Substituted benzamides

Abstract

The invention relates to compounds of formula wherein R, R 1 , R 2 , X, and Y are as defined herein and to a pharmaceutically suitable acid addition salt thereof. Compounds of formula I have a good affinity to the trace amine associated receptors (TAARs), especially for TAAR1. The compounds can be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson's disease, neurodegenerative disorders such as Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

1 . A compound of formula I 
       
         
           
           
               
               
           
         
         wherein 
         R is hydrogen or lower alkyl, 
         R 1  is —(CH 2 ) n —(O) o -heterocycloalkyl or —C(O)-heterocycloalkyl, wherein the heterocycloalkyl group is optionally substituted by lower alkyl, hydroxy, halogen or by —(CH 2 ) p -aryl; 
         n is 0, 1 or 2; 
         o is 0 or 1; 
         p is 0, 1 or 2; 
         R 2  is CF 3 , cycloalkyl, optionally substituted by lower alkoxy or halogen, or is indan-2-yl, or is heterocycloalkyl, optionally substituted by heteroaryl,
 or is aryl or heteroaryl, wherein the aromatic rings of the aryl or heteroaryl are optionally substituted by one or two substituents, selected from lower alkyl, halogen, heteroaryl, hydroxy, CF 3 , OCF 3 , OCH 2 CF 3 , OCH 2 -cycloalkyl, OCH 2 C(CH 2 OH)(CH 2 Cl)(CH 3 ), S-lower alkyl, lower alkoxy, CH 2 -lower alkoxy, lower alkynyl or cyano, or by —C(O)-phenyl, —O-phenyl, —O—CH 2 -phenyl, phenyl or —CH 2 -phenyl, and wherein the phenyl rings are optionally substituted by halogen, —C(O)-lower alkyl, —C(O)OH or —C(O)O-lower alkyl, or the aromatic rings are optionally substituted by heterocycloalkyl, OCH 2 -oxetan-3-yl or O-tetrahydropyran-4-yl, optionally substituted by lower alkyl; 
 
         X is a bond, —NR′—, —CH 2 NH—, —CHR″—, —(CHR″) q —O—, —O—(CHR″) q — or —(CH 2 ) 2 —; 
         Y is a bond or —CH 2 — 
         R′ is hydrogen or lower alkyl, 
         R″ is hydrogen, lower alkyl, CF 3 , lower alkoxy, 
         q is 0, 1, 2 or 3; 
         or a pharmaceutically suitable acid addition salt thereof. 
       
     
     
         2 . The compound of  claim 1 , wherein X is NR′ and R′ is hydrogen. 
     
     
         3 . The compound of  claim 2 , selected from the group consisting of
 (RS)-1-(4-Butyl-2-methyl-phenyl)-3-(4-pyrrolidin-3-yl-phenyl)-urea;   1-(3,4-Dichloro-phenyl)-3-[4-(4-methyl-piperazin-1-yl)-phenyl]-urea;   (RS)-1-(3,4-Dichloro-phenyl)-3-(4-pyrrolidin-3-yl-phenyl)-urea;   (RS)-1-(4-Chloro-phenyl)-3-(4-pyrrolidin-3-yl-phenyl)-urea;   (RS)-1-Phenyl-3-(4-pyrrolidin-3-yl-phenyl)-urea;   (RS)-1-(2,4-Dichloro-phenyl)-3-(4-pyrrolidin-3-yl-phenyl)-urea;   (RS)-1-(3-Chloro-phenyl)-3-(4-pyrrolidin-3-yl-phenyl)-urea;   (RS)-1-(4-Pyrrolidin-3-yl-phenyl)-3-(4-trifluoromethyl-phenyl)-urea;   (RS)-1-(5-Chloro-pyridin-2-yl)-3-(4-pyrrolidin-3-yl-phenyl)-urea;   (RS)-1-(6-Chlor-pyridin-3-yl)-3-(4-piperidin-3-yl-phenyl)-urea;   (RS)-1-(5-Chloro-pyridin-2-yl)-3-(4-piperidin-3-yl-phenyl)-urea; and   (RS)-1-(5-Chloro-pyridin-2-yl)-3-[4-(2-pyrrolidin-3-yl-ethyl)-phenyl]-urea.   
     
     
         4 . The compound of  claim 2 , selected form the group consisting of
 (RS)-1-(4-Chloro-phenyl)-3-[4-(2-pyrrolidin-3-yl-ethyl)-phenyl]-urea;   (RS)-1-(4-Chloro-phenyl)-3-[4 (2-piperidin-3-yl-ethyl)-phenyl]-urea;   (RS)-1-(4-(Morpholin-2-yl)phenyl)-3-(4-(trifluoromethyl)phenyl)urea;   (RS)-1-(4-Chiorophenyl)-3-(4-(morpholin-2-yl)phenyl)urea;   (RS)-1-(4-(Morpholin-2-yl)phenyl)-3-p-tolylurea;   (RS)-1-(6-Chloropyridin-3-yl)-3-(4-(morpholin-2-yl)phenyl)urea;   (RS)-1-(3-Chlorophenyl)-3-(4-(morpholin-2-yl)phenyl)urea;   (RS)-1-(4-(Morpholin-2-yl)phenyl)-3-m-tolylurea;   (RS)-1-(2-Chlorophenyl)-3-(4-(morpholin-2-yl)phenyl)urea;   (RS)-1-(4-Methylbenzyl)-3-(4-(morpholin-2-yl)phenyl)urea;   (R)-1-(4-(Morpholin-2-yl)phenyl)-3-(4-(trifluoromethyl)phenyl)urea; and   (S)-1-(4-(Morpholin-2-yl)phenyl)-3-(4-(trifluoromethyl)phenyl)urea.   
     
     
         5 . The compound of  claim 1 , wherein X is a bond. 
     
     
         6 . The compound of  claim 5 , selected from the group consisting of
 (RS)—N-(4-Pyrrolidin-3-yl-phenyl)-benzamide;   (RS)-4-Chloro-N-(4-pyrrolidin-3-yl-phenyl)-benzamide;   (RS)—N-(4-Pyrrolidin-3-yl-phenyl)-4-trifluoromethyl-benzamide;   (RS)-2,4-Dichloro-N-(4-pyrolidin-3-yl-phenyl)-benzamide;   (RS)-3-Chloro-N-(4-pyrrolidin-3-yl-phenyl)-benzamide;   (RS)-4-Chloro-N-[4-(1-methyl-pyrrolidin-3-yl)-phenyl]-benzamide;   (RS)-4-Chloro-N-[4-(1-ethyl-pyrrolidin-3-yl)-phenyl]-benzamide;   (RS)-4-Chloro-N-[4-(pyrrolidin-3-yloxy)-phenyl]-benzamide;   (RS)-5-Chloro-pyridine-2-carboxylic acid (4-pyrrolidin-3-yl-phenyl)-amide; and   (RS)-6-Chloro-pyridine-3-carboxylic acid (4-pyrrolidin-3 yl-phenyl)-amide.   
     
     
         7 . The compound of  claim 5 , selected from the group consisting of
 (RS)-4 Ethoxy-N-(4-pyrrolidin-3-yl-phenyl)-benzamide;   (RS)-4 Propyl N-(4-pyrrolidin-3-yl-phenyl)-benzamide;   (RS)-4-Ethynyl-N-(4-pyrrolidin-3-yl-phenyl)-benzamide;   (RS)-4-Cyano-N-(4-pyrrolidin-3-yl-phenyl)-benzamide;   (RS)-3,4-Dichloro-N-(4-pyrrolidin-3-yl-phenyl)-benzamide;   4-Chloro-N-(4-piperidin-4-yl-phenyl)-benzamide;   (RS)-4-Chloro-N-(4-piperidin-3-yl-phenyl)-benzamide;   4-Chloro-N-(4-piperazin-1-yl-phenyl)-benzamide,   4-Chloro-N-[4-((3RS,4RS)-4-fluoro-pyrrolidin-3-yl)-phenyl]-benzamide; and   (RS)-4-Chloro-N-[3-(pyrrolidin-3-yloxy)-phenyl]-benzamide.   
     
     
         8 . The compound of  claim 5 , selected from the group consisting of
 (RS)-6-Pyrazol-1-yl-N-(4-pyrrolidin-3-yl-phenyl)-nicotinamide;   (RS)-6-Chloro-N-(4-piperidin-3-yl-phenyl)-nicotinamide;   (RS)-4-Chloro-2 fluoro-N-(4-pyrrolidin-3-yl-phenyl)-benzamide;   (RS)-5-Chloro-pyridine-2-carboxylic acid (4-piperidin-3-yl-phenyl)-amide;   (RS) 4-Chloro-N-[4-(4-methyl-morpholin-2-yl)-phenyl]-benzamide;   (RS)-Quinoline-2-carboxylic acid (4-pyrrolidin-3-yl-phenyl)-amide;   (RS)-Isoquinoline-1-carboxylic acid (4-pyrrolidin-3-yl-phenyl)-amide;   (RS)-4-Chloro-pyridine-2-carboxylic acid (4-pyrrolidin-3-yl-phenyl)-amide;   (RS)-5-Bromo-pyridine-2-carboxylic acid (4-pyrrolidin-3-yl-phenyl)-amide; and   (RS)-2-Fluoro-4-methoxy-N-(4-pyrrolidin-3-yl-phenyl)benzamide.   
     
     
         9 . The compound of  claim 5 , selected from the group consisting of
 (RS)—N-(4-Pyrrolidin-3-yl-phenyl)-6-(2,2,2-trifluoro-ethoxy)-nicotinamide;   (RS)-6-Methoxy-quinoline-2-carboxylic acid (4-pyrrolidin-3-yl-phenyl)-amide;   (RS)-3-Chloro-N-(4-piperidin-3-yl-phenyl)-benzamide;   (RS)-3,4-Dichloro-N-(4-piperidin-3-yl-phenyl)-benzamide;   (RS)-4-Ethoxy-N-(4-piperidin-3-yl-phenyl)-benzamide;   (RS)—N-(4-Piperidin-3-yl-phenyl)-4-trifluoromethyl-benzamide;   (RS)-4-Chloro-2-fluoro-N-(4-piperidin-3-yl-phenyl)-benzamide;   (RS)-4-Chloro-N-(4-pyrrolidin-2-yl methyl-phenyl)-benzamide;   (RS)-1-Chloro-isoquinoline-3-carboxylic acid (4-pyrrolidin-3-yl-phenyl)-amide; and   (RS)-4-Chloro-N-[4-(2-pyrrolidin-3-yl-ethyl)-phenyl]-benzamide.   
     
     
         10 . The compound of  claim 5 , selected from the group consisting of
 (RS)-4-Chloro-N-[4-(2-piperidin-3-yl-thiyl)-phenyl]-benzamide;   4-Chloro-N—((R)-4-piperidin-3-yl-phenyl)-benzamide;   (RS)-5-Chloro-pyridine-2-carboxylic acid [4-(2-pyrrolidin-3-yl-ethyl)-phenyl]-amide;   (RS)—N-(4-Piperidin-3-yl-phenyl)-4-propyl-benzamide;   (RS)-5-Trifluoromethyl-pyridine-2-carboxylic acid (4-piperidin-3-yl-phenyl)-amide;   (RS)-5-Trifluoromethyl-pyridine-2-carboxylic acid (4-pyrrolidin-3-yl-phenyl)-amide;   (RS)-5-Trifluoromethyl-pyridine-2-carboxylic acid (4-morpholin-2-yl-phenyl)-amide;   (RS)-4-Chloro-N-[4-(2-pyrrolidin-2-yl-ethyl)-phenyl]-benzamide;   4-Chloro-N—((R)-4-morpholin-2-yl-phenyl)-benzamide; and   4-Chloro-N—((S)-4-morpholin-2-yl-phenyl)-benzamide.   
     
     
         11 . The compound of  claim 5 , selected from the group consisting of
 (RS)-4-Chloro-N-[4-(pyrrolidin-3-yloxymethyl)-phenyl]-benzamide;   (RS)-4-Chloro-2-fluoro-N-(4-morpholin-2-yl-phenyl)-benzamide;   (RS)-3,4-Dichloro-N-(4-morpholin-2-yl-phenyl)-benzamide;   (RS)-5-Chloro-pyridine-2-carboxylic acid (4-morpholin-2-yl-phenyl)-amide;   (RS)-4-Chloro-N-(4-pyrrolidin-3-ylmethyl-phenyl)-benzamide;   3,4-Dichloro-N—((R)-4-piperidin-3-yl-phenyl)-benzamide;   (R)-3-Chloro-N-(4-(piperidin-3-yl)phenyl)benzamide;   3,4-Dichloro-N—((S)-4-piperidin-3-yl-phenyl)-benzamide;   (S)-3-Chloro-N-(4-(piperidin-3-yl)phenyl)benzamide; and   (RS)-3,4-Dichloro-N-[4-(2-pyrrolidin-2-yl-ethyl)-phenyl]-benzamide.   
     
     
         12 . The compound of  claim 5 , selected from the group consisting of
 (RS)—N-[4-(2-Pyrrolidin-2-yl-ethyl)-phenyl]-4-trifluoromethyl-benzamide;   (RS)-4-Fluoro-N-[4-(2-pyrrolidin-2-yl-ethyl)-phenyl]-benzamide;   (RS)-3-Chloro-N-[4-(2-pyrrolidin-2-yl-ethyl)-phenyl]-benzamide;   (RS)-4-Ethoxy-N-[4-(2-pyrrolidin-2-yl-ethyl)-phenyl]-benzamide;   (RS)-5-Chloro-pyrazine-2-carboxylic acid (4-piperidin-3-yl-phenyl)-amide;   (S)-6-Chloro-N-(4-(piperidin-3-yl)phenyl)nicotinamide;   (R)-5-Chloro-N-(4 (piperidin-3-yl)phenyl)picolinamide;   (S)-5-Chloro-N-(4-(piperidin-3-yl)phenyl)picolinamide;   (RS)-4-Chloro-N-(4-(2-(piperidin-2-yl)ethyl)phenyl)benzamide; and   (RS)-5-Ethoxy-N-(4-(2-(pyrrolidin-2-yl)ethyl)phenyl)picolinamide.   
     
     
         13 . The compound of  claim 5 , selected from the group consisting of
 (R)—N-(4 (2-(Piperidin-2-yl)ethyl)phenyl)-4-(trifluoromethyl)benzamide;   (RS)-3,4-Dichloro-N-(4-(2-(piperidin-2-yl)ethyl)phenyl)benzamide;   (RS)-4-Ethynyl-(4-(2-(piperidin-2-yl)ethyl)phenyl)benzamide;   (RS)—N-(4-(Piperidin-3-yl)phenyl)-6-(2,2,2-trifluoroethoxy)nicotinamide;   (RS)-5-Ethoxy-pyridine-2-carboxylic acid (4-piperidin-3-yl-phenyl)-amide;   (RS)-4-Methyl-N-(4-(pyrrolidin-3-yl)phenyl)benzamide;   (RS)-4 Methyl-N-(4-(piperidin-3-yl)phenyl)benzamide;   (RS)-4-Methoxy-N-(4-(piperidin-3-yl)phenyl)benzamide;   (RS)—N-(4-(Morpholin-2-yl)phenyl)benzamide; and   (RS)-4-Methyl-N-(4-(morpholin-2-yl)phenyl)benzamide.   
     
     
         14 . The compound of  claim 5 , selected from the group consisting of
 (RS)-4-Methoxy-N-(4-morpholin-2-yl)phenyl)benzamide;   (RS)—N-(4-(Piperidin-3-yl)phenyl)-5-(2,2,2-trifluoroethoxy)picolinamide;   (RS)-4-(benzyloxy)-N-(4-(morpholin-2-yl)phenyl)benzamide;   (RS)-6-chloro-N-(4-(morpholin-2-yl)phenyl)nicotinamide;   (RS)-2-(4-(6-cyanonicotinamido)phenyl)morpholin-4-ium chloride;   (R)-4-Methyl-N-(4-(morpholin-2-yl)phenyl)benzamide;   (S)-4-Methyl-N-(4-(morpholin-2-yl)phenyl)benzamide;   (RS)-4-Ethoxy-N-(4-(morpholin-2-yl)phenyl)benzamide;   (RS)-4-Ethyl-N-(4-(morpholin-2-yl)phenyl)benzamide; and   (R)-4-Chloro-3-methoxy-N-(4-(piperidin-3-yl)phenyl)benzamide.   
     
     
         15 . The compound of  claim 5 , selected from the group consisting of
 (S)-4-Chloro-3-methoxy-N-(4-(piperidin-3-yl)phenyl)benzamide;   (R)-3-Chloro-4-methoxy-N-(4-(piperidin-3-yl)phenyl)benzamide;   (S)-3-Chloro-4-methoxy-N-(4-(piperidin-3-yl)phenyl)benzamide;   (R)—N-(4-(Pyrolidin-3-yl)phenyl)-6 (2,2,2-trifluoroethoxy)nicotinamide;   (S)—N-(4-(Pyrrolidin-3-yl)phenyl)-6-(2,2,2-trifluoroethoxy)nicotinamide;   (RS)-4-(4-Chlorophenoxy)-N-(4-(morpholin-2-yl)phenyl)benzamide;   (R)-6-Chloro-N-(4-(morpholin-2-yl)phenyl)nicotinamide;   (S)-6-Chloro-N-(4-(morpholin-2-yl)phenyl)nicotinamide;   (RS)-3-chloro-N-(4-(morpholin-2-yl)phenyl)benzamide; and   (RS)-5-chloro-N-(4-(morpholin-2-yl)phenyl)nicotinamide.   
     
     
         16 . The compound of  claim 5 , selected from the group consisting of
 (RS)-Methyl 4-((4-(4-(morpholin-2-yl)phenylcarbamoyl)phenoxy)methyl)benzoate;   (RS)-Methyl 2-chloro-4-(4-(4-(morpholin-2-yl)phenylcarbamoyl)phenoxy)benzoate;   (RS)-4-Cyclopropylmethoxy-N-(4-morpholin-2-yl-phenyl)-benzamide;   (RS)-4-(Methylthio)-N-(4-(morpholin-2-yl)phenyl)benzamide;   (RS)-2-Chloro-N-(4-(morpholin-2-yl)phenyl)isonicotinamide;   (RS)-5,6-Dichloro-N-(4-(morpholin-2-yl)phenyl)nicotinamide;   (RS)-4-(2-Chloromethyl-3-hydroxy-2-methyl-propoxy)-N-(4-morpholin-2-yl-phenyl)-benzamide;   (RS)-2,6-Dichloro-N-(4-(morpholin-2-yl)phenyl)isonicotinamide;   (RS)—N-(4-(Morpholin-2-yl)phenyl)-6-(2,2,2-trifluoroethoxy)nicotinamide; and   (R)—N-(4-(Piperidin-3-yl)phenyl)-6-(2,2,2-trifluoroethoxy)nicotinamide.   
     
     
         17 . The compound of  claim 5 , selected from the group consisting of
 (S)—N-(4-(piperidin-3-yl)phenyl-6-(2,2,2-trifluoroethoxy)nicotinamide;   (S)-3-Chloro-4-methyl-N-(4-(piperidin-3-yl)phenyl)benzamide;   (S)-4-Chloro-3-methyl-N-(4-(piperidin-3-yl)phenyl)benzamide;   (S)-3,4-Dimethyl-N-(4-(piperidin-3-yl)phenyl)benzamide;   (R)-4-Chloro-2-fluoro-N-(4-(morpholin-2-yl)phenyl)benzamide;   (S)-4-Chloro-2-fluoro-N-(4-(morpholin-2-yl)phenyl)benzamide;   (RS)—N-(4-(Morpholin-2-yl)phenyl)-2-phenylthiazole-5-carboxamide;   (RS)—N-(4-(Morpholin-2-yl)phenyl)-2-phenylthiazole-4-carboxamide;   (S)—N-(4-(Piperidin-3-yl)phenyl)-3-(trifluoromethyl)benzamide; and   (S)-4-(Methylthio)-N-(4-(piperidin-3-yl)phenyl)benzamide.   
     
     
         18 . The compound of  claim 5 , selected from the group consisting of
 (S)-4-(Ethylthio)-N-(4-(piperidin-3-yl)phenyl)benzamide;   5-Chloro-pyrazine-2-carboxylic acid ((S)-4-piperidin-3-yl-phenyl)-amide;   5-Chloro-pyrazine-2-carboxylic acid ((R)-4-piperidin-3-yl-phenyl)-amide;   (S)—N-(4-(Piperidin-3-yl)phenyl)-6-(trifluoromethyl)nicotinamide;   (S)-6-Methyl-N-(4-(piperidin-3 yl)phenyl)nicotinamide;   (S)-6-(Methylthio)-N-(4-(piperidin-3-yl)phenyl)nicotinamide;   (RS)-6-Ethoxy-N-(4-(morpholin-2-yl)phenyl)nicotinamide;   (RS)—N-(4-(Morpholin-2-yl)phenyl)-2-phenyloxazole-4-carboxamide;   (S)—N-(4-(Piperidin-3-yl)phenyl)-5-(2,2,2-trifluoroethoxy)pyrazin-2-carboxamide; and   (S)-5-Bromo-N-(4-(piperidin-3-yl)phenyl)pyrazine-2-carboxamide 2,2,2-trifluoroacetate.   
     
     
         19 . The compound of  claim 5 , selected from the group consisting of
 (S)-6-Bromo-N-(4-(piperidin-3-yl)phenyl)nicotinamide 2,2,2-trifluoroacetate;   (S)-3-Methyl-N-(4-(piperidin-3-yl)phenyl)benzamide;   (S)-5-(Methylthio)-N-(4-(piperidin-3-yl)phenyl)pyrazine-2-carboxamide;   (S)-3-(Methylthio)-N-(4-(piperidin-3-yl)phenyl)benzamide;   (R)-3,4-Dimethyl-N-(4-(piperidin-3-yl)phenyl)benzamide;   (R)—N-(4-(Piperidin-3-yl)phenyl)-3-(trifluoromethyl)benzamide;   (R)-3-Chloro-N-(4-(morpholin-2-yl)phenyl)benzamide;   (S)-3-Chloro-N-(4-(morpholin-2-yl)phenyl)benzamide;   (R)—N-(Piperidin-3-yl)phenyl)-6-(trifluoromethyl)nicotinamide; and   (R)-4-Methylthio)-N-(4-(morpholin-2-yl)phenyl)benzamide.   
     
     
         20 . The compound of  claim 5 , selected from the group consisting of
 (S)-4-(Methylthio)-N-(4-(morpholin-2-yl)phenyl)benzamide;   (R)—N-(4-(Morpholin-2-yl)phenyl)-6-(2,2,2-trifluoroethoxy)nicotinamide;   (S)—N-(4-(Morpholin-2-yl)phenyl)-6-(2,2,2-trifluoroethoxy)nicotinamide;   (R)-2,6-Dichloro-N-(4-(morpholin-2-yl)phenyl)isonicotinamide;   (S)-2,6-Dichloro-N-(4-(morpholin-2-yl)phenyl)isonicotinamide;   (RS)-2-Chloro-6-methyl-N-(4-(morpholin-2-yl)phenyl)isonicotinamide;   (R)-4-Ethoxy-N-(4-(morpholin-2-yl)phenyl)benzamide;   (S)-4-Ethoxy-N-(4-(morpholin-2-yl)phenyl)benzamide;   (RS)-3-Methyl-N-(4-(morpholin-2-yl)phenyl)benzamide; and   (RS)—N-(4-(Morpholin-2-yl)phenyl)-6-(pyrolidin-1-yl)nicotinamide.   
     
     
         21 . The compound of  claim 5 , selected from the group consisting of
 (RS)—N-(4-(Morpholin-2-yl)phenyl)-2-(trifluoromethyl)isonicotinamide;   (S)-2,6-Dichloro-N-(4-(piperidin-3-yl)phenyl)isonicotinamide;   (S)-2-Chloro-6-methyl-N-(4-(piperidin-3-yl)phenyl)isonicotinamide;   (R)—N-(4-(Morpholin-2-yl)phenyl)-6-(trifluoromethyl)nicotinamide;   (S)—N-(4-(Morpholin-2-yl)phenyl)-6-(trifluoromethyl)nicotinamide;   (R)-2-Chloro-6-methy-N-(4-(morpholin-2-yl)phenyl)isonicotinamide;   (S)-2-Chloro-6-methyl-N-(4-(morpholin-2-yl)phenyl)isonicotinamide;   (RS)—N-(4-(Morpholin-2-yl)phenyl)-2-(pyrazin-2-yl)thiazole-4-carboxamide;   (S)—N-(4-(Piperidin-3-yl)phenyl)-6-propylnicotinamide; and   (S)-6-Ethyl-N-(4-(piperidin-3-yl)phenyl)nicotinamide.   
     
     
         22 . The compound of  claim 5 , selected from the group consisting of
 (RS)—N-(4-(Morpholin-2-yl)phenyl)-1-phenyl-1H-pyrazole-3-carboxamide;   (RS)-2-Ethoxy-N-(4-(morpholin-2-yl)phenyl)isonicotinamide;   (S)-4-Chloro-2-iodo-N-(4-(morpholin-2-yl)phenyl)benzamide;   (S)—N-(4-(1,4-Oxazepan-2-yl)phenyl)-3-chlorobenzamide;   3-Chloro-N-(4-((2S,6S)-6-methylmorpholin-2-yl)phenyl)benzamide;   (R)-4-Chloro-N-(4-(morpholin-2-yl)benzyl)benzamide;   (R)-6-Chloro-N-(4-(morpholin-2-yl)benzyl)nicotinamide;   3-Chlor-N-[4-((2S,5S)-5-methy-morpholin-2-yl)-phenyl]-benzamide; and   3-Chloro-N-[4-((2S,5R)-5-methyl-morpholin-2-yl)-phenyl]-benzamide.   
     
     
         23 . The compound of  claim 1 , wherein X is —(CH 2 ) q —O—. 
     
     
         24 . The compound of  claim 23 , selected from the group consisting of
 (RS)-(4-Pyrrolidin-3-yl-phenyl)-carbamic acid phenyl ester;   (RS)-(4-Pyrrolidin-3-yl-phenyl)-carbamic acid 4-fluoro-phenyl ester;   (RS)-(4-Pyrrolidin-3-yl-phenyl)-carbamic acid 4-chloro-phenyl ester;   (RS)-(4-Pyrrolidin-3-yl-phenyl)-carbamic acid 2-(4-fluoro-phenyl)-ethyl ester;   (RS)-(4-Pyrrolidin-3-yl-phenyl)-carbamic acid 4-fluoro-benzyl ester;   (RS)-(4-Pyrrolidin-3-yl-phenyl)-carbamic acid 2-(4-chloro-phenyl)-ethyl ester;   (RS)-(4-Pyrrolidin-3-yl-phenyl)-carbamic acid 2-(3-chloro-phenyl)-ethyl ester;   (RS)-(4-Pyrrolidin-3-yl-phenyl)-carbamic acid 2-(4-trifluoromethyl-phenyl)-ethyl ester;   (RS)-(4-Pyrrolidin-3-yl-phenyl)-carbamic acid 2-(3-trifluoromethyl-phenyl)-ethyl ester, and   (RS)-(4-Pyrrolidin-3-yl-phenyl)-carbamic acid 2-(2,5-difluoro-phenyl)-ethyl ester.   
     
     
         25 . The compound of  claim 23 , selected from the group consisting of
 (RS)-(4-Pyrrolidin-3-yl-phenyl)-carbamic acid 2-(4-trifluoromethoxy-phenyl)-ethyl ester;   (RS)-(4-Pyrrolidin-3-yl-phenyl)-carbamic acid 2-(3,4-dichloro-phenyl)-ethyl ester;   (RS)-(4-Pyrrolidin-3-yl-phenyl)-carbamic acid (RS)-1-(4-chloro-phenyl)-ethyl ester,   (RS)-(4-Pyrrolidin-3-yl-phenyl)-carbamic acid 3-(4-chloro-phenyl)-propyl ester;   (RS)-(4-Pyrrolidin-3-yl-phenyl)-carbamic acid indan-2-yl ester;   (RS)-(4-Pyrrolidin-3-yl-phenyl)-carbamic acid (RS)-1-(4-chloro-phenyl)-2,2,2-trifluoro-ethyl ester and   (S)-2,3-Dihydro-1H-inden-2-yl 4-(piperidin-3-yl)phenylcarbamate 2,2,2-trifluoroacetate.   
     
     
         26 . The compound of  claim 1 , wherein X is —O(CHR″) q —. 
     
     
         27 . The compound of  claim 26 , selected form the group consisting of
 (S)-2-(4-Chlorophenoxy)-N-(4-(piperidin-3-yl)phenyl)acetamide   (S)-4-chlorobenzyl 4-(piperidin-3-yl)phenylcarbamate.   
     
     
         28 . The compound of  claim 1 , wherein X is —CHR″—. 
     
     
         29 . The compound of  claim 28 , selected from the group consisting of
 (RS)-2-(4-Chloro-phenyl)-N-(4-pyrrolidin-3-yl-phenyl)-acetamide;   (RS)—N—((RS)-4-Pyrrolidin-3-yl-phenyl)-2-(3-trifluoromethyl-phenyl)-propionamide; and   (RS)—N-(4-Pyrrolidin-3-yl-phenyl)-2-(3-trifluoromethoxy-phenyl)-propionamide.   
     
     
         30 . The compound of  claim 1 , wherein X is —CH 2 CH 2 —. 
     
     
         31 . The compound of  claim 30 , selected from the group consisting of
 (RS)-3-(2-Chloro-phenyl)-N-(4-pyrrolidin-3-yl-phenyl)-propionamide and   (RS)-3-(4-Chloro-phenyl)-N-(4-piperidin-3-yl-phenyl)-propionamide.   
     
     
         32 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula I 
       
         
           
           
               
               
           
         
         wherein 
         R is hydrogen or lower alkyl; 
         R 1  is —(CH 2 ) n —(O) o -heterocycloalkyl or —C(O)-heterocycloalkyl, wherein the heterocycloalkyl group is optionally substituted by lower alkyl, hydroxy, halogen or by —(CH 2 ) p -aryl; 
         n is 0, 1 or 2; 
         o is 0 or 1; 
         p is 0, 1 or 2; 
         R 2  is CF 3 , cycloalkyl, optionally substituted by lower alkoxy or halogen, or is indan-2-yl, or is heterocycloalkyl, optionally substituted by heteroaryl,
 or is aryl or heteroaryl, wherein the aromatic rings of the aryl or heteroaryl are optionally substituted by one or two substituents, selected from lower alkyl, halogen, heteroaryl, hydroxy, CF 3 , OCF 3 , OCH 2 CF 3 , OCH 2 -cycloalkyl, OCH 2 C(CH 2 OH)(CH 2 Cl)(CH 3 ), S-lower alkyl, lower alkoxy, CH 2 -lower alkoxy, lower alkynyl or cyano, or by —C(O)-phenyl, —O-phenyl, —O—CH 2 -phenyl, phenyl or —CH 2 -phenyl, and wherein the phenyl rings are optionally substituted by halogen, —C(O)-lower alkyl, —C(O)OH or —C(O)O-lower alkyl, or the aromatic rings are optionally substituted by heterocycloalkyl, OCH 2 -oxetan-3-yl or O-tetrahydropyran-4-yl, optionally substituted by lower alkyl; 
 
         X is a bond, —NR′—, —CH 2 NH—, —CHR″—, —(CHR″) q —O—, —O—(CHR″) q — or —(CH 2 ) 2 —; 
         Y is a bond or —CH 2 — 
         R′ is hydrogen or lower alkyl, 
         R″ is hydrogen, lower alkyl, CF 3 , lower alkoxy, 
         q is 0, 1, 2 or 3; 
         or a pharmaceutically suitable acid addition salt thereof 
         and a pharmaceutically acceptable carrier.