Substituted amides

1. A compound of structural fomula I:

or a pharmaceutically acceptable salt thereof, wherein;

R 1 is selected from:

(1) aryl, and

(2) aryl-C 1-4 alkyl,

wherein each alkyl is optionally substituted with one to four substituents independently selected from R a , and each aryl is optionally substituted with one to four substituents independently selected from R b ;

R 2 is selected from:

(1) aryl,

(2) aryl-C 1-4 alkyl,

wherein each alkyl is optionally substituted with one to four substituents independently selected from R a , and each aryl is optionally substituted with one to four substituents independently selected from R b ;

R 3 is selected from:

(1) hydrogen, and

(2) C 1-4 alkyl,

wherein each alkyl is optionally substituted with one to four substituents independently selected from R a ;

R 4 is selected from:

(1) hydrogen, and

(2) C 1-4 alkyl,

wherein each alkyl is optionally substituted with one to four substituents independently selected from R a ;

R 5 is selected from pyridyloxy and C 1-8 alkyl substituted with pyridyloxy, wherein alkyl is optionally substituted with one to four substituents independently selected from R a , and pyridyl is unsubstituted or substituted with one to three substituents selected from R h ,

each R a is independently selected from:

(1) —OR d ,

(2) —NR c S(O) m R d ,

(3) halogen,

(4) —SR d ,

(5) —S(O) m NR c R d ,

(6) —NR c R d ,

(7) —C(O)R d ,

(8) —CO 2 R d ,

(9) —CN,

(10) —C(O)NR c R d ,

(11) —NR c C(O)R d ,

(12) —NR c C(O)OR d ,

(13) —NR c C(O)NR c R d ,

(14) —CF 3 , and

(15) —OCF 3 ;

each R b is independently selected from:

(1) R a ,

(2) C 1-10 alkyl,

(3) oxo,

(4) aryl, and

(5) arylC 1-4 alkyl;

R c and R d are independently selected from:

(1) hydrogen,

(2) C 1-10 alkyl,

(3) C 2-10 alkenyl,

(4) cycloalkyl,

(5) cycloalkyl-C 1-10 alkyl,

(6) aryl, and

(7) aryl-C 1-10 alkyl,

each R c and R d may be unsubstituted or substituted with one to three substituents selected from R h ;

each R h is independently selected from:

(1) halogen,

(2) C 1-10 alkyl,

(3) —OC 1-4 alkyl,

(4) —SC 1-4 alkyl,

(5) —CN,

(6) —CF 3 , and

(7) —OCF 3 ,

m is selected from 1 and 2.

2. The compound according to claim 1 , wherein R 4 is selected from:

(1) hydrogen, and

(2) methyl;

and pharmaceutically acceptable salts thereof.

3. The compound according to claim 2 , wherein R 3 is selected from hydrogen, methyl and ethyl;

and pharmaceutically acceptable salts thereof.

4. The compound according to claim 3 , wherein R 1 is aryl, wherein aryl is phenyl,

wherein each aryl is optionally substituted with one to three substitutents independently selected from R b ;

and pharmaceutically acceptable salts thereof.

5. The compound according to claim 3 , wherein R 2 is selected from: aryl-C 1-4 alkyl, wherein aryl is phenyl, and wherein each alkyl is optionally substituted with one R a substiruent, and each aryl is optionally substituted with one to three substituents independently selected from R b ;

and pharmaceutically acceptable salts thereof.

6. The compound according to claim 3 , selected from:

(1)N-[2,3-bis(4-chlorophenyl)-1-methylpropyl]-2-(3-pyridyloxy)-2-methylpropanamide;

(2)N-[2,3-bis(4-chlorophenyl)-1-methylpropyl]-2-(2-pyridyloxy)-2-methylpropanamide;

(3)N-[2,3-bis(4-chlorophenyl)-1-methylpropyl]-2-(2-pyridyloxy)-2-methylpropanamide;

(4)N-[2,3-bis(4-chlorophenyl)-1-methylpropyl]-2-(4-pyridyloxy)-2-methylpropanamide;

(5)N-[3-(4-chlorophenyl)-2-(3-fluorophenyl)-1-methylpropyl]-2-(2-pyridyloxy)-2-methylpropanamide;

(6)N-[3-(4-chlorophenyl)-1-methyl-2-phenylpropyl]-2-(3-pyridyloxy)-2-methylpropanamide;

(7)N-[3-(4-chlorophenyl)-1-methyl-2-phenylpropyl]-2-(2-pyridyloxy)-2-methylpropanamide;

(8)N-[3-(4-chlorophenyl)-1-methyl-2-phenylpropyl]-2-(2-pyridyloxy)-2-methylpropanamide;

(9)N-[3-(4-chlorophenyl)-1-methyl-2-phenylpropyl]-2-(4-pyridyloxy)-2-methylpropanamide;

(10)N-[2,3-bis(4-chlorophenyl)-1-methylpropyl]-2-(6-methyl-3-pyridyloxy)-2-methylpropanamide;

(11)N-[3-(4-chlorophenyl)-2-phenyl-1-methylpropyl]-2-(6-methyl-3-pyridyloxy)-2-methylpropanamide;

(12)N-[3-(4-chlorophenyl)-2-(3,5-difluorophenyl)-1-methylpropyl]-2-methyl-2(2-pyridyloxy)propanamide;

(13)N-[3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-methyl-2(2-pyridyloxy)propanamide;

(14)N-[2-(3-chlorophenyl)-3-(4-chlorophenyl)-1-methylpropyl]-2-methyl-2(2-pyridyloxy)propanamide;

(15)N-[3-(4-chlorophenyl)-2-(3,5-difluorophenyl)-1-methylpropyl]-2-methyl-2(2-pyridyloxy)propanamide;

(16)N-[2-(3-bromophenyl)-3-(4-chlorophenyl)-1-methylpropyl]-2-methyl-2(2-pyridyloxy)propanamide;

(17)N-[3-(4-chlorophenyl)-2-(3-iodophenyl)-1-methylpropyl]-2-methyl-2(2-pyridyloxy)propanamide;

(18)N-[3-(4-chlorophenyl)-2(S)-phenyl-1(S)-methylpropyl]-2-(6-chloro-2-pyridyloxy)-2-methylpropanamide;

(19)N-[3-(4-chlorophenyl)-2(S)-phenyl-1(S)-methylpropyl]-2-(4-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide;

(20)N-[3-(4-chlorophenyl)-2(S)-phenyl-1(S)-methylpropyl]-2(R)-(4-trifluoromethyl-2-pyridyloxy)propanamide;

(21)N-[3-(4-chlorophenyl)-2-(3-fluorophenyl)-1-methylpropyl]-2-(5-chloro-2-pyridyloxy)-2-methylpropanamide;

(22)N-[3-(4-chlorophenyl)-2-(3-fluorophenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide;

(23)N-[3-(4-chlorophenyl)-2-(3-fluorophenyl)-1-methylpropyl]-2-(4-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide;

(24)N-[2-(3-bromo-5-fluorophenyl)-3-(4-fluorophenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide;

(25)N-[2-(3-chlorophenyl)-3-(4-chlorophenyl)-1-methylpropyl]-2-(5-chloro-2-pyridyloxy)-2-methylpropanamide;

(26)N-[2-(3-chlorophenyl)-3-(4-chlorophenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide;

(27)N-[2-(3-bromophenyl)-3-(4-chlorophenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide;

(28)N-[3-(4-chlorophenyl)-2-(3-trifluoromethylphenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide;

(29)N-[3-(4-chlorophenyl)-2-(3-methylphenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide;

(30)N-[3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-(5-chloro-2-pyridyloxy)-2-methylpropanamide;

(31)N-[3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide;

(32)N-[2-(3-bromophenyl)-3-(4-chlorophenyl)-1-methylpropyl]-2-(5-chloro-2-pyridyloxy)-2-methylpropanamide;

(33)N-[3-(4-chlorophenyl)-2-(3-cyano-5-fluorophenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide;

(34)N-[2-(3-cyano-5-fluorophenyl)-3-(4-fluorophenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide;

(35)N-[3-(4-chloro-3-iodophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide;

(36) 2-methyl-N-[1-methyl-3(4-methylphenyl)-2-phenylpropyl]-2-{[5-(trifluoromethyl)pyridin-2-yl]oxy}propanamide;

(37)N-[3-(4-methoxyphenyl)-1-methyl-2-phenylpropyl]-2-methyl-2-{[5-(trifluoromethyl)pyridin-2-yl]oxy}propanamide;

(38)N-[3-(4-fluorophenyl)-1-methyl-2-phenylpropyl]-2-methyl-2-{[5-(trifluoromethyl)pyridin-2-yl]oxy}propanamide;

(39)N-[3-(4-cyanophenyl)-1-methyl-2-phenylpropyl]-2-methyl-2-{[5-(trifluoromethyl)pyridin-2-yl]oxy}propanamide;

(40)N-[2-(3-cyanophenyl)-3-(4-fluorophenyl)-1-methylpropyl]-2-methyl-2-{[5-(trifluoromethyl)pyridin-2-yl]oxy}propanamide;

and pharmaceutically acceptable salts thereof.

7. The compound according to claim 3 , selected from:

(1) N-[2,3-bis(4-chlorophenyl)-1-methylpropyl]-2-(3-pyridyloxy)-2-methylpropanamide;

(2) N-[2,3-bis(4-chlorophenyl)-1-methylpropyl]-2-(2-pyridyloxy)-2-methylbutanamide;

(3) N-[2,3-bis(4-chlorophenyl)-1-methylpropyl]-2-(4-pyridyloxy)-2-methylpropanamide;

(4) N-[3-(4-chlorophenyl)-2-(3-fluorophenyl)-1-methylpropyl]-2-(2-pyridyloxy)-2-methylpropanamide;

(5) N-[3-(4-chlorophenyl)-1-methyl-2-phenylpropyl]-2-(2-pyridyloxy)-2-methylbutanamide;

(6) N-[3-(4-chlorophenyl)-1-methyl-2-phenylpropyl]-2-(2-pyridyloxy)-2-methylpropanamide;

(7) N-[3-(4-chlorophenyl)-1-methyl-2-phenylpropyl]-2-(4-pyridyloxy)-2-methylpropanamide;

(8) N-[2,3-bis(4-chlorophenyl)-1-methylpropyl]-2-(6-methyl-3-pyridyloxy)-2-methylpropanamide;

(9) N-[3-(4-chlorophenyl)-2-phenyl-1-methylpropyl]-2-(6-methyl-3-pyridyloxy)-2-methylpropanamide;

(10) N-[3-(4-chlorophenyl)-2-(3,5-difluorophenyl)-1-methylpropyl]-2-methyl-2-(2-pyridyloxy)propanamide;

(11) N-[3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-methyl-2-(2-pyridyloxy)propanamide;

(12) N-[2-(3-chlorophenyl)-3-(4-chlorophenyl)-1-methylpropyl]-2-methyl-2-(2-pyridyloxy)propanamide;

(13) N-[2-(3-chlorophenyl)-3-(4-chlorophenyl)-1-methylpropyl]-2-methyl-2-(2-pyridyloxy)propanamide;

(14) N-[3-(4-chlorophenyl)-2-(3-iodophenyl)-1-methylpropyl]-2-methyl-2-(2-pyridyloxy)propanamide;

and pharmaceutically acceptable salts thereof.

8. The compound according to claim 1 , wherein:

R 1 is phenyl,

wherein each phenyl is optionally substituted with one or two substituents selected from halogen, methyl, trifluoromethyl, cyano and methoxy;

R 2 is selected from:

(1) benzyl,

(2) phenylethyl,

(3) 3-phenylpropyl,

(4) 2-phenylpropyl,

wherein each phenyl moiety is optionally substituted with one or two R b substituents selected from halogen, trifluoromethyl, cyano, methoxycarbonyl, and methoxy;

R 3 is selected from:

(1) hydrogen,

(2) methyl, and

(3) ethyl;

R 4 is hydrogen;

R 5 is C 1-8 alkyl substituted with pyridyloxy, wherein each pyridyl is unsubstituted or substituted with one to three substituents selected from R h ;

each R h is independently selected from:

(1) halogen,

(2) C 1-4 alkyl,

(3) —O—C 1-4 alkyl,

(4) —S—C 1-4 alkyl,

(5) —CN,

(6) —CF 3 , and

(7) —OCF 3 ;

and pharmaceutically acceptable salts thereof.

9. The compound according to claim 8 , selected from:

(1) N-[2,3-bis(4-chlorophenyl)-1-methylpropyl]-2-(3-pyridyloxy)-2-methylpropanamide;

(2) N-[2,3-bis(4-chlorophenyl)-1-methylpropyl]-2-(2-pyridyloxy)-2-methylbutanamide;

(3) N-[2,3-bis(4-chlorophenyl)-1-methylpropyl]-2-(2-pyridyloxy)-2-methylpropanamide;

(4) N-[2,3-bis(4-chlorophenyl)-1-methylpropyl]-2-(4-pyridyloxy)-2-methylpropanamide;

(5) N-[3-(4-chlorophenyl)-2-(3-fluorophenyl)-1-methylpropyl]-2-(2-pyridyloxy)-2-methylpropanamide;

(6) N-[3-(4-chlorophenyl)-1-methyl-2-phenylpropyl]-2-(3-pyridyloxy)-2-methylpropanamide;

(7) N-[3-(4-chlorophenyl)-1-methyl-2-phenylpropyl]-2-(2-pyridyloxy)-2-methylbutanamide;

(8) N-[3-(4-chlorophenyl)-1-methyl-2-phenylpropyl]-2-(2-pyridyloxy)-2-methylpropanamide;

(9) N-[3-(4-chlorophenyl)-1-methyl-2-phenylpropyl]-2-(4-pyridyloxy)-2-methylpropanamide;

(10) N-[2,3-bis(4-chlorophenyl)-1-methylpropyl]-2-(6-methyl-3-pyridyloxy)-2-methylpropanamide;

(11) N-[3-(4-chlorophenyl)-2-phenyl-1-methylpropyl]-2-(6-methyl-3-pyridyloxy)-2-methylpropanamide;

(12) N-[3-(4-chlorophenyl)-2-(3,5-difluorophenyl)-1-methylpropyl]-2-methyl-2-(2-pyridyloxy)propanamide;

(13) N-[2-(3-chlorophenyl)-3-(4-chlorophenyl)-1-methylpropyl]-2-methyl-2-(2-pyndyloxy)propanamide;

(14) N-[2-(3-bromophenyl)-3-(4-chlorophenyl)-1-methylpropyl]-2-methyl-2-(2-pyrldyloxy)propanamide;

(15) N-[3-(4-chlorophenyl)-2-(3-iodophenyl)-1-methylpropyl]-2-methyl-2-(2-pyridyloxy)propanamide;

(16) N-[3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-methyl-2-(2-pyridyloxy)propanamide;

and pharmaceutically acceptable salts thereof.

10. The compound according to claim 3 , wherein:

R 1 ls aryl, wherein oxyl is phenyl;

wherein aryl is optionally substituted with one to three substituents independently selected from R b ;

R 2 is aryl-C 1-4 alkyl, wherein aryl is phenyl,

wherein aryl is optionally substituted with one to three substituents independently selected from R b ;

R 3 is methyl;

R 4 is hydrogen;

R 5 is

wherein pyridyl is unsubstituted or substituted with one to three substituents selected from R h ;

each R b is independently selected from:

(1) halogen,

(2) cyano,

(3) trifluoromethyl,

(4) trifluoromethoxy,

(5) C 1-3 alkyloxy, and

(6) C 1-3 alkyl;

each R h is independently selected from:

(1) halogen,

(2) C 1-3 alkyl,

(3) —CN, and

(4) —CF 3 ;

wherein when pyridyl groups are otherwise unsubstituted on the nitrogen, they may optionally be present as the N-oxide;

and pharmaceutically acceptable salts thereof.

11. The compound according to claim 10 , wherein:

R 1 is phenyl, wherein each phenyl is optionally substituted with one or two substituients independently selected from R b ;

R 2 is phenylmethyl, wherein each phenyl is optionally substituted with one to three substituents independently selected from R b ;

each R b is independently selected from:

(1) halogen,

(2) cyano,

(3) C 1-3 alkyloxy, and

(4) C 1-3 aIkyl;

each R h is independently selected from:

(1) fluoro,

(2) chloro,

(3) methyl,

(4) —CN, and

(5) —CF 3 ;

and pharmaceutically acceptable salts thereof.

12. The compound according to claim 11 , selected from:

(1) N-[3-(4-chlorophenyl)-1-methyl-2-phenylpropyl]-2-(2-pyridyloxy)-2-methylpropanamide

(2) N-[3-(4-chlorophenyl)-2-(3,5-difluorophenyl)-1-methylpropyl]-2-(2-pyridyloxy)-2-methylpropanamide;

(3) N-[3-(4-chlorophenyl)-1-methyl-2-phenyl-propyl]-2-(5-chloro-2-pyridyloxy)-2-methylpropanamide;

(4) N-[3-(4-chlorophenyl)-1-methyl-2-phenylpropyl]-2-(6-methyl-pyridyloxy)-2-methylpropanamide;

(5) N-[3-(4-chlorophenyl)-1-methyl-2-phenylpropyl]-2-(5-trifluoromethylpyridyloxy)-2-methylpropanamide;

(6) N-[3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide;

(7) N-[3-(4-chlorophenyl)-2-(3-methylphenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide;

(8) N-[3-(4-chlorophenyl)-2-phenyl-1-methylpropyl]-2-(4-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide;

(9) N-[3-(4-fluoro-phenyl)-2-(3-cyano-phenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide;

(10) N-[3-(4-chloro-phenyl)-2-(N-methyl-anilino)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide;

(11) N-[3-(4-methoxy-phenyl)-2-(3-cyano-phenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide;

and pharmaceutically acceptable salts thereof.

13. The compound according to claim 11 , wherein R 5 is:

and pharmaceutically acceptable salts thereof.

14. The compound according to claim 13 selected from:

(1) N-[(3-(4chlorophenyl)-1-methyl-2-phenylpropyl]-2-(5-trifluoromethylpyridyloxy)-2-methylpropanamide;

(2) N[3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide;

(3) N-[3-(4-chlorophenyl)-2-(3-methylphenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide;

(4) N-[3-(4-fluoro-phenyl)-2-(3-cyano-phenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide;

(5) N-[3-(4-chloro-phenyl)-2-(N-methyl-anilino)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide;

(6) N-3-(4-methoxy-phenyl)-2-(3-cyano-phenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide;

and pharmaceutically acceptable salts thereof.

15. N-[3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide, or a pharmaceutically acceptable salt thereof.

16. A method of treating an eating disorder associated with excessive food intake selected from obesity, bulimia nervosa, and compulsive eating disorders comprising administration to a patient in need of such treatment of a therapeutically effective amount of a compound according to claim 1 .

17. The method according to claim 16 wherein the eating disorder associated with excessive food intake is obesity.

18. A composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.

19. A method of treating obesity comprising administration to a patient in need of such treatment of a therapeutically effective amount of the compound according to claim 15 .

20. A composition comprising the compound according to claim 15 and a pharmaceutically acceptable carrier.