydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[5-(3-methanesulfonyl-phenyl)-pyridin-2-yl]-ethanol bistrifluoroacetate, and   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-(5′-fluoro-[3,3′]bipyridinyl-6-yl)-ethanol trihydrochloride   or a pharmaceutically active salt or ester thereof.   
     
     
         23 . The compound of  claim 2 , selected from the group consisting of
 rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[3-fluoro-5-(3-methoxy-phenyl)-pyridin-2-yl]-ethanol dihydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(5-fluoro-pyridin-3-yl)-3-methyl-phenyl]-ethanol bis-trifluoroacetate,   rac-erythro-[rac-2-Amino-2-(3,4-dichloro-phenyl)-1-[2-methyl-6-(tetrahydro-furan-3-yloxy)-pyridin-3-yl]-ethanol dihydrochloride,   rac-erythro-[rac-2-Amino-2-(3,4-dichloro-phenyl)-1-[2-fluoro-4-(tetrahydro-furan-3-yloxy)-phenyl]-ethanol hydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[2-methyl-6-(tetrahydro-pyran-4-yloxy)-pyridin-3-yl]-ethanol dihydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[3-fluoro-4-(tetrahydro-pyran-4-yloxy)-phenyl]-ethanol hydrochloride,   rac-erythro-[rac-2-Amino-2-(3,4-dichloro-phenyl)-1-[6-(tetrahydro-furan-3-yloxy)-pyridin-3-yl]-ethanol dihydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[3,5-difluoro-4-(tetrahydro-pyran-4-yloxy)-phenyl]-ethanol hydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[4-methyl-6-(tetrahydro-pyran-4-yloxy)-pyridin-3-yl]-ethanol dihydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[6-(tetrahydro-pyran-4-yloxy)-pyridin-3-yl]-ethanol dihydrochloride,   rac-erythro-[rac-2-Amino-2-(3,4-dichloro-phenyl)-1-[5-(tetrahydro-furan-3-yloxy)-pyridin-2-yl]-ethanol dihydrochloride, and   rac-erythro-[(rac)-2-Amino-2-(3,4-dichloro-phenyl)-1-[4-methyl-6-(tetrahydro-furan-3-yloxy)-pyridin-3-yl]-ethanol dihydrochloride   or a pharmaceutically active salt or ester thereof.   
     
     
         24 . The compound of  claim 2 , selected from the group consisting of
 rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[5-(tetrahydro-pyran-4-yloxy)-pyridin-2-yl]-ethanol dihydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[5-methyl-6-(tetrahydro-pyran-4-yloxy)-pyridin-3-yl]-ethanol dihydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-(6-isopropoxy-2-methyl-pyridin-3-yl)-ethanol dihydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[2-fluoro-4-(tetrahydro-furan-2-ylmethoxy)-phenyl]-ethanol, hydrochloride salt,   rac-erythro-[1-[4-[(rac)-2-Amino-2-(3,4-dichloro-phenyl)-1-hydroxy-ethyl]-3-fluoro-phenoxy]-4-chloro-butan-2-ol hydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-(6-isopropoxy-4-methyl-pyridin-3-yl)-ethanol dihydrochloride,   rac-erythro-[(rac)-2-Amino-2-(3,4-dichloro-phenyl)-1-[5-methyl-6-(tetrahydro-furan-3-yloxy)-pyridin-3-yl]-ethanol dihydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-(5-isopropoxy-pyridin-2-yl)-ethanol dihydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[2-fluoro-4-(tetrahydro-pyran-4-yloxy)-phenyl]-ethanol hydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[2-fluoro-4-(3-methyl-oxetan-3-ylmethoxy)-phenyl]-ethanol,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-(4-trimethylsilanyl-phenyl)-ethanol trifluoroacetate, and   rac-erythro-[1-Amino-2-biphenyl-4-yl-1-(4-chloro-phenyl)-propan-2-ol trifluoroacetate   or a pharmaceutically active salt or ester thereof.   
     
     
         25 . The compound of  claim 2 , selected from the group consisting of
 rac-erythro-[2-Amino-1-(4-tert-butyl-phenyl)-2-(3,4-dichloro-phenyl)-ethanol trifluoroacetate,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(1,1,2,2-tetrafluoro-ethoxy)-phenyl]-ethanol,   rac-erythro-[2-(3,4-Dichloro-phenyl)-1-[4-(5-fluoro-pyridin-3-yl)-phenyl]-2-methylamino-ethanol hydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(tetrahydro-pyran-4-yloxy)-phenyl]-ethanol,   (1R,2S or 1S,2R)-[2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(tetrahydro-pyran-4-yloxy)-phenyl]-ethanol,   rac-erythro-[rac-2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(tetrahydro-furan-3-yloxy)-phenyl]-ethanol,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-hydroxy-ethyl]-phenoxy]-2-chloromethyl-2-methyl-propan-1-ol hydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(1,1-dioxo-hexahydro-1-λ 6 -thiopyran-4-yloxy)-phenyl]-ethanol,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(tetrahydro-pyran-4-ylmethoxy)-phenyl]-ethanol,   rac-erythro-[1-(4-[4-[2-Amino-2-(3,4-dichloro-phenyl)-1-hydroxy-ethyl]-phenoxy]-piperidin-1-yl)-ethanone,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(2,2,2-trifluoro-ethoxy)-phenyl]-ethanol, and   rac-erythro-[2-Amino-2-(4-chloro-phenyl)-1-(4-cyclopentyloxy-phenyl)-ethanol hydrochloride   or a pharmaceutically active salt or ester thereof.   
     
     
         26 . The compound of  claim 2 , selected from the group consisting of
 rac-erythro-[2-Amino-1-(4-cyclopropylmethoxy-phenyl)-2-(3,4-dichloro-phenyl)-ethanol,   rac-erythro-2-Amino-2-(3,4-dichloro-phenyl)-1-(4-isobutoxy-phenyl)-ethanol,   rac-erythro-2-Amino-1-(4-sec-butoxy-phenyl)-2-(3,4-dichloro-phenyl)-ethanol,   rac-erythro-2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(3,3,3-trifluoro-propoxy)-phenyl]-ethanol,   rac-erythro-2-Amino-2-(4-chloro-phenyl)-1-(4-cyclohexyloxy-phenyl)-ethanol,   rac-erythro-[2-Amino-2-(3-chloro-4-methyl-phenyl)-1-[4-(tetrahydro-pyran-4-yloxy)-phenyl]-ethanol,   rac-erythro-[2-Amino-2-(3-chloro-4-methyl-phenyl)-1-[4-(tetrahydro-pyran-4-yloxy)-phenyl]-ethanol,   rac-erythro-2-Amino-2-(3-chloro-4-methyl-phenyl)-1-(4-isopropoxy-phenyl)-ethanol,   rac-erythro-2-Amino-2-(3-fluoro-4-methyl-phenyl)-1-[4-(tetrahydro-pyran-4-yloxy)-phenyl]-ethanol,   rac-erythro-2-Amino-2-(4-chloro-phenyl)-1-[4-(2-fluoro-1-fluoromethyl-ethoxy)-phenyl]-ethanol,   rac-erythro-2-Amino-2-(4-chloro-phenyl)-1-[4-(tetrahydro-pyran-4-yloxy)-phenyl]-ethanol, and   rac-erythro-2-Amino-2-(4-chloro-phenyl)-1-(3′-methoxymethyl-biphenyl-4-yl)-ethanol hydrochloride   or a pharmaceutically active salt or ester thereof.   
     
     
         27 . The compound of  claim 2 , selected from the group consisting of
 rac-erythro-2-Amino-2-(4-chloro-phenyl)-1-(4-pyridin-4-yl-phenyl)-ethanol,   rac-erythro-2-Amino-2-(4-chloro-phenyl)-1-(3′-methanesulfonyl-biphenyl-4-yl)-ethanol,   rac-erythro-2-Amino-2-(4-chloro-phenyl)-1-(4-pyridin-3-yl-phenyl)-ethanol hydrochloride,   rac-erythro-2-Amino-2-(4-chloro-phenyl)-1-[4-(5-methoxy-pyridin-3-yl)-phenyl]-ethanol,   rac-erythro-2-Amino-2-(4-chloro-phenyl)-1-(4-pyrimidin-5-yl-phenyl)-ethanol,   rac-erythro-2-Amino-2-(4-chloro-phenyl)-1-[4-(5-fluoro-pyridin-3-yl)-phenyl]-ethanol,   rac-erythro-N-[4′-[2-Amino-2-(4-chloro-phenyl)-1-hydroxy-ethyl]-biphenyl-3-yl]-acetamide,   rac-erythro-2-Amino-2-(4-chloro-phenyl)-1-(2′-fluoro-biphenyl-4-yl)-ethanol,   rac-erythro-2-Amino-1-[4-(6-amino-pyridin-3-yl)-phenyl]-2-(4-chloro-phenyl)-ethanol,   rac-erythro-2-Amino-2-(4-chloro-phenyl)-1-(4-thiophen-3-yl-phenyl)-ethanol,   rac-erythro-2-Amino-2-(4-chloro-phenyl)-1-(3′-methyl-biphenyl-4-yl)-ethanol, and   rac-erythro-2-Amino-2-(4-chloro-phenyl)-1-(3′-methoxy-biphenyl-4-yl)-ethanol   or a pharmaceutically active salt or ester thereof.   
     
     
         28 . The compound of  claim 2 , selected from the group consisting of
 rac-erythro-2-Amino-1-(2′-chloro-biphenyl-4-yl)-2-(4-chloro-phenyl)-ethanol,   rac-erythro-2-Amino-1-(3′-chloro-biphenyl-4-yl)-2-(4-chloro-phenyl)-ethanol,   rac-erythro-2-Amino-2-(4-chloro-phenyl)-1-[4-(2,4-dimethyl-thiazol-5-yl)-phenyl]-ethanol,   rac-erythro-2-Amino-2-(4-chloro-phenyl)-1-(2′-methyl-biphenyl-4-yl)-ethanol,   rac-erythro-2-Amino-2-(4-chloro-phenyl)-1-[4-(6-methoxy-pyridin-3-yl)-phenyl]-ethanol,   rac-erythro-2-Amino-2-(4-chloro-phenyl)-1-(3′-trifluoromethoxy-biphenyl-4-yl)-ethanol,   rac-erythro-2-Amino-2-(4-chloro-phenyl)-1-(3′-trifluoromethyl-biphenyl-4-yl)-ethanol,   rac-erythro-2-Amino-2-(4-chloro-phenyl)-1-(6-morpholin-4-yl-pyridin-3-yl)-ethanol,   rac-erythro-2-Amino-2-(3,4-dichloro-phenyl)-1-(4-pyridin-3-yl-phenyl)-ethanol,   rac-erythro-2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(5-methanesulfonyl-pyridin-3-yl)-phenyl]-ethanol,   rac-erythro-2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(5-fluoro-pyridin-3-yl)-phenyl]-ethanol, and   rac-erythro-2-Amino-2-(3,4-dichloro-phenyl)-1-(4-pyridin-3-yl-phenyl)-ethanol   or a pharmaceutically active salt or ester thereof.   
     
     
         29 . The compound of  claim 2 , selected from the group consisting of
 rac-erythro-2-Amino-2-(4-chloro-3-fluoro-phenyl)-1-[4-(5-fluoro-pyridin-3-yl)-phenyl]-ethanol,   rac-erythro-2-Amino-2-(4-chloro-3-methyl-phenyl)-1-(4-pyridin-3-yl-phenyl)-ethanol,   rac-erythro-2-Amino-1-(4-pyridin-3-yl-phenyl)-2-(4-trifluoromethyl-phenyl)-ethanol,   rac-erythro-2-Amino-2-(3,4-dichloro-phenyl)-1-(3′-dimethylamino-biphenyl-4-yl)-ethanol,   rac-erythro-2-Amino-2-(3-fluoro-4-methyl-phenyl)-1-(4-pyridin-3-yl-phenyl)-ethanol,   rac-erythro-2-Amino-2-(3-chloro-4-methyl-phenyl)-1-(4-pyridin-3-yl-phenyl)-ethanol,   rac-erythro-2-Amino-2-(3-chloro-4-methyl-phenyl)-1-[4-(5-fluoro-pyridin-3-yl)-phenyl]-ethanol,   rac-erythro-2-Amino-2-(3-fluoro-4-methyl-phenyl)-1-[4-(5-fluoro-pyridin-3-yl)-phenyl]-ethanol,   rac-erythro-2-Amino-2-(3-fluoro-4-trifluoromethyl-phenyl)-1-(4-pyridin-3-yl-phenyl)-ethanol,   rac-erythro-2-Amino-1-[4-(5-fluoro-pyridin-3-yl)-phenyl]-2-(3-fluoro-4-trifluoromethyl-phenyl)-ethanol,   rac-erythro-2-Amino-2-(4-chloro-2-fluoro-phenyl)-1-(4-pyridin-3-yl-phenyl)-ethanol, and   rac-erythro-1-(3,4-Dichloro-phenyl)-2-methoxy-2-(4-pyridin-3-yl-phenyl)-ethylamine dihydrochloride   or a pharmaceutically active salt or ester thereof.   
     
     
         30 . The compound of  claim 2 , selected from the group consisting of
 rac-erythro-[1-(3,4-Dichloro-phenyl)-2-ethoxy-2-[4-(5-fluoro-pyridin-3-yl)-phenyl]-ethylamine trifluoroacetate,   rac-erythro-2-Amino-2-(3,4-dichloro-phenyl)-1-(4-phenoxy-phenyl)-ethanol,   rac-erythro-2-Amino-2-(4-chloro-phenyl)-1-[2-fluoro-4-(2,2,3,3,3-pentafluoro-propoxy)-phenyl]-ethanol,   rac-erythro-2-Amino-2-(4-chloro-phenyl)-1-[4-(2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-ethanol,   rac-erythro-2-Amino-2-(3,4-dichloro-phenyl)-1-(3′-nitro-biphenyl-4-yl)-ethanol,   rac-erythro-4′-[2-Amino-2-(3,4-dichloro-phenyl)-1-hydroxy-ethyl]-biphenyl-3-carboxylic acid amide,   rac-erythro-2-Amino-2-(3,4-dichloro-phenyl)-1-(2′-fluoro-5′-isopropoxy-biphenyl-4-yl)-ethanol, and   rac-erythro-2-Amino-2-(3,4-dichloro-phenyl)-1-(3′-isopropoxy-biphenyl-4-yl)-ethanol,   or a pharmaceutically active salt or ester thereof.   
     
     
         31 . The compound of  claim 2 , selected from the group consisting of
 rac-erythro-[2-Amino-2-(4-chloro-phenyl)-1-[4-(tetrahydro-pyran-3-yloxy)-phenyl]-ethanol,   rac-erythro-[2-Amino-2-(4-chloro-phenyl)-1-(4-isopropoxy-phenyl)-ethanol hydrochloride,   rac-erythro-[rac-2-Amino-2-(3,4-dichloro-phenyl)-1-[2-methyl-6-(tetrahydro-furan-3-yloxy)-pyridin-3-yl]-ethanol dihydrochloride,   rac-erythro-[rac-2-Amino-2-(3,4-dichloro-phenyl)-1-[2-fluoro-4-(tetrahydro-furan-3-yloxy)-phenyl]-ethanol hydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[2-methyl-6-(tetrahydro-pyran-4-yloxy)-pyridin-3-yl]-ethanol dihydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[3-fluoro-4-(tetrahydro-pyran-4-yloxy)-phenyl]-ethanol hydrochloride,   rac-erythro-[rac-2-Amino-2-(3,4-dichloro-phenyl)-1-[6-(tetrahydro-furan-3-yloxy)-pyridin-3-yl]-ethanol dihydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[3,5-difluoro-4-(tetrahydro-pyran-4-yloxy)-phenyl]-ethanol hydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[4-methyl-6-(tetrahydro-pyran-4-yloxy)-pyridin-3-yl]-ethanol dihydrochloride, and   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[6-(tetrahydro-pyran-4-yloxy)-pyridin-3-yl]-ethanol dihydrochloride   or a pharmaceutically active salt or ester thereof.   
     
     
         32 . The compound of  claim 2 , selected from the group consisting of
 rac-erythro-[rac-2-Amino-2-(3,4-dichloro-phenyl)-1-[5-(tetrahydro-furan-3-yloxy)-pyridin-2-yl]-ethanol dihydrochloride,   rac-erythro-[(rac)-2-Amino-2-(3,4-dichloro-phenyl)-1-[4-methyl-6-(tetrahydro-furan-3-yloxy)-pyridin-3-yl]-ethanol dihydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[5-(tetrahydro-pyran-4-yloxy)-pyridin-2-yl]-ethanol dihydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[5-methyl-6-(tetrahydro-pyran-4-yloxy)-pyridin-3-yl]-ethanol dihydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-(6-isopropoxy-2-methyl-pyridin-3-yl)-ethanol dihydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[2-fluoro-4-(tetrahydro-furan-2-ylmethoxy)-phenyl]-ethanol, hydrochloride salt,   rac-erythro-[1-[4-[(rac)-2-Amino-2-(3,4-dichloro-phenyl)-1-hydroxy-ethyl]-3-fluoro-phenoxy]-4-chloro-butan-2-ol hydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-(6-isopropoxy-4-methyl-pyridin-3-yl)-ethanol dihydrochloride,   rac-erythro-[(rac)-2-Amino-2-(3,4-dichloro-phenyl)-1-[5-methyl-6-(tetrahydro-furan-3-yloxy)-pyridin-3-yl]-ethanol dihydrochloride, and   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-(5-isopropoxy-pyridin-2-yl)-ethanol dihydrochloride   or a pharmaceutically active salt or ester thereof.   
     
     
         33 . The compound of  claim 2 , selected from the group consisting of
 rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[2-fluoro-4-(tetrahydro-pyran-4-yloxy)-phenyl]-ethanol hydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[2-fluoro-4-(3-methyl-oxetan-3-ylmethoxy)-phenyl]-ethanol,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(1,1,2,2-tetrafluoro-ethoxy)-phenyl]-ethanol,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(tetrahydro-pyran-4-yloxy)-phenyl]-ethanol,   (1R,2S or 1S,2R)-[2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(tetrahydro-pyran-4-yloxy)-phenyl]-ethanol,   rac-erythro-[rac-2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(tetrahydro-furan-3-yloxy)-phenyl]-ethanol,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-hydroxy-ethyl]-phenoxy]-2-chloromethyl-2-methyl-propan-1-ol hydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(1,1-dioxo-hexahydro-1-λ 6 -thiopyran-4-yloxy)-phenyl]-ethanol,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(tetrahydro-pyran-4-ylmethoxy)-phenyl]-ethanol, and   rac-erythro-[1-(4-[4-[2-Amino-2-(3,4-dichloro-phenyl)-1-hydroxy-ethyl]-phenoxy]-piperidin-1-yl)-ethanone   or a pharmaceutically active salt or ester thereof.   
     
     
         34 . The compound of  claim 2 , selected from the group consisting of
 rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(2,2,2-trifluoro-ethoxy)-phenyl]-ethanol,   rac-erythro-[2-Amino-2-(4-chloro-phenyl)-1-(4-cyclopentyloxy-phenyl)-ethanol hydrochloride,   rac-erythro-[2-Amino-1-(4-cyclopropylmethoxy-phenyl)-2-(3,4-dichloro-phenyl)-ethanol,   rac-erythro-2-Amino-2-(3,4-dichloro-phenyl)-1-(4-isobutoxy-phenyl)-ethanol,   rac-erythro-2-Amino-1-(4-sec-butoxy-phenyl)-2-(3,4-dichloro-phenyl)-ethanol,   rac-erythro-2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(3,3,3-trifluoro-propoxy)-phenyl]-ethanol,   rac-erythro-2-Amino-2-(4-chloro-phenyl)-1-(4-cyclohexyloxy-phenyl)-ethanol,   rac-erythro-[2-Amino-2-(3-chloro-4-methyl-phenyl)-1-[4-(tetrahydro-pyran-4-yloxy)-phenyl]-ethanol, and   rac-erythro-[2-Amino-2-(3-chloro-4-methyl-phenyl)-1-[4-(tetrahydro-pyran-4-yloxy)-phenyl]-ethanol,   or a pharmaceutically active salt or ester thereof.   
     
     
         35 . The compound of  claim 2 , selected from the group consisting of
 rac-erythro-[rac-2-Amino-2-(3,4-dichloro-phenyl)-1-[2-methyl-6-(tetrahydro-furan-3-yloxy)-pyridin-3-yl]-ethanol dihydrochloride,   (1R,2S or 1S,2R)-[2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(tetrahydro-pyran-4-yloxy)-phenyl]-ethanol,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[2-fluoro-4-(3-methyl-oxetan-3-ylmethoxy)-phenyl]-ethanol,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[2-fluoro-4-(tetrahydro-pyran-4-yloxy)-phenyl]-ethanol hydrochloride,   rac-erythro-[rac-2-Amino-2-(3,4-dichloro-phenyl)-1-[2-fluoro-4-(tetrahydro-furan-3-yloxy)-phenyl]-ethanol hydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[2-methyl-6-(tetrahydro-pyran-4-yloxy)-pyridin-3-yl]-ethanol dihydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[3-fluoro-4-(tetrahydro-pyran-4-yloxy)-phenyl]-ethanol hydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(tetrahydro-pyran-4-yloxy)-phenyl]-ethanol,   rac-erythro-[rac-2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(tetrahydro-furan-3-yloxy)-phenyl]-ethanol,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-hydroxy-ethyl]-phenoxy]-2-chloromethyl-2-methyl-propan-1-ol hydrochloride,   rac-erythro-2-Amino-2-(4-chloro-phenyl)-1-[4-(tetrahydro-pyran-4-yloxy)-phenyl]-ethanol,   rac-erythro-[rac-2-Amino-2-(3,4-dichloro-phenyl)-1-[6-(tetrahydro-furan-3-yloxy)-pyridin-3-yl]-ethanol dihydrochloride,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[4-(1,1-dioxo-hexahydro-1-λ 6 -thiopyran-4-yloxy)-phenyl]-ethanol,   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[3,5-difluoro-4-(tetrahydro-pyran-4-yloxy)-phenyl]-ethanol hydrochloride, and   rac-erythro-[2-Amino-2-(3,4-dichloro-phenyl)-1-[4-methyl-6-(tetrahydro-pyran-4-yloxy)-pyridin-3-yl]-ethanol dihydrochloride,   or a pharmaceutically active salt or ester thereof.   
     
     
         36 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula I 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is hydrogen, halogen or lower alkyl, 
         R 2  is hydrogen, halogen or lower alkyl, 
         R 3  is halogen or lower alkyl, which lower alkyl is optionally substituted by halogen, 
         R 4  is a) lower alkyl, optionally substituted by halogen or lower alkoxy,
 b) lower alkoxy, optionally substituted by halogen, hydroxyl, cycloalkyl or heterocyclyl, 
 c) —Si(lower alkyl) 3 , 
 d) —O-cycloalkyl, optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, 
 e) —O-aryl, optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, 
 f) —O-heteroaryl, optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, 
 g) —O-heterocyclyl, optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl,
 wherein each S being part of a heterocyclyl is optionally substituted by oxo, 
 
 h) heteroaryl, optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, 
 i) aryl, substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, or 
 j) heterocyclyl, optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, 
 and R 4  is hydrogen when R 10  is phenyl, wherein the phenyl is optionally substituted by halogen, lower alkyl, or —S(O) 2 -lower alkyl, 
 and when R 6  is lower alkyl, R 4  is 
 a) lower alkyl, optionally substituted by halogen or lower alkoxy, 
 b) lower alkoxy, optionally substituted by halogen, hydroxyl, cycloalkyl or heterocyclyl, 
 c) —Si(lower alkyl) 3 , 
 d) —O-cycloalkyl, optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, 
 e) —O-aryl, optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, 
 f) —O-heteroaryl, optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, 
 g) —O-heterocyclyl, optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, 
 wherein each S being part of a heterocyclyl is optionally substituted by oxo, 
 h) heteroaryl, optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, 
 i) aryl, optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, 
 j) heterocyclyl, optionally substituted by halogen, amido, nitro, acetyl, acetamidyl, lower alkyl, halogen-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, halogen-lower alkoxy, —NR 11 R 12 , or —S(O) 2 -lower alkyl, 
 
         R 5  is halogen or lower alkyl, 
         R 6  is hydrogen or lower alkyl, 
         R 7  is hydrogen or lower alkyl, 
         R 8  is hydrogen or lower alkyl, 
         R 9  is hydrogen, halogen, lower alkyl or lower alkoxy, 
         R 10  is hydrogen, halogen, lower alkyl or lower alkoxy, 
         R 11  is hydrogen or lower alkyl, 
         R 12  is hydrogen or lower alkyl, 
         X is a) N and Y is C—R 10 ,
 b) C—R 9  and Y is N, or 
 c) C—R 9  and Y is C—R 10 , and 
 
         n is 0 or 1, 
         with the proviso that R 8  is lower alkyl, when 
         i) R 1  is hydrogen, R 2  is hydrogen, R 3  is methyl, R 4  is methyl, R 6  is hydrogen, R 7  is hydrogen, R 9  is hydrogen, R 10  is hydrogen, n is 0, X is C—R 9  and Y is C—R 10 ; 
         j) R 1  is hydrogen, R 2  is hydrogen, R 3  is methyl, R 4  is methyl, R 6  is hydrogen, R 7  is ethyl, R 9  is methyl, R 10  is hydrogen, n is 0, X is C—R 9  and Y is C—R 10 ; 
         k) R 1  is hydrogen, R 2  is hydrogen, R 3  is t-butyl, R 4  is t-butyl, R 6  is hydrogen, R 7  is hydrogen, R 9  is hydrogen, R 10  is hydrogen, n is 0, X is C—R 9  and Y is C—R 10 ; 
         l) R 1  is hydrogen, R 2  is hydrogen, R 3  is chloro, R 4  is hydrogen, R 6  is hydrogen, R 7  is hydrogen, R 9  is hydrogen, R 10  is hydrogen, n is 0, X is C—R 9  and Y is C—R 10 ; 
         m) R 1  is hydrogen, R 2  is hydrogen, R 3  is chloro, R 4  is morpholino, R 6  is hydrogen, R 7  is hydrogen, R 9  is hydrogen, R 10  is hydrogen, n is 0, X is C—R 9  and Y is C—R 10 ; 
         n) R 1  is hydrogen, R 2  is hydrogen, R 3  is chloro, R 4  is hydrogen, R 6  is hydrogen, R 7  is hydrogen, R 9  is chloro, R 10  is hydrogen, n is 0, X is C—R 9  and Y is C—R 10 ; 
         o) R 1  is hydrogen, R 2  is hydrogen, R 3  is chloro, R 4  is hydrogen, R 6  is methyl, R 7  is hydrogen, R 9  is hydrogen, n is 0, X is C—R 9  and Y is N; or 
         p) R 1  is hydrogen, R 2  is hydrogen, R 3  is chloro, R 4  is hydrogen, R 6  is methyl, R 7  is hydrogen, R 10  is hydrogen, n is 0, X is N and Y is C—R 10 ; 
         or a pharmaceutically active salt or ester thereof and a pharmaceutically acceptable carrier.

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