1,2,3-triazole derivatives for use as stearoyl-CoA desaturase inhibitors

1. A compound of formula (I):

wherein:

X represents —CONH—, —NHCO— or —CH 2 NH—;

R 1 represents a —C 6-10 aryl optionally substituted by one, two or three groups independently selected from:

(a) —C 1-6 alkyl, —OCH 3 , —C 1-6 haloalkyl, —OC 1-6 haloalkyl, —C 3-6 cycloalkyl, —OC 3-6 cycloalkyl or halogen;

(b) phenyl optionally substituted by one, two or three groups independently selected from: halogen;

R 2 represents —C 1-6 alkyl;

R 3 represents a —C 6-10 aryl optionally substituted by one, two or three groups independently selected from:

(a) —C 1-6 alkyl, —C 1-6 alkenyl, —C 1-6 alkoxy, —O(CH 2 ) m R 4 , —(CH 2 ) m OC(═O)R 4 , —(CH 2 ) n CO 2 R 5 , —(CH 2 ) n OC(═O)R 5 , —C 0-6 alkylOH, —C(═O)NHR 6 , —(CH 2 ) p NHC(═O)R 7 , —O(CH 2 ) q NR 8 R 9 , —OC 1-6 alkylOH, —C 1-6 haloalkyl, —OC 1-6 haloalkyl, —C 3-6 cycloalkyl, —OC 3-6 cycloalkyl or halogen;

(b) oxazole;

R 4 represents —C 6-10 aryl;

R 5 represents —H or —C 1-6 alkyl;

R 6 represents —H or —C 1-3 alkyl or —C 1-3 alkylOH;

R 7 represents —H or —C 1-3 alkyl;

R 8 represents —H or —C 1-3 alkyl;

R 9 represents —H or —C 1-3 alkyl;

m represents 1-3;

n represents 0-3;

p represents 0-3; and

q represents 1-3;

or a pharmaceutically acceptable salt thereof.

2. A compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 1 wherein X represents —CONH— or —CH 2 NH—.

3. A compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 1 wherein R 1 represents phenyl optionally substituted by one, two or three groups independently selected from:

(a) —C 1-6 alkyl, —OCH 3 , —C 1-6 haloalkyl, —OC 1-6 haloalkyl, —C 3-6 cycloalkyl, —OC 3-6 cycloalkyl, or halogen;

(b) phenyl optionally substituted by one, two or three groups independently selected from halogen.

4. A compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 1 wherein R 2 represents —C 1-3 alkyl.

5. A compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 1 wherein R 3 represents phenyl optionally substituted by one, two or three groups independently selected from:

(a) —C 1-6 alkyl, —C 1-6 alkenyl, —C 1-6 alkoxy, —O(CH 2 ) m R 4 , —(CH 2 ) m OC(═O)R 4 , —(CH 2 ) n CO 2 R 5 , —(CH 2 ) n OC(═O)R 5 , —C 0-6 alkylOH, —C(═O)NHR 6 , —(CH 2 ) p NHC(═O)R 7 , —O(CH 2 ) q NR 8 R 9 , —OC 1-6 alkylOH, —C 1-6 haloalkyl, —OC 1-6 haloalkyl, —C 3-6 cycloalkyl, —OC 3-6 cycloalkyl or halogen;

(b) oxazole.

6. A compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 1 wherein R 3 represents phenyl optionally substituted by:

(i) one group independently selected from —(CH 2 ) n CO 2 R 5 or —C(═O)NHR 6 and/or,

(ii) one, two or three groups independently selected from:

(a) —C 1-6 alkyl, —C 1-6 alkenyl, —C 1-6 alkoxy, —O(CH 2 ) m R 4 , —(CH 2 ) m OC(═O)R 4 , —(CH 2 ) n C(═O)R 5 , —C 0-6 alkylOH, —(CH 2 ) p NHC(═O)R 7 , —O(CH 2 ) q NR 8 R 9 , —OC 1-6 alkylOH, —C 1-6 haloalkyl, —OC 1-6 haloalkyl, —C 3-6 cycloalkyl, —OC 3-6 cycloalkyl or halogen;

(b) oxazole.

7. A compound of formula (I) according to claim 1 selected from:

N-[3,4-bis(methyloxy)phenyl]-1-[(4-fluorophenyl)methyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

N-[3,4-bis(methyloxy)phenyl]-1-[(4-bromophenyl)methyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(4-Bromophenyl)methyl]-5-methyl-N-{4-[(phenylmethyl)oxy]phenyl}-1H-1,2,3-triazole-4-carboxamide,

1-[(4-Fluorophenyl)methyl]-5-methyl-N-{4-[(phenylmethyl)oxy]phenyl}-1H-1,2,3-triazole-4-carboxamide,

1-[(4-Fluorophenyl)methyl]-5-methyl-N-{4-[(3-methylbutyl)oxy]phenyl}-1H-1,2,3-triazole-4-carboxamide,

1-[(4-Bromophenyl)methyl]-5-methyl-N-{4-[(3-methylbutyl)oxy]phenyl}-1H-1,2,3-triazole-4-carboxamide,

5-Methyl-1-(phenylmethyl)-N-{4-[(phenylmethyl)oxy]phenyl}-1H-1,2,3-triazole-4-carboxamide,

5-Methyl-N-{4-[(3-methylbutyl)oxy]phenyl}-1-(phenylmethyl)-1H-1,2,3-triazole-4-carboxamide,

1-[(2′-Chloro-4-biphenylyl)methyl]-5-methyl-N-{4-[(3-methylbutyl)oxy]phenyl}-1H-1,2,3-triazole-4-carboxamide,

5-Methyl-N-{4-[(3-methylbutyl)oxy]phenyl}-1-[(4-methylphenyl)methyl]-1H-1,2,3-triazole-4-carboxamide,

5-Methyl-N-{4-[(3-methylbutyl)oxy]phenyl}-1-{[4-(1-methylethyl)phenyl]methyl}-1H-1,2,3-triazole-4-carboxamide,

N-[3,4-Bis(methyloxy)phenyl]-5-methyl-1-[(4-methylphenyl)methyl]-1H-1,2,3-triazole-4-carboxamide,

1-(2-Biphenylylmethyl)-N-[3,4-bis(methyloxy)phenyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-5-methyl-N-[4-(1,3-oxazol-2-yl)phenyl]-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-[4-(hydroxymethyl)phenyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

Methyl 4-[({1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]-3-(methyloxy)benzoate,

1-[(3,4-Dichlorophenyl)methyl]-5-methyl-N-{3-[(methylamino)carbonyl]phenyl}-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-5-methyl-N-{4-[(methylamino)carbonyl]phenyl}-1H-1,2,3-triazole-4-carboxamide,

Ethyl 3-[({1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]benzoate,

N-[3-(acetylamino)phenyl]-1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

N-[4-(acetylamino)phenyl]-1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-[3-(hydroxymethyl)-2-methylphenyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-[3-(hydroxymethyl)phenyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

Methyl 3-[({[4(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]-4-(methyloxy)benzoate,

1-[(3,4-Dichlorophenyl)methyl]-N-[4-hydroxy-3-(hydroxymethyl)phenyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

Ethyl {4-[({1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]phenyl}acetate,

Methyl 4-[({1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]-2-(methyloxy)benzoate,

Methyl 5-[({1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]-2-hydroxybenzoate,

Methyl {3-[({1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]phenyl}acetate,

1-[(3,4-Dichlorophenyl)methyl]-N-(3-hydroxyphenyl)-5-methyl-1H-1,2,3-triazole-4-carboxamide,

Methyl 5-[({1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]-2-fluorobenzoate,

N-[5-(Aminocarbonyl)-2-(methyloxy)phenyl]-1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

Methyl 4-chloro-3-[({1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]benzoate,

Methyl [3-[({1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]-4-(methyloxy)phenyl]acetate,

Methyl 3-[({1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]-4-fluorobenzoate,

N-[3-(hydroxymethyl)phenyl]-5-methyl-1-(phenylmethyl)-1H-1,2,3-triazole-4-carboxamide,

N-[4-(hydroxymethyl)phenyl]-5-methyl-1-(phenylmethyl)-1H-1,2,3-triazole-4-carboxamide,

N-[3-(hydroxymethyl)-2-methylphenyl]-5-methyl-1-(phenylmethyl)-1H-1,2,3-triazole-4-carboxamide,

1-[(3,5-Dichlorophenyl)methyl]-N-[3-(hydroxymethyl)phenyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

Methyl 3-[({1-[(3,5-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]-4-(methyloxy)benzoate,

1-[(3,5-Dichlorophenyl)methyl]-N-[3-(hydroxymethyl)-2-methylphenyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

N-{3-[(Acetylamino)methyl]phenyl}-1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-[3-(1-hydroxyethyl)phenyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

N-[4-chloro-3-(hydroxymethyl)phenyl]-1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

Dimethyl 4-[({1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]-1,2-benzenedicarboxylate,

Methyl 5-[({1-[(3,5-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]-2-fluorobenzoate,

Ethyl 4-[({1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]benzoate,

1-[(3,4-Dichlorophenyl)methyl]-N-[4-(hydroxymethyl)-2-(methyloxy)phenyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-[4-(2-hydroxyethyl)phenyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-[5-(hydroxymethyl)-2-(methyloxy)phenyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

N-[3,5-Bis(hydroxymethyl)phenyl]-1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-[4-fluoro-3-(hydroxymethyl)phenyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-[5-(2-hydroxyethyl)-2-(methyloxy)phenyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-[2-fluoro-5-(hydroxymethyl)phenyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

N-[2-chloro-5-(hydroxymethyl)phenyl]-1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,5-Dichlorophenyl)methyl]-N-[5-(hydroxymethyl)-2-(methyloxy)phenyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

N-[3,4-Bis(hydroxymethyl)phenyl]-1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,5-Dichlorophenyl)methyl]-N-[4-fluoro-3-(hydroxymethyl)phenyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

N-[3,5-bis(hydroxymethyl)phenyl]-5-methyl-1-(phenylmethyl)-1H-1,2,3-triazole-4-carboxamide,

N-[3,5-bis(hydroxymethyl)phenyl]-1-[(3-chlorophenyl)methyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-[3-(2-hydroxyethyl)phenyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

3-[({1-[(3,4-Dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]benzoic acid,

3-[({1-[(3,4-Dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]-4-(methyloxy)benzoic acid,

5-({[5-Methyl-1-(phenylmethyl)-1H-1,2,3-triazol-4-yl]carbonyl}amino)-1,3-benzenedicarboxylic acid,

4-[({1-[(3,4-Dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]benzoic acid,

1-[(3,4-Dichlorophenyl)methyl]-N-{3-[(ethylamino)carbonyl]phenyl}-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-(3-{[(2-hydroxyethyl)amino]carbonyl}phenyl)-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-5-methyl-N-[5-[(methylamino)carbonyl]-2-(methyloxy)phenyl]-1H-1,2,3-triazole-4-carboxamide,

{3-[({1-[(3,4-Dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]phenyl}methyl acetate,

{3-[({1-[(3,5-Dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]phenyl}methyl acetate,

{3-[({1-[(3,4-Dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]phenyl}methyl benzoate,

{3-[({1-[(3,5-Dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]phenyl}methyl benzoate,

1-[(3,4-Dichlorophenyl)methyl]-N-{4-[(2-hydroxyethyl)oxy]phenyl}-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-5-methyl-N-[4-(1-methylethenyl)-2-(methyloxy)phenyl]-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-[3-(1-hydroxy-1-methylethyl)phenyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-[4-{[2-(dimethylamino)ethyl]oxy}-3-(hydroxymethyl)phenyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-{3-[(2-hydroxyethyl)oxy]phenyl}-5-methyl-1H-1,2,3-triazole-4-carboxamide, and

{5-[({1-[(3,4-Dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}methyl)amino]benzene-1,3-diyl}dimethanol,

or a pharmaceutically acceptable salt thereof.

8. A compound of formula (I) according to claim 1 selected from:

N-[3,4-bis(hydroxymethyl)phenyl]-5-methyl-1-(phenylmethyl)-1H-1,2,3-triazole-4-carboxamide,

N-[3,5-bis(hydroxymethyl)phenyl]-1-[(4-fluorophenyl)methyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

N-[3,4-bis(hydroxymethyl)phenyl]-1-[(3-chlorophenyl)methyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

N-[3,4-bis(hydroxymethyl)phenyl]-1-[(4-fluorophenyl)methyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

N-[3,5-bis(hydroxymethyl)phenyl]-1-[(3-fluorophenyl)methyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

N-[3,4-bis(hydroxymethyl)phenyl]-1-[(3-fluorophenyl)methyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3-chlorophenyl)methyl]-N-[3-(hydroxymethyl)phenyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(4-fluorophenyl)methyl]-N-[3-(hydroxymethyl)phenyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3-chlorophenyl)methyl]-N-[4-(hydroxymethyl)phenyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3-fluorophenyl)methyl]-N-[3-(hydroxymethyl)phenyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide

1-[(4-fluorophenyl)methyl]-N-[4-(hydroxymethyl)phenyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3-fluorophenyl)methyl]-N-[4-(hydroxymethyl)phenyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-dichlorophenyl)methyl]-N-{3-(hydroxymethyl)-5-[(methylamino)carbonyl]phenyl}-5-methyl-1H-1,2,3-triazole-4-carboxamide, and

N-{1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}-4-(hydroxymethyl)benzamide;

or a pharmaceutically acceptable salt thereof.

9. A compound of formula (I) according to claim 1 which is N-[3,5-bis(hydroxymethyl)phenyl]-1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide or a pharmaceutically acceptable salt thereof.

10. A pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 1 together with at least one pharmaceutical carrier and/or excipient.

11. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof according to claim 9 and at least one pharmaceutical carrier and/or excipient.

12. A compound of formula (I) according to claim 1 which is 1-[(3,4-Dichlorophenyl)methyl]-N-[4-(hydroxymethyl)phenyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide, or a pharmaceutically acceptable salt thereof.

13. A pharmaceutical composition comprising a compound, or a pharmaceutically acceptable salt thereof according to claim 7 and at least one pharmaceutical carrier and/or excipient.

14. A pharmaceutical composition comprising a compound, or a pharmaceutically acceptable salt thereof according to claim 8 and at least one pharmaceutical carrier and/or excipient.

15. A pharmaceutical composition comprising a compound, or a pharmaceutically acceptable salt thereof according to claim 9 and at least one pharmaceutical carrier and/or excipient adapted for topical administration.

16. A pharmaceutical composition comprising a compound, or a pharmaceutically acceptable salt thereof according to claim 12 and at least one pharmaceutical carrier and/or excipient.