Substituted pyrimidines

1. A compound of structural formula I:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is selected from:

(1) —OC 1-6 alkyl, unsubstituted or substituted with one to three R c substituents,

(2) cycloalkyloxy-, unsubstituted or substituted with one to three R c substituents,

(3) cycloalkyl-C 1-4 alkyloxy-, unsubstituted or substituted with one to three R c substituents,

(4) cycloheteroalkyloxy-, unsubstituted or substituted with one to three R c substituents,

(5) cycloheteroalkyl-C 1-4 alkyloxy, unsubstituted or substituted with one to three R c substituents,

(6) phenyloxy, unsubstituted or substituted with one to three R c substituents,

(7) heteroaryloxy, unsubstituted or substituted with one to three R c substituents,

(8) phenyl-C 1-4 alkyloxy, unsubstituted or substituted with one to three R c substituents,

(9) heteroaryl-C 1-4 alkyloxy, unsubstituted or substituted with one to three R c substituents,

(10) —NR a R b ,

(11) —NR b C(O)R a ,

(12) —CO 2 H,

(13) C 1-6 alkyloxycarbonyl-, unsubstituted or substituted with one to three R c substituents,

(14) cycloalkyloxycarbonyl-, unsubstituted or substituted with one to three R c substituents,

(15) cycloalkyl-C 1-4 alkyloxycarbonyl-, unsubstituted or substituted with one to three R c substituents,

(16) phenyloxycarbonyl, unsubstituted or substituted with one to three R c substituents,

(17) heteroaryloxycarbonyl, unsubstituted or substituted with one to three R c substituents,

(18) phenyl-C 1-4 alkyloxycarbonyl, unsubstituted or substituted with one to three R c substituents,

(19) heteroaryl-C 1-4 alkyloxycarbonyl, unsubstituted or substituted with one to three R c substituents,

(20) —C(O)NR a R b ,

(21) cyano,

(22) —SO 2 C 1-6 alkyl, unsubstituted or substituted with one to three R c substituents;

provided that R 1 is not NH 2 ;

R 2 is selected from:

(1) hydrogen,

(2) C 1-10 alkyl,

(3) —OR a ,

(4) —NR a R b ,

(5) —NR a C(O)R b ,

(6) —CO 2 R a ,

(7) —C(O)NR a R b ,

(8) cyano,

(9) —SR a , and

(10) —SO 2 R a ;

wherein R 3 and R 4 are each independently selected from:

each R a is independently selected from:

(1) hydrogen,

(2) C 1-10 alkyl,

(3) C 2-10 alkenyl,

(4) cycloalkyl,

(5) cycloalkyl-C 1-10 alkyl;

(6) cycloheteroalkyl,

(7) cycloheteroalkyl-C 1-10 alkyl;

(8) aryl,

(9) heteroaryl,

(10) aryl-C 1-10 alkyl, and

(11) heteroaryl-C 1-10 alkyl; and

each R b is independently selected from:

(1) hydrogen,

(2) C 1-10 alkyl,

(3) C 2-10 alkenyl,

(4) cycloalkyl,

(5) cycloalkyl-C 1-10 alkyl;

(6) cycloheteroalkyl,

(7) cycloheteroalkyl-C 1-10 alkyl;

(8) aryl,

(9) heteroaryl,

(10) aryl-C 1-10 alkyl, and

(11) heteroaryl-C 1-10 alkyl, or

R a and R b together with the nitrogen atom to which they are attached form a bridged or unbridged heterocyclic ring of 4 to 7 members containing 0-2 additional heteroatoms independently selected from oxygen, sulfur and N—R d ,

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

each R c is independently selected from:

(1) C 1-10 alkyl,

(2) —OR d ,

(3) —NR e S(O) m R d ,

(4) halogen,

(5) —SR d ,

(6) —S(O) m NR d R e ,

(7) —NR d R e ,

(8) —C(O)R d ,

(9) —CN,

(10) —C(O)NR d R e ,

(11) —NR e C(O)R d ,

(12) —NR e C(O)ORd e ,

(13) —NR e C(O)NR d R e ,

(14) —CF 3 ,

(15) —OCF 3 ,

(16) cycloheteroalkyl,

(17) aryl,

(18) arylC 1-4 alkyl,

(19) heteroaryl, and

(20) heteroarylC 1-4 alkyl;

R d and R e 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) cycloheteroalkyl,

(7) cycloheteroalkyl-C 1-10 alkyl;

(8) aryl,

(9) heteroaryl,

(10) aryl-C 1-10 alkyl, and

(11) heteroaryl-C 1-10 alkyl, or

R d and R e together with the nitrogen atom to which they are attached form a bridged or unbridged heterocyclic ring of 4 to 7 members containing 0-2 additional heteroatoms independently selected from oxygen, sulfur and N—R f ,

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

R f is independently selected from:

(1) halogen,

(2) C 1-10 alkyl,

(3) —O—C 1-4 alkyl,

(4) —S—C 1-4 alkyl,

(5) —CN,

(6) —CF 3 , and

(7) —OCF 3 ;

each R g is independently selected from:

(1) halogen,

(2) C 1-10 alkyl,

(3) —O—C 1-4 alkyl,

(4) —S—C 1-4 alkyl,

(5) —CN,

(6) —CF 3 , and

(7) —OCF 3 ; and

m is selected from 1 and 2.

2. The compound according to claim 1 , wherein:

R a and R b are each selected from:

(1) hydrogen,

(2) C 1-6 alkyl, unsubstituted or substituted with one to three R c substituents,

(3) cycloalkyl, unsubstituted or substituted with one to three R c substituents,

(4) cycloalkyl-C 1-4 alkyl, unsubstituted or substituted with one to three R c substituents,

(5) phenyl, unsubstituted or substituted with one to three R c substituents,

(6) heteroaryl, unsubstituted or substituted with one to three R c substituents,

(7) phenyl-C 1-4 alkyl, unsubstituted or substituted with one to three R c substituents, or

(8) heteroaryl-C 1-4 alkyl, unsubstituted or substituted with one to three R c substituents, or

when bonded to nitrogen, R a and R b together with the nitrogen atom to which they are attached form a bridged or unbridged heterocyclic ring of 4 to 7 members containing 0-2 additional heteroatoms independently selected from oxygen, sulfur and N—R d , unsubstituted or substituted on carbon with one to three R c substituents;

or a pharmaceutically acceptable salt thereof.

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

(1) —OC 1-6 alkyl, unsubstituted or substituted with one to three R c substituents,

(2) C 4-7 cycloalkyloxy-, unsubstituted or substituted with one to two R c substituents,

(3) cycloalkyl-C 1-3 alkyloxy-, unsubstituted or substituted with one to two R c substituents,

(4) phenyloxy, unsubstituted or substituted with one to two R c substituents,

(5) pyridyloxy, unsubstituted or substituted with one to two R c substituents,

(6) phenyl-C 1-3 alkyloxy, unsubstituted or substituted with one to two R c substituents,

(7) pyridyl-C 1-3 alkyloxy, unsubstituted or substituted with one to two R c substituents,

(8) —NR a R b , wherein:

R a is selected from:

(a) C 1-6 alkyl, unsubstituted or substituted with one to three R c substituents,

(b) cycloalkyl, unsubstituted or substituted with one to two R c substituents,

(c) cycloalkyl-C 1-4 alkyl, unsubstituted or substituted with one to two R c substituents,

(d) phenyl, unsubstituted or substituted with one to two R c substituents,

(e) heteroaryl, unsubstituted or substituted with one to two R c substituents,

(f) benzyl, unsubstituted or substituted with one to two R c substituents,

R b is selected from:

(a) hydrogen,

(b) C 1-6 alkyl, unsubstituted or substituted with one to three R c substituents, or

R a and R b together with the nitrogen atom to which they are attached form a bridged or unbridged heterocyclic ring of 4 to 7 members containing 0-2 additional heteroatoms independently selected from oxygen, sulfur and N—R d , unsubstituted or substituted on carbon with one to two R c substituents,

(9) —NR b C(O)R a , wherein:

R a is selected from:

(a) hydrogen,

(b) C 1-6 alkyl, unsubstituted or substituted with one to three R c substituents,

(c) cycloalkyl, unsubstituted or substituted with one to two R c substituents,

(d) cycloalkyl-C 1-4 alkyl, unsubstituted or substituted with one to two R c substituents,

(e) phenyl, unsubstituted or substituted with one to two R c substituents,

(f) pyridyl, unsubstituted or substituted with one to three R c substituents,

(g) benzyl, unsubstituted or substituted with one to two R c substituents,

(h) pyridylmethyl-, unsubstituted or substituted with one to three R c substituents,

R b is selected from:

(a) hydrogen,

(b) C 1-6 alkyl, unsubstituted or substituted with one to three R c substituents,

(11) —CO 2 H,

(12) C 1-6 alkyloxycarbonyl-, unsubstituted or substituted with one to three R c substituents,

(13) —C(O)NR a R b , wherein:

R a is selected from:

(a) hydrogen,

(b) C 1-6 alkyl, unsubstituted or substituted with one to three R c substituents,

R b is selected from:

(a) hydrogen, and

(b) C 1-6 alkyl, unsubstituted or substituted with one to three R c substituents,

(14) cyano

(15) —SC 1-6 alkyl, unsubstituted or substituted with one to three R c substituents, and

(16) —SO 2 C 1-6 alkyl, unsubstituted or substituted with one to three R c substituents;

each R c is independently selected from:

(1) C 1-3 alkyl,

(2) hydroxy,

(3) —OC 1-3 alkyl,

(4) halogen,

(5) —SCH 3 ,

(6) —SH,

(7) —NR d R e ,

(8) —C(O)C 1-3 alkyl,

(9) —CN,

(10) —CF 3 ,

(11) —OCF 3 ,

(12) cycloheteroalkyl,

(13) phenyl,

(14) benzyl, and

(15) pyridyl;

or a pharmaceutically acceptable salt thereof.

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

(1) hydrogen,

(2) C 1-6 alkyl,

(3) —OH,

(4) —OC 1-6 alkyl, unsubstituted or substituted with one to three R c substituents,

(5) cycloalkyloxy-, unsubstituted or substituted with one to three R c substituents,

(6) cycloalkyl-C 1-4 alkyloxy-, unsubstituted or substituted with one to three R c substituents,

(7) cycloheteroalkyloxy-, unsubstituted or substituted with one to three R c substituents,

(8) cycloheteroalkyl-C 1-4 alkyloxy, unsubstituted or substituted with one to three R c substituents,

(9) phenyloxy, unsubstituted or substituted with one to three R c substituents,

(10) heteroaryloxy, unsubstituted or substituted with one to three R c substituents,

(11) phenyl-C 1-4 alkyloxy, unsubstituted or substituted with one to three R c substituents,

(12) heteroaryl-C 1-4 alkyloxy, unsubstituted or substituted with one to three R c substituents,

(13) —NR a R b ,

(14) —NR b C(O)R a ,

(15) —CO 2 H,

(16) C 1-6 alkyloxycarbonyl-, unsubstituted or substituted with one to three R c substituents,

(17) cycloalkyloxycarbonyl-, unsubstituted or substituted with one to three R c substituents,

(18) cycloalkyl-C 1-4 alkyloxycarbonyl-, unsubstituted or substituted with one to three R c substituents,

(19) phenyloxycarbonyl, unsubstituted or substituted with one to three R c substituents,

(20) heteroaryloxycarbonyl, unsubstituted or substituted with one to three R c substituents,

(21) phenyl-C 1-4 alkyloxycarbonyl, unsubstituted or substituted with one to three R c substituents,

(22) heteroaryl-C 1-4 alkyloxycarbonyl, unsubstituted or substituted with one to three R c substituents,

(23) —C(O)NR a R b ,

(24) cyano,

(25) —SC 1-6 alkyl, unsubstituted or substituted with one to three R c substituents, and

(26) —SO 2 C 1-6 alkyl, unsubstituted or substituted with one to three R c substituents,

or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 1 , wherein:

R 2 is selected from:

(1) hydrogen,

(2) C 1-6 alkyl,

(3) —OH,

(4) —OC 1-6 alkyl, unsubstituted or substituted with one to three R c substituents,

(5) C 4-7 cycloalkyloxy-, unsubstituted or substituted with one to two R c substituents,

(6) C 4-7 cycloalkyl-C 1-3 alkyloxy-, unsubstituted or substituted with one to two R c substituents,

(7) phenyloxy, unsubstituted or substituted with one to two R c substituents,

(8) pyridyloxy, unsubstituted or substituted with one to two R c substituents,

(9) phenyl-C 1-3 alkyloxy, unsubstituted or substituted with one to two R c substituents,

(10) pyridyl-C 1-3 alkyloxy, unsubstituted or substituted with one to two R c substituents,

(11) —NR a R b , wherein:

R a is selected from:

(a) hydrogen,

(b) C 1-6 alkyl, unsubstituted or substituted with one to three R c substituents,

(c) cycloalkyl, unsubstituted or substituted with one to two R c substituents,

(d) cycloalkyl-C 1-4 alkyl, unsubstituted or substituted with one to two R c substituents,

(e) phenyl, unsubstituted or substituted with one to two R c substituents,

(f) heteroaryl, unsubstituted or substituted with one to two R c substituents,

(g) benzyl, unsubstituted or substituted with one to two R c substituents,

R b is selected from:

(a) hydrogen,

(b) C 1-6 alkyl, unsubstituted or substituted with one to three R c substituents, or

R a and R b together with the nitrogen atom to which they are attached form a bridged or unbridged heterocyclic ring of 4 to 7 members, unsubstituted or substituted on carbon with one to two R c substitutents,

(12) —NHC(O)R a , wherein:

R a is selected from:

(a) hydrogen,

(b) C 1-6 alkyl, unsubstituted or substituted with one to three R c substituents,

(c) cycloalkyl, unsubstituted or substituted with one to two R c substituents,

(d) cycloalkyl-C 1-4 alkyl, unsubstituted or substituted with one to two R c substituents,

(e) phenyl, unsubstituted or substituted with one to two R c substituents,

(f) pyridyl, unsubstituted or substituted with one to three R c substituents,

(g) benzyl, unsubstituted or substituted with one to two R c substituents,

(h) pyridylmethyl-, unsubstituted or substituted with one to three R c substituents,

(13) cyano, and

(14) —SO 2 C 1-6 alkyl, unsubstituted or substituted with one to three R c substituents;

or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 1 , wherein:

R 1 is selected from:

(1) methoxy, ethyloxy, isopropyloxy, n-butyloxy, sec-butyloxy, isobutyloxy, tert.-butyloxy, n-pentyloxy, or 2,2-dimethylpropyloxy, unsubstituted or substituted with one to three halo, hydroxy, or methoxy substituents,

(2) cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, or cycloheptyloxy,

(3) cyclopropylmethoxy, cyclobutylmethoxy, cyclopentylmethoxy, cyclohexylmethoxy, or cycloheptylmethoxy,

(4) 4-fluorophenyloxy, 4-chlorophenyloxy, 4-methoxyphenyloxy, 3-fluorophenyloxy, 3-chlorophenyloxy, 3,4-difluorophenyloxy, 3,4-dichlorophenyloxy, 3,5-difluorophenyloxy, 3,5-dichlorophenyloxy or phenyloxy,

(5) 4-pyridyloxy, 3-pyridyloxy, 2-pyridyloxy, 6-chloro-3-pyridyloxy, or 5-chloro-3-pyridyloxy,

(6) benzyloxy, 3-fluorobenzyloxy, 3-chlorobenzyloxy, 4-fluorobenzyloxy, 4-chlorobenzyloxy, 3,4-difluorobenzyloxy, 3,4-dichlorobenzyloxy, 3,5-difluorobenzyloxy, 3,5-dichlorobenzyloxy, 2,4-fluorobenzyloxy, 2,4-dichlorobenzyloxy, alpha-methyl-4-fluorobenzyloxy, alpha-methyl-4-chlorobenzyloxy, alpha,alpha-dimethyl-4-fluorobenzyloxy, or alpha,alpha-dimethyl-4-chlorobenzyloxy,

(7) 2-pyridylmethyloxy 3,-pyridylmethyloxy, or 4-pyridylmethyloxy,

(8) N-methylamino, N,N-dimethyamino, N,N-diisopropylamino, or —N(CH 3 )CH 2 CH 2 N(CH 3 ) 2 , or N-containing heterocycloalkyl bonded via nitrogen selected from: morpholinyl, thiomorpholinyl, pyrrolidnyl, piperidinyl, and [2.2.1]azabicycloheptyl,

(9) —NHCOR a wherein R a is selected from:

(a) hydrogen,

(b) C 1-4 alkyl,

(c) C 4-6 cycloalkyl, and

(d) phenyl, 4-fluorophenyl, 4-chlorophenyl, 3,4-difluorophenyl, or 3,4-dichlorophenyl,

(10) —CO 2 H,

(11) —C(O)NH 2 ,

(12) —CN, and

(13) —SO 2 CH 3 ;

R 2 is selected from:

(1) hydrogen,

(2) methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, n-pentyl, or 2,2-dimethylpropyloxy,

(3) —OH,

(4) methoxy, ethyloxy, isopropyloxy, n-butyloxy, sec-butyloxy, isobutyloxy, tert.-butyloxy, n-pentyloxy, or 2,2-dimethylpropyloxy, unsubstituted or substituted with one to three halo, hydroxy, or methoxy substituents,

(5) cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, or cycloheptyloxy,

(6) cyclopropylmethoxy, cyclobutylmethoxy, cyclopentylmethoxy, cyclohexylmethoxy, or cycloheptylmethoxy,

(7) 4-fluorophenyloxy, 4-chlorophenyloxy, 3-fluorophenyloxy, 3-chlorophenyloxy, 3-cyanophenyloxy, 3,4-difluorophenyloxy, 3,4-dichlorophenyloxy, 3,5-difluorophenyloxy, 3,5-dichlorophenyloxy, or phenyloxy,

(8) benzyloxy, 3-fluorobenzyloxy, 3-chlorobenzyloxy, 4-fluorobenzyloxy, 4-chlorobenzyloxy, 3,4-difluorobenzyloxy, 3,4-dichlorobenzyloxy, 3,5-difluorobenzyloxy, 3,5-dichlorobenzyloxy, 2,4-fluorobenzyloxy, or 2,4-dichlorobenzyloxy,

(9) 4-pyridyloxy, 3-pyridyloxy, 2-pyridyloxy, 6-chloro-3-pyridyloxy, or 5-chloro-3-pyridyloxy,

(10) amino, N-methylamino, N-ethylamino, N,N-dimethyamino, N,N-diethylamino, N,N-diisopropylamino, or N-containing heterocycloalkyl bonded via nitrogen selected from: pyrrolidinyl, and piperidinyl,

(11) —NHCOR a wherein R a is selected from:

(a) hydrogen, and

(b) C 1-4 alkyl,

(12) —CN, and

(14) —SO 2 CH 3 ;

R 3 and R 4 are each independently selected from:

(1) 4-chlorophenyl,

(2) 4-methoxyphenyl,

(3) 4-fluorophenyl,

(4) 4-trifluoromethylphenyl,

(5) 3-chlorophenyl,

(6) 3-methoxyphenyl,

(7) 2,4-dichlorophenyl, and

(8) 2-chloro-4-methylthiophenyl;

or a pharmaceutically acceptable salt thereof.

7. The compound according to claim 6 , wherein:

R 3 is 4-chlorophenyl and R 4 is 2,4-dichlorophenyl, or a pharmaceutically acceptable salt thereof.

8. A method of treating a disease mediated by the Cannabinoid-1 receptor selected from: substance abuse disorders and eating disorders associated with excessive food intake, comprising administration to a patient in need of such treatment of a therapeutically effective amount of a compound of structural formula I:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is selected from:

(1) C 1-10 alkyl,

(2) —OR a ,

(3) —NR a R b ,

(4) —NR b C(O)R a ,

(5) —CO 2 R a ,

(6) —C(O)NR a R b ,

(7) cyano, and

(8) —SO 2 R b ,

provided that R 1 is not —NH 2 ;

R 2 is selected from:

(1) hydrogen,

(2) C 1-10 alkyl,

(3) —OR a ,

(4) —NR a R b ,

(5) —NR a C(O)R b ,

(6) —CO 2 R a ,

(7) —C(O)NR a R b ,

(8) cyano,

(9) —SR a , and

(10) —SO 2 R a ;

wherein R 3 and R 4 are each independently selected from:

each R a is independently selected from:

(1) hydrogen,

(2) C 1-10 alkyl,

(3) C 2-10 alkenyl,

(4) cycloalkyl,

(5) cycloalkyl-C 1-10 alkyl;

(6) cycloheteroalkyl,

(7) cycloheteroalkyl-C 1-10 alkyl;

(8) aryl,

(9) heteroaryl,

(10) aryl-C 1-10 alkyl, and

(11) heteroaryl-C 1-10 alkyl; and

each R b is independently selected from:

(1) hydrogen,

(2) C 1-10 alkyl,

(3) C 2-10 alkenyl,

(4) cycloalkyl,

(5) cycloalkyl-C 1-10 alkyl;

(6) cycloheteroalkyl,

(7) cycloheteroalkyl-C 1-10 alkyl;

(8) aryl,

(9) heteroaryl,

(10) aryl-C 1-10 alkyl, and

(11) heteroaryl-C 1-10 alkyl, or

R a and R b together with the nitrogen atom to which they are attached form a bridged or unbridged heterocyclic ring of 4 to 7 members containing 0-2 additional heteroatoms independently selected from oxygen, sulfur and N—R d ,

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

each R c is independently selected from:

(1) C 1-10 alkyl,

(2) —OR d ,

(3) —NR e S(O) m R d ,

(4) halogen,

(5) —SR d ,

(6) —S(O) m NR d R e ,

(7) —NR d R e ,

(8) —C(O)R d ,

(9) —CO 2 R d ,

(10) —CN,

(11) —C(O)NR d R e ,

(12) —NR e C(O)R d ,

(13) —NR e C(O)ORd e ,

(14) —NR e C(O)NR d R e ,

(15) —CF 3 ,

(16) —OCF 3 ,

(17) cycloheteroalkyl,

(18) aryl,

(19) arylC 1-4 alkyl,

(20) heteroaryl, and

(21) heteroarylC 1-4 alkyl;

R d and R e 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) cycloheteroalkyl,

(7) cycloheteroalkyl-C 1-10 alkyl;

(8) aryl,

(9) heteroaryl,

(10) aryl-C 1-10 alkyl, and

(11) heteroaryl-C 1-10 alkyl, or

R d and R e together with the nitrogen atom to which they are attached form a bridged or unbridged heterocyclic ring of 4 to 7 members containing 0-2 additional heteroatoms independently selected from oxygen, sulfur and N—R f ,

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

R f is independently selected from:

(1) halogen,

(2) C 1-10 alkyl,

(3) —O—C 1-4 alkyl,

(4) —S—C 1-4 alkyl,

(5) —CN,

(6) —CF 3 , and

(7) —OCF 3 ;

each R g is independently selected from:

(1) halogen,

(2) C 1-10 alkyl,

(3) —O—C 1-4 alkyl,

(4) —S—C 1-4 alkyl,

(5) —CN,

(6) —CF 3 , and

(7) —OCF 3 ; and

m is selected from 1 and 2.

9. The method according to claim 8 wherein the disease mediated by the Cannabinoid-1 receptor is an eating disorder associated with excessive food intake.

10. The method according to claim 9 wherein the eating disorder associated with excessive food intake is selected from obesity, bulimia nervosa, and compulsive eating disorders.

11. The method according to claim 10 wherein the eating disorder associated with excessive food intake is obesity.

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

13. The method according to claim 8 for treating substance abuse disorders, wherein the abused substance is nicotine in a person dependent on nicotine.

14. The compound according to claim 1 , selected from:

(1) 2-(4-fluorobenzyloxy)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)pyrimidine;

(2) 2-(4-fluorobenzyloxy)-4-(2-chloro-4-methylthiophenyl)-5-(4-chlorophenyl)-pyrimidine;

(3) 2-(3,4-difluorobenzyloxy)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)pyrimidine;

(4) 2-(3,4-difluorobenzyloxy)-4-(2-chloro-4-methylthio-phenyl)-5-(4-chlorophenyl)-pyrimidine;

(5) 2-(4-chlorobenzyloxy)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)pyrimidine;

(6) 2-(4-chlorobenzyloxy)-4-(2-chloro-4-methylthio-phenyl)-5-(4-chlorophenyl)-pyrimidine;

(7) 2-(3,4-dichlorobenzyloxy)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)pyrimidine;

(8) 2-(3,4-dichlorobenzyloxy)-4-(2-chloro-4-methylthio-phenyl)-5-(4-chlorophenyl)-pyrimidine;

(9) 2-(3-fluorobenzyloxy)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)pyrimidine;

(10) 2-(3-fluorobenzyloxy)-4-(2-chloro-4-methylthio-phenyl)-5-(4-chlorophenyl)-pyrimidine;

(11) 2-(3-chlorobenzylamino)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-pyrimidine;

(12) 2-(N,N-dimethylamino)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)pyrimidine;

(13) 2-carboxy-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)pyrimidine;

(14) 2-methoxy-4-hydroxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(15) 2-(3,4-difluorobenzyloxy)-4-hydroxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(16) 2-(3,4-difluorobenzyloxy)-4-hydroxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(17) 2,4-bis-(3,4-difluorobenyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(18) 2,4-dimethoxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(19) 2,4-diethoxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(20) 2,4-diisopropoxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(21) 2-methylsulfonyl-4-(3,4-difluorophenoxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(22) 2,4-bis(3,4-difluorophenoxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(23) 2-cyano-4-(3,4-difluorophenoxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(24) 2-(3,4-difluorobenzyloxy)-4-cyano-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(25) 2-cyano-4-(3,4-difluorobenzyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(26) 2,4-bis(cyano)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(27) 2-(3,4-difluorophenoxy)-4-methyl-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(28) 2-ethyl-4-(3,4-difluorophenoxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(29) 2-isopropy-4-(3,4-difluorophenoxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(30) 2-(3,4-difluorobenzyloxy)-4-methyl-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(31) 2-(3,4-difluorobenzyloxy)-4-ethyl-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(32) 2-(3,4-difluorobenzyloxy)-4-(N-methylamino)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(33) 2-(3,4-difluorophenoxy)-4-amino-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(34) 2-(3,4-difluorobenzyloxy)-4-(amino)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(35) 2-(3,4-difluorophenoxy)-4-(acetylamino)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(36) 2-(3,4-difluorobenzyloxy)-4-(acetylamino)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(37) 2-(3,4-difluorophenoxy)-4-(N-pyrrolidinyl)-5-[4-chlorophenyl]-6-[2,4-dichlorophenyl]pyrimidine;

(38) 2-(cyclopropylmethoxy)-4-(N-pyrrolidinyl)-5-[4-chlorophenyl]-6-[2,4-dichlorophenyl]pyrimidine;

(39) 2-(N,N-diethylamino)-4-(3,4-difluorobenzyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(40) 2-(N,N-diisopropylamino)-4-(3,4-difluorobenzyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(41) 2-(N-pyrrolidinyl)-4-(3,4-difluorobenzyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(42) 2-(N-piperidyl)-4-(3,4-difluorobenzyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(43) 2-(N-morpholinyl)-4-(3,4-difluorobenzyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(44) 2-(7-N-[2.2.1]-azabicycloheptyl)-4-(3,4-difluorophenoxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(45) 2-(n-propionyl)-4-(3,4-difluorophenoxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(46) 2-(N-(2-methyl)propionyl)-4-(3,4-difluorophenoxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(47) 2-(N-(3-methyl)butyryl)-4-(3,4-difluorophenoxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(48) 2-(aminocarbonyl)-4-(3,4-difluorophenoxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(49) 2-(carboxy)-4-(3,4-difluorophenoxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(50) 2-(2-hydroxyethyleneoxy)-4-(3,4-difluorophenoxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(51) 2-(2-methoxyethyleneoxy)-4-(3,4-difluorophenoxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(52) 2-(cyclohexylmethyloxy)-4-isopropoxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(53) 2-cyclohexyloxy-4-isopropoxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(54) 2-(3,4-difluorophenoxy)-4-cyclohexyloxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(55) 2-(3,4-difluorobenzyloxy)-4-cyclohexyloxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(56) 2,4-bis(cyclopropylmethyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(57) 2-cyclopropyloxy-4-(3-pyridyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(58) 2-(N-pyrrolidinyl)-4-cyclopropyloxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(59) 2,4-bis(isopropyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(60) 2-(3,4-difluorobenzyloxy)-4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)pyrimidine;

(61) 2-(4-chlorobenzyloxy)-4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)pyrimidine;

(62) 2-(3-fluorobenzyloxy)-4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)pyrimidine;

(63) 2-(3-chlorobenzyloxy)-4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)pyrimidine;

(64) 2-(4-fluorobenzyloxy)-4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)pyrimidine;

(65) 2-(α-methyl-4-fluorobenzyloxy-)-4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)pyrimidine;

(66) 2-(α-methyl-4-fluorobenzyloxy)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)pyrimidine;

(67) 2-(3-pyridylmethoxy)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)pyrimidine;

(68) 2-(n-butyloxy)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)pyrimidine;

(69) 2-(2,4-dichlorobenzyloxy)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)pyrimidine;

(70) 2-(cyclohexylmethoxy)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)pyrimidine;

(71) 2-(3,5-dichlorobenzyloxy)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)pyrimidine;

(72) 2-(6-chloro-3-pyridylmethoxy)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)pyrimidine;

(73) 2-(α,α-dimethyl-4-fluorobenzyloxy)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)pyrimidine;

(74) 2-(4-fluorophenyloxy)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)pyrimidine;

(75) 2-(3-fluorophenyloxy)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)pyrimidine;

(76) 2-(3,4-difluorophenyloxy)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)pyrimidine;

(77) 2-(3-chlorophenyloxy)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)pyrimidine;

(78) 2-(4-methoxyphenyloxy)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)pyrimidine;

(79) 2-(3-pyridyloxy)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)pyrimidine;

(80) 2-(5-chloro-3-pyridyloxy)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)pyrimidine;

(81) 2-(N-(4-fluorobenzamido))-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)pyrimidine;

(82) 2-(N-(cyclohexylcarboxamido))-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)pyrimidine;

(83) 2,4-bis(cyclobutylmethoxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(84) 2-cyclobutylmethoxy-4-(6-fluoro-3-pyridyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(85) 2-cyclobutylmethoxy-4-(5-chloro-3-pyridyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(86) 2-methylsulfonyl-4-(3-pyridyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(87) 2-cyclobutylmethoxy-4-(3-pyridyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(88) 2-(2,2-dimethylpropyloxy)-4-(3-pyridyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(89) 2-(2-t-butyloxy)-4-(3-pyridyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(90) 2-(2-cyclobutyloxy)-4-(3-pyridyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(91) 2-(n-propyloxy)-4-(3-pyridyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(92) 2-(n-butyloxy)-4-(3-pyridyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(93) 2-(sec-butyloxy)-4-(3-pyridyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(94) 2-(iso-butyloxy)-4-(3-pyridyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(95) 2-(isopropyloxy)-4-(3-pyridyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(96) 2-(n-pentyloxy)-4-(3-pyridyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(97) 2-cyclopropyloxy-4-(4-pyridyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(98) 2,4-bis-(4-pyridyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(99) 2-(isobutyloxy)-4-(3,4-difluorophenoxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(100) 2-(cyclopropylmethoxy)-4-(3,4-difluorophenoxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(101) 2-(isopropyloxy)-4-(3,4-difluorophenoxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(102) 2-ethoxy-4-(3,4-difluorophenoxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(103) 2-(N-pyrrolidinyl)-4-(3,4-difluorophenoxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(104) 2-(N,N′,N′-trimethyl-ethylenediamino)-4-(3,4-difluorophenoxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(105) 2-(N-piperidinyl)-4-(3,4-difluorophenoxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(106) 2-(N-morpholinyl)-ethylenediamino-4-(3,4-difluorophenoxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(107) 2-dimethylamino-4-(3,4-difluorophenoxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(108) 2-(N-pyrrolidinyl)-4-(3-pyridyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(109) 2-methylsulfonyl-4-(2-pyridyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(110) 2-(2-isopropyloxy)-4-(2-pyridyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(111) 2-(2-N,N′,N′-trimethyl-ethylenediamino)-4-(2-pyridyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(112) 2-(2-pyrrolindinyl)-4-(2-pyridyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(113) 2-(methylsulfonyl)-4-methoxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(114) 2-methoxy-4-(methylsulfonyl)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(115) 2-(3,4-difluorophenyloxy)-4-methoxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(116) 2-methoxy-4-(3,4-difluorophenyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(117) 2-(3-fluorophenyloxy)-4-methoxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(118) 2-methoxy-4-(3-fluorophenyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(119) 2-methoxy-4-(2-pyridyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(120) 2-(2-pyridyloxy)-4-methoxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(121) 2-(5-chloro-3-pyridyloxy)-4-methoxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(122) 2-methoxy-4-(5-chloro-3-pyridyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(123) 2-(3-pyridyloxy)-4-methoxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(124) 2-methoxy-4-(3-pyridyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(125) 2-methoxy-4-(4-fluorophenyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(126) 2-methoxy-4-(3,5-difluorophenyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(127) 2-methoxy-4-(3-cyanophenyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(128) 2-(3,4-difluorobenzyloxy)-4-methoxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(129) 2-methoxy-4-(3,4-difluorobenzyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(130) 2-(methylsulfonyl)-4-ethoxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(131) 2-ethoxy-4-(methylsulfonyl)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(132) 2-(3,4-difluorobenzyloxy)-4-ethoxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(133) 2-ethoxy-4-(3,4-difluorophenyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(134) 2-(methylsulfonyl)-4-isopropyloxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(135) 2-isopropyloxy-4-(methylsulfonyl)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(136) 2-(3,4-difluorobenzyloxy)-4-isopropyloxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(137) 2-isopropyloxy-4-(3,4-difluorophenyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(138) 2-(3,4-difluorobenzyloxy)-4-pyrrolidinyl-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(139) 2-(3,4-difluorobenzyloxy)-4-diethylamino-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(140) 2-(3,4-difluorobenzyloxy)-4-dimethylamino-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine;

(141) 2-(3,4-difluorophenoxy)-4-methoxy-5-(4-fluorophenyl)-6-[2,4-dichlorophenyl]pyrimidine;

(142) 2-(3,4-difluorophenoxy)-4-methoxy-5-(4-methoxyphenyl)-6-[2,4-dichlorophenyl]pyrimidine;

(143) 2-(3,4-difluorophenoxy)-4-methoxy-5-(4-trifluoromethylphenyl)-6-[2,4-dichlorophenyl]pyrimidine;

(144) 2-(3,4-difluorophenoxy)-4-methoxy-5-(3-chlorophenyl)-6-[2,4-dichlorophenyl]pyrimidine; and

(145) 2-(3,4-difluorophenoxy)-4-methoxy-5-(3-methoxyphenyl)-6-[2,4-dichlorophenyl]pyrimidine,

or a pharmaceutically acceptable salt thereof.