Amino alcohol compounds

Abstract

A method for the preventing a disease selected from the group consisting of rheumatoid arthritis and psoriasis in a mammal, such as a human, in need thereof, which includes administering to the mammal a pharmaceutically effective amount of a compound of formula (Ia) wherein R 1 and R 2 are each hydrogen; R 3 is hydrogen; R 4 is C 1 -C 2 alkyl; n is 2; X is=N-D, wherein D is hydrogen, C 1 -C 4 alkyl or phenyl; Y is ethylene, ethynylene, —CO—CH 2 or phenylene; Z is ethylene or trimethylene; R 5 is an unsubstituted C 3 -C 10 cycloalkyl, an unsubstituted C 6 -C 10 aryl, or a C 3 -C 10 cycloalkyl or C 6 -C 10 aryl substituted with 1 to 3 substituents selected from the group consisting of halogen, lower alkyl, halogeno lower alkyl and lower alkoxy; and R 6 and R 7 are each hydrogen.

1 . A method for the prevention of a disease selected from the group consisting of rheumatoid arthritis and psoriasis in a human in need thereof, which comprises administering to said human a pharmaceutically effective amount of a compound of formula (Ia)  
     
       
         
         
             
             
         
       
       wherein R 1  and R 2  are each a hydrogen atom;  
       R 3  is a hydrogen atom;  
       R 4  is a C 1 -C 2  alkyl group;  
       n is 2;  
       X is=N-D, wherein D is a hydrogen atom, a C 1 -C 4  alkyl group or a phenyl group;  
       Y is an ethylene group, an ethynylene group, a group of a formula —CO—CH 2  or a phenylene group;  
       Z is an ethylene group or a trimethylene group;  
       R 5 is an unsubstituted C 3 -C 10  cycloalkyl group, an unsubstituted C 6 -C 10  aryl group, or a C 3 -C 10  cycloalkyl group or a C 6 -C 10  aryl group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group and a lower alkoxy group; and  
       R 6  and R 7  are each a hydrogen atom;  
       or a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof.  
     
   
   
       2 . The method according to  claim 1 , wherein, in the compound, R 4  is a methyl group, or a pharmacologically acceptable salt thereof.  
   
   
       3 . The method according to  claim 2 , wherein, in the compound, X is a group of a formula ═N—CH 3 , or a pharmacologically acceptable salt thereof.  
   
   
       4 . The method according to  claim 1 , wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol, or a pharmacologically acceptable salt thereof.  
   
   
       5 . The method according to  claim 1 , wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol, or a pharmacologically acceptable salt thereof.  
   
   
       6 . The method according to  claim 1 , wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol, or a pharmacologically acceptable salt thereof.  
   
   
       7 . The method according to  claim 1 , wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(4-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol.  
   
   
       8 . The method according to  claim 1 , wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(4-methylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol.  
   
   
       9 . The method according to  claim 1 , wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(4-methoxyphenyl)butanoyl]pyrrol-2-yl}butan-1-ol.  
   
   
       10 . The method according to  claim 1 , wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3-methylphenyl)butyl]pyrrol-2-yl}butan-1-ol.  
   
   
       11 . The method according to  claim 1 , wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butyl]pyrrol-2-yl}butan-1-ol.  
   
   
       12 . The method according to  claim 1 , wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butyl]pyrrol-2-yl}butan-1-ol.  
   
   
       13 . The method according to  claim 1 , wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3-triflouromethylphenyl)butyl]pyrrol-2-yl}butan-1-ol.  
   
   
       14 . The method according to  claim 1 , wherein R 1 , R 2  and R 3  are each a hydrogen atom, R 4  is a methyl group, n is 2 and Y-Z-R 5  is —O—(CH 2 ) 3 -(4-F-phenyl).  
   
   
       15 . The method according to  claim 1 , wherein the compound is selected from the group consisting of 
 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol;    2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol;    2-amino-2-methyl-4-{1-methyl-5-[4-(3-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol;    2-amino-2-methyl-4-{1-methyl-5-[4-(4-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol;    2-amino-2-methyl-4-{1-methyl-5-[4-(4-methylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol;    2-amino-2-methyl-4-{1-methyl-5-[4-(4-methoxyphenyl)butanoyl]pyrrol-2-yl}butan-1-ol;    2-amino-2-methyl-4-{1-methyl-5-[4-(3-methylphenyl)butyl]pyrrol-2-yl}butan-1-ol;    2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butyl]pyrrol-2-yl}butan-1-ol;    2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butyl]pyrrol-2-yl}butan-1-ol;    2-amino-2-methyl-4-{-methyl-5-[4-(3-triflouromethylphenyl)butyl]pyrrol-2-yl}butan-1-ol; and    a compound of the formula (Ia), wherein R 1 , R 2  and R 3  are each a hydrogen atom, R 4  is a methyl group, n is 2 and Y-Z-R 5  is —CO—(CH 2 ) 3 -(4-F-phenyl),    or a pharmacologically acceptable salt thereof.    
   
   
       16 . The method according to  claim 4 , wherein the configuration at the carbon atom to which the group of the formula —NR 1 R 2  attaches is the R configuration, or a pharmacologically acceptable salt thereof.  
   
   
       17 . The method according to  claim 5 , wherein the configuration at the carbon atom to which the group of the formula —NR 1 R 2  attaches is the R configuration, or a pharmacologically acceptable salt thereof.  
   
   
       18 . The method according to  claim 6 , wherein the configuration at the carbon atom to which the group of the formula —NR 1 R 2  attaches is the R configuration, or a pharmacologically acceptable salt thereof.  
   
   
       19 . The method according to  claim 7 , wherein the configuration at the carbon atom to which the group of the formula —NR 1 R 2  attaches is the R configuration, or a pharmacologically acceptable salt thereof.  
   
   
       20 . The method according to  claim 8 , wherein the configuration at the carbon atom to which the group of the formula —NR 1 R 2  attaches is the R configuration, or a pharmacologically acceptable salt thereof.  
   
   
       21 . The method according to  claim 9 , wherein the configuration at the carbon atom to which the group of the formula —NR 1 R 2  attaches is the R configuration, or a pharmacologically acceptable salt thereof.  
   
   
       22 . The method according to  claim 10 , wherein the configuration at the carbon atom to which the group of the formula —NR 1 R 2  attaches is the R configuration, or a pharmacologically acceptable salt thereof.  
   
   
       23 . The method according to  claim 11 , wherein the configuration at the carbon atom to which the group of the formula —NR 1 R 2  attaches is the R configuration, or a pharmacologically acceptable salt thereof.  
   
   
       24 . The method according to  claim 12 , wherein the configuration at the carbon atom to which the group of the formula —NR 1 R 2  attaches is the R configuration, or a pharmacologically acceptable salt thereof.  
   
   
       25 . The method according to  claim 13 , wherein the configuration at the carbon atom to which the group of the formula —NR 1 R 2  attaches is the R configuration, or a pharmacologically acceptable salt thereof.  
   
   
       26 . The method according to  claim 14 , wherein the configuration at the carbon atom to which the group of the formula —NR 1 R 2  attaches is the R configuration, or a pharmacologically acceptable salt thereof.  
   
   
       27 . The method according to  claim 1 , wherein the disease is rheumatoid arthritis.  
   
   
       28 . The method according to  claim 1 , wherein the disease is psoriasis.  
   
   
       29 . A method for the prevention of a disease selected from the group consisting of rheumatoid arthritis and psoriasis in a mammal in need thereof, which comprises administering to said mammal a pharmaceutically effective amount of a compound of formula (Ia)  
     
       
         
         
             
             
         
       
       wherein R 1  and R 2  are each a hydrogen atom;  
       R 3  is a hydrogen atom;  
       R 4  is a C 1 -C 2  alkyl group;  
       n is 2;  
       X is=N-D, wherein D is a hydrogen atom, a C 1 -C 4  alkyl group or a phenyl group;  
       Y is an ethylene group, an ethynylene group, a group of a formula —CO—CH 2  or a phenylene group;  
       Z is an ethylene group or a trimethylene group;  
       R 5 is an unsubstituted C 3 -C 10  cycloalkyl group, an unsubstituted C 6 -C 10  aryl group, or a C 3 -C 10  cycloalkyl group or a C 6 -C 10  aryl group substituted with from 1 to 3 substituents selected from the group consisting of a halogen atom, a lower alkyl group, a halogeno lower alkyl group and a lower alkoxy group; and  
       R 6  and R 7  are each a hydrogen atom;  
       or a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof.  
     
   
   
       30 . The method according to  claim 29 , wherein, in the compound, R 4  is a methyl group, or a pharmacologically acceptable salt thereof.  
   
   
       31 . The method according to  claim 30 , wherein, in the compound, X is a group of a formula ═N—CH 3 , or a pharmacologically acceptable salt thereof.  
   
   
       32 . The method according to  claim 29 , wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol, or a pharmacologically acceptable salt thereof.  
   
   
       33 . The method according to  claim 29 , wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol, or a pharmacologically acceptable salt thereof.  
   
   
       34 . The method according to  claim 29 , wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol, or a pharmacologically acceptable salt thereof.  
   
   
       35 . The method according to  claim 29 , wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(4-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol.  
   
   
       36 . The method according to  claim 29 , wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(4-methylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol.  
   
   
       37 . The method according to  claim 29 , wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(4-methoxyphenyl)butanoyl]pyrrol-2-yl}butan-1-ol.  
   
   
       38 . The method according to  claim 29 , wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3-methylphenyl)butyl]pyrrol-2-yl}butan-1-ol.  
   
   
       39 . The method according to  claim 29 , wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butyl]pyrrol-2-yl}butan-1-ol.  
   
   
       40 . The method according to  claim 29 , wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butyl]pyrrol-2-yl}butan-1-ol.  
   
   
       41 . The method according to  claim 29 , wherein said compound is 2-amino-2-methyl-4-{1-methyl-5-[4-(3-triflouromethylphenyl)butyl]pyrrol-2-yl}butan-1-ol.  
   
   
       42 . The method according to  claim 29 , wherein R 1 , R 2  and R 3  are each a hydrogen atom, R 4  is a methyl group, n is 2 and Y-Z-R 5  is —O—(CH 2 ) 3 -(4-F-phenyl).  
   
   
       43 . The method according to  claim 29 , wherein the compound is selected from the group consisting of 
 2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol;    2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol;    2-amino-2-methyl-4-{1-methyl-5-[4-(3-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol;    2-amino-2-methyl-4-{1-methyl-5-[4-(4-trifluoromethylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol;    2-amino-2-methyl-4-{1-methyl-5-[4-(4-methylphenyl)butanoyl]pyrrol-2-yl}butan-1-ol;    2-amino-2-methyl-4-{1-methyl-5-[4-(4-methoxyphenyl)butanoyl]pyrrol-2-yl}butan-1-ol;    2-amino-2-methyl-4-{1-methyl-5-[4-(3-methylphenyl)butyl]pyrrol-2-yl}butan-1-ol;    2-amino-2-methyl-4-{1-methyl-5-[4-(3,4-dimethylphenyl)butyl]pyrrol-2-yl}butan-1-ol;    2-amino-2-methyl-4-{1-methyl-5-[4-(3,5-dimethylphenyl)butyl]pyrrol-2-yl}butan-1-ol;    2-amino-2-methyl-4-{1-methyl-5-[4-(3-triflouromethylphenyl)butyl]pyrrol-2-yl}butan-1-ol; and    a compound of the formula (Ia), wherein R 1 , R 2  and R 3  are each a hydrogen atom, R 4  is a methyl group, n is 2 and Y-Z-R 5  is —O—(CH 2 ) 3 -(4-F-phenyl),    or a pharmacologically acceptable salt thereof.    
   
   
       44 . The method according to  claim 32 , wherein the configuration at the carbon atom to which the group of the formula —NR 1 R 2  attaches is the R configuration, or a pharmacologically acceptable salt thereof.  
   
   
       45 . The method according to  claim 33 , wherein the configuration at the carbon atom to which the group of the formula —NR 1 R 2  attaches is the R configuration, or a pharmacologically acceptable salt thereof.  
   
   
       46 . The method according to  claim 34 , wherein the configuration at the carbon atom to which the group of the formula —NR 1 R 2  attaches is the R configuration, or a pharmacologically acceptable salt thereof.  
   
   
       47 . The method according to  claim 35 , wherein the configuration at the carbon atom to which the group of the formula —NR 1 R 2  attaches is the R configuration, or a pharmacologically acceptable salt thereof.  
   
   
       48 . The method according to  claim 36 , wherein the configuration at the carbon atom to which the group of the formula —NR 1 R 2  attaches is the R configuration, or a pharmacologically acceptable salt thereof.  
   
   
       49 . The method according to  claim 37 , wherein the configuration at the carbon atom to which the group of the formula —NR 1 R 2  attaches is the R configuration, or a pharmacologically acceptable salt thereof.  
   
   
       50 . The method according to  claim 38 , wherein the configuration at the carbon atom to which the group of the formula —NR 1 R 2  attaches is the R configuration, or a pharmacologically acceptable salt thereof.  
   
   
       51 . The method according to  claim 39 , wherein the configuration at the carbon atom to which the group of the formula —NR 1 R 2  attaches is the R configuration, or a pharmacologically acceptable salt thereof.  
   
   
       52 . The method according to  claim 40 , wherein the configuration at the carbon atom to which the group of the formula —NR 1 R 2  attaches is the R configuration, or a pharmacologically acceptable salt thereof.  
   
   
       53 . The method according to  claim 41 , wherein the configuration at the carbon atom to which the group of the formula —NR 1 R 2  attaches is the R configuration, or a pharmacologically acceptable salt thereof.  
   
   
       54 . The method according to  claim 42 , wherein the configuration at the carbon atom to which the group of the formula —NR 1 R 2  attaches is the R configuration, or a pharmacologically acceptable salt thereof.  
   
   
       55 . The method according to  claim 29 , wherein the disease is rheumatoid arthritis.  
   
   
       56 . The method according to  claim 29 , wherein the disease is psoriasis.