2-oxo-imidazolidine-4-carboxamides as nav1.8 inhibitors

Abstract

Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are inhibitors of Na v 1.8 channel activity and may be useful in the treatment, prevention, management, amelioration, control and suppression of diseases mediated by Na v 1.8 channel activity. The compounds of the present invention may be useful in the treatment, prevention or management of pain disorders, cough disorders, acute itch disorders, and chronic itch disorders.

1 . A composition comprising:
 a) a first compound of structural Formula I:   
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein 
       A is selected from the group consisting of:
 1) phenyl, and 
 2) pyridine, 
 
       wherein each phenyl and pyridine is unsubstituted or substituted with one to five substituents selected from R a ; 
       B is selected from the group consisting of:
 1) phenyl, 
 2) pyridine, 
 3) thiazole, 
 4) pyrimidine, 
 5) pyrazine, 
 6) pyridazine, 
 7) imidazole, 
 8) pyrazole, 
 9) oxazole, 
 10) benzofuran, 
 11) benzo[d]oxazole, 
 12) benzo[d]thiazole, 
 13) indazole, 
 14) thiazolo[5,4-b]pyridine, 
 15) pyrazolo[1,5-a]pyridine, 
 16) —(CH 2 ) 2 -phenyl, 
 17) —CH 2 —O-phenyl, 
 18) —CH 2 —O-pyridine, 
 19) cyclobutane, 
 20) cyclohexane, 
 21) bicyclo[1.1.1]pentane, 
 22) spiro[3.3]heptane, 
 23) azetidine, 
 24) piperidine, 
 25) tetrahydropyran, 
 26) tetrahydrofuran, 
 27) azabicyclo[3.1.0]hexane, 
 28) —CH 2 -cyclohexane, 
 29) —CH 2 -tetrahydropyran, 
 30) CH 2 —O-cyclohexane, and 
 31) bicyclo[4.2.0]octatriene, 
 
       wherein B is unsubstituted or substituted with one to five substituents selected from R b ; 
       R 1  is selected from the group consisting of:
 1) hydrogen, and 
 2) —C 1-6 alkyl, 
 
       wherein alkyl is unsubstituted or substituted with one to five substituents selected from R c ; 
       R 2  is selected from the group consisting of:
 1) hydrogen, and 
 2) —C 1-6 alkyl, 
 
       wherein alkyl is unsubstituted or substituted with one to five substituents selected from R d ; 
       R 3  is selected from the group consisting of:
 1) hydrogen, and 
 2) —C 1-6 alkyl, 
 
       wherein alkyl is unsubstituted or substituted with one to five substituents selected from R f ; 
       R 4  is selected from the group consisting of:
 1) hydrogen, and 
 2) —C 1-6 alkyl, 
 
       wherein alkyl is unsubstituted or substituted with one to five substituents selected from R g ; 
       R 5  is selected from the group consisting of:
 1) hydrogen, and 
 2) —C 1-6 alkyl, 
 
       wherein alkyl is unsubstituted or substituted with one to five halogen substituents; 
       R 6  is hydrogen; 
       R 7  is selected from the group consisting of:
 1) hydrogen, and 
 2) —C 1-6 alkyl, 
 
       wherein alkyl is unsubstituted or substituted with one to five halogen substituents: 
       each R a  is independently selected from the group consisting of:
 1) —CF 3 , 
 2) —OCF 3 , 
 3) —CHF 2 , 
 4) —OCHF 2 , 
 5) —CH 2 CF 3 , 
 6) —OCH 2 CF 3 , 
 7) —CF 2 CH 3 ; 
 8) CN, 
 9) oxo, 
 10) halogen, 
 11) —S(O) 2 C 1-6 alkyl, 
 12) —C 1-6 alkyl, 
 13) —C 2-6 alkenyl, 
 14) —C 2-6 alkynyl, 
 15) —C 3-6 cycloalkyl, 
 16) —C 2-6 cycloheteroalkyl, 
 17) aryl, 
 18) heteroaryl, 
 19) —C 1-6 alkyl-aryl, 
 20) —C 1-6 alkyl-heteroaryl, 
 21) —C 1-6 alkyl-C 3-6 cycloalkyl, 
 22) —C 1-6 alkyl-C 2-6 cycloheteroalkyl, 
 23) —C 2-6 alkenyl-C 3-6 cycloalkyl, 
 24) —C 2-6 alkenyl-C 2-6 cycloheteroalkyl, 
 25) —C 2-6 alkenyl-aryl, 
 26) —C 2-6 alkenyl-heteroaryl, 
 27) —C 2-6 alkynyl-C 3-6 cycloalkyl, 
 28) —C 2-6 alkynyl-C 2-6 cycloheteroalkyl, 
 29) —C 2-6 alkynyl-aryl, 
 30) —C 2-6 alkynyl-heteroaryl, 
 31) —OH, 
 32) —(CH 2 ) p —O—C 1-6 alkyl, 
 33) —(CH 2 ) p —O—C 2-6 alkenyl, 
 34) —(CH 2 ) p —O—C 2-6 alkynyl, 
 35) —(CH 2 ) p —O—C 3-6 cycloalkyl, 
 36) —(CH 2 ) p —O—C 2-6 heterocycloalkyl, 
 37) —(CH 2 ) p —O-aryl, 
 38) —(CH 2 ) p —O-heteroaryl, 
 39) —OC 1-6 alkyl-C 3-6 cycloalkyl, 
 40) —OC 1-6 alkyl-C 2-6 heterocycloalkyl, 
 41) —OC 1-6 alkyl-aryl, 
 42) —OC 1-6 alkyl-heteroaryl, 
 43) —S(O) m R i , 
 44) —C 1-6 alkyl-S(O) m R i , 
 45) —N(R k ) 2 , and 
 46) —NR k R L , 
 
       wherein each R a  is unsubstituted or substituted with one to six substituents selected from halogen, CF 3 , OH, C 1-6 alkyl, and —OC 1-6 alkyl; 
       each R b  is independently selected from the group consisting of:
 1) —CF 3 , 
 2) —OCF 3 , 
 3) —CHF 2 , 
 4) —OCHF 2 , 
 5) —CH 2 CF 3 , 
 6) —OCH 2 CF 3 , 
 7) —CF 2 CH 3 ; 
 8) CN, 
 9) oxo, 
 10) halogen, 
 11) —S(O) 2 C 1-6 alkyl, 
 12) —C 1-6 alkyl, 
 13) —C 2-6 alkenyl, 
 14) —C 2-6 alkynyl, 
 15) —O—C 1-6 alkyl, 
 16) —C 3-6 cycloalkyl, 
 17) —O—C 3-6 cycloalkyl, 
 18) —C 2-6 cycloheteroalkyl, 
 19) aryl, 
 20) heteroaryl, 
 21) —C 1-6 alkyl-aryl, 
 22) —C 1-6 alkyl-heteroaryl, 
 23) —C 1-6 alkyl-C 3-6 cycloalkyl, 
 24) —C 1-6 alkyl-C 2-6 cycloheteroalkyl, 
 25) —C 2-6 alkenyl-C 3-6 cycloalkyl, 
 26) —C 2-6 alkenyl-C 2-6 cycloheteroalkyl, 
 27) —C 2-6 alkenyl-aryl, 
 28) —C 2-6 alkenyl-heteroaryl, 
 29) —C 2-6 alkynyl-C 3-6 cycloalkyl, 
 30) —C 2-6 alkynyl-C 2-6 cycloheteroalkyl, 
 31) —C 2-6 alkynyl-aryl, 
 32) —C 2-6 alkynyl-heteroaryl, 
 33) —OH, 
 34) —(CH 2 ) q —OC 1-6 alkyl, 
 35) —(CH 2 ) q —OC 2-6 alkenyl, 
 36) —(CH 2 ) q —OC 2-6 alkynyl, 
 37) —(CH 2 ) q —OC 3-6 cycloalkyl, 
 38) —(CH 2 ) q —OC 2-6 heterocycloalkyl, 
 39) —(CH 2 ) q —O-aryl, 
 40) —(CH 2 ) q —O-heteroaryl, 
 41) —OC 1-6 alkyl-C 3-6 cycloalkyl, 
 42) —OC 1-6 alkyl-C 2-6 heterocycloalkyl, 
 43) —OC 1-6 alkyl-aryl, 
 44) —OC 1-6 alkyl-heteroaryl, 
 45) —S(O) m R i , 
 46) —C 1-6 alkyl-S(O) m R i , 
 47) —C(O)R L , and 
 48) —NR k R L , 
 
       wherein each R b  is unsubstituted or substituted with one to six substituents selected from halogen, CF 3 , OCF 3 , CN, CH 2 CF 3 , CF 2 CH 3 , —C 1-6 alkyl, and —OC 1-6 alkyl; 
       R c  is selected from:
 1) —C 1-6 alkyl, 
 2) OH, 
 3) halogen, and 
 4) —OC 1-6 alkyl, 
 
       wherein alkyl is unsubstituted or substituted with one to three halogens; 
       R d  is selected from:
 1) —C 1-6 alkyl, 
 2) OH, 
 3) halogen, and 
 4) —OC 1-6 alkyl, 
 
       wherein alkyl is unsubstituted or substituted with one to three halogens; 
       R f  is selected from:
 1) —C 1-6 alkyl, 
 2) OH, 
 3) halogen, and 
 4) —OC 1-6 alkyl, 
 
       wherein alkyl is unsubstituted or substituted with one to three halogens; 
       R g  is selected from:
 1) —C 1-6 alkyl, 
 2) OH, 
 3) halogen, and 
 4) —OC 1-6 alkyl, 
 
       wherein alkyl is unsubstituted or substituted with one to three halogens; 
       R i  is selected from:
 1) hydrogen, 
 2) C 1-6 alkyl, 
 3) C 3-6 cycloalkyl, 
 4) aryl, and 
 5) heteroaryl; 
 
       R k  is selected from:
 1) hydrogen, and 
 2) C 1-6 alkyl; 
 
       R L  is selected from:
 1) hydrogen, 
 2) C 1-6 alkyl, 
 3) C 3-6 cycloalkyl, 
 4) aryl, and 
 5) heteroaryl; 
 
       m is independently selected from 0 to 2; 
       p is independently selected from 0 to 3; 
       q is independently selected from 0 to 3;
 b) a second compound selected from a calcium channel antagonist, or a pharmaceutically acceptable salt thereof, and 
 c) a pharmaceutically acceptable carrier. 
 
     
     
         2 - 4 . (canceled) 
     
     
         5 . The composition according to  claim 1  wherein in the first compound A is phenyl, wherein phenyl is unsubstituted or substituted with one to five substituents selected from R a ; or a pharmaceutically acceptable salt thereof. 
     
     
         6 - 9 . (canceled) 
     
     
         10 . The composition according to  claim 1  wherein in the first compound B is selected from the group consisting of:
 1) phenyl, 
 2) pyridine, 
 3) thiazole, and 
 4) cyclobutane, 
 
       wherein B is unsubstituted or substituted with one to five substituents selected from R b ; 
       or a pharmaceutically acceptable salt thereof. 
     
     
         11 . (canceled) 
     
     
         12 . The composition according to  claim 1  wherein in the first compound R 1 , R 2 , R 3 , R 4 , R 5 , R 6  and R 7  are each hydrogen; or a pharmaceutically acceptable salt thereof. 
     
     
         13 - 16 . (canceled) 
     
     
         17 . The composition according to  claim 1  wherein in the first compound
 A is selected from the group consisting of:
 1) phenyl, and 
 2) pyridine, 
 
 wherein each phenyl and pyridine is unsubstituted or substituted with one to five substituents selected from R a ; 
 B is selected from the group consisting of:
 1) phenyl, 
 2) pyridine, 
 3) thiazole, 
 4) pyrimidine, 
 5) pyrazine, 
 6) pyridazine, 
 7) imidazole, 
 8) pyrazole, 
 9) oxazole, 
 10) benzofuran, 
 11) benzo[d]oxazole, 
 12) benzo[d]thiazole, 
 13) indazole, 
 14) thiazolo[5,4-b]pyridine, 
 15) pyrazolo[1,5-a]pyridine, 
 16) —(CH 2 ) 2 -phenyl, 
 17) —CH 2 —O-phenyl, 
 18) —CH 2 —O-pyridine, 
 19) cyclobutane, 
 20) cyclohexane, 
 21) bicyclo[1.1.1]pentane, 
 22) spiro[3.3]heptane, 
 23) azetidine, 
 24) piperidine, 
 25) tetrahydropyran, 
 26) tetrahydrofuran, 
 27) azabicyclo[3.1.0]hexane, 
 28) —CH 2 -cyclohexane, 
 29) —CH 2 -tetrahydropyran, 
 30) —CH 2 —O-cyclohexane, and 
 31) bicyclo[4.2.0]octatriene, 
 
 wherein B is unsubstituted or substituted with one to five substituents selected from R b ; 
 R 1  is selected from the group consisting of:
 1) hydrogen, and 
 2) —C 1-6 alkyl, 
 
 wherein alkyl is unsubstituted or substituted with one to five substituents selected from R c ; 
 R 2  is selected from the group consisting of:
 1) hydrogen, and 
 2) —C 1-6 alkyl, 
 
 wherein alkyl is unsubstituted or substituted with one to five substituents selected from R d ; 
 R 3  is selected from the group consisting of:
 1) hydrogen, and 
 2) —C 1-6 alkyl, 
 
 wherein alkyl is unsubstituted or substituted with one to five substituents selected from R f ; 
 R 4  is selected from the group consisting of:
 1) hydrogen, and 
 2) —C 1-6 alkyl, 
 
 wherein alkyl is unsubstituted or substituted with one to five substituents selected from R g ; 
 R 6  is hydrogen, 
 R 7  is selected from the group consisting of:
 1) hydrogen, and 
 2) —C 1-6 alkyl, 
 
 wherein alkyl is unsubstituted or substituted with one to five halogen substituents; 
 each R a  is independently selected from the group consisting of:
 1) —CF 3 , 
 2) —OCF 3 , 
 3) —CHF 2 , 
 4) —OCH 2 CF 3 , 
 5) CN, 
 6) halogen, and 
 7) —C 2-6 alkynyl, 
 
 wherein each R a  is unsubstituted or substituted with one to six substituents selected from halogen, CF 3 , OH, C 1-6 alkyl, and —OC 1-6 alkyl; or a pharmaceutically acceptable salt thereof. 
 each R b  is independently selected from the group consisting of:
 1) —CF 3 , 
 2) —OCF 3 , 
 3) —CHF 2 , 
 4) —OCHF 2 , 
 5) —CH 2 CF 3 , 
 6) —CH(CF 3 )CH 3 , 
 7) —OCH 2 CF 3 , 
 8) CN, 
 9) halogen, 
 10) —S(O) 2 C 1-6 alkyl, 
 11) —C 1-6 alkyl, and 
 12) —C 3-6 cycloalkyl, 
 
 wherein each R b  is unsubstituted or substituted with one to six substituents selected from halogen, CF 3 , OCF 3 , CN, CH 2 CF 3 , CF 2 CH 3 , —C 1-6 alkyl, and O—C 1-6 alkyl; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         18 . The composition according to  claim 1  wherein in the first compound
 A is phenyl, wherein phenyl is unsubstituted or substituted with one to five substituents selected from R a ; 
 B is selected from the group consisting of:
 1) phenyl, 
 2) pyridine, 
 3) thiazole, and 
 4) cyclobutane, 
 
 wherein B is unsubstituted or substituted with one to five substituents selected from R b ; 
 R 1 , R 2 , R 3 , R 4 , R 5 , R 6  and R 7  are hydrogen; 
 each R a  is independently selected from the group consisting of:
 1) —CF 3 , 
 2) —OCF 3 , and 
 3) halogen; 
 
 each R b  is independently selected from the group consisting of:
 1) —CF 3 , 
 2) —OCF 3 , 
 3) —OCH 2 CF 3 , and 
 4) halogen, 
 
 wherein each R b  is unsubstituted or substituted with one to six substituents selected from halogen, CF 3 , OCF 3 , CN, CH 2 CF 3 , CF 2 CH 3 , —C 1-6 alkyl, and O—C 1-6 alkyl; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         19 . The composition according to  claim 1  wherein a) the first compound is selected from:
 1) (S)—N—((R)-2-(3-chloro-4-fluorophenoxy)-1-(3-chloro-4-fluorophenyl)ethyl)-2-oxoimidazolidine-4-carboxamide; 
 2) (S)—N—((S)-2-(3-chloro-4-fluorophenoxy)-1-(3-chloro-4-fluorophenyl)ethyl)-2-oxoimidazolidine-4-carboxamide; 
 3) (R)—N-(bis(4-chlorophenyl)methyl)-3-methyl-2-oxoimidazolidine-4-carboxamide and (S)—N-(bis(4-chlorophenyl)methyl)-3-methyl-2-oxoimidazolidine-4-carboxamide; 
 4) (S)—N—((R)-(5-chloro-6-(difluoromethyl)pyridin-2-yl)(5-chloro-6-(trifluoromethyl)pyridin-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 5) (S)—N—((S)-(5-chloro-6-(difluoromethyl)pyridin-2-yl)(5-chloro-6-(trifluoromethyl)pyridin-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 6) (S)—N—((R)-(3-chloro-4-fluorophenyl)(5-(trifluoromethyl)-1H-pyrazol-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 7) (S)—N—((S)-(3-chloro-4-fluorophenyl)(5-(trifluoromethyl)-1H-pyrazol-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 8) (S)—N—((R)-(3-chloro-2,4-difluorophenyl)(1-(1-(trifluoromethyl)cyclopropyl)piperidin-4-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 9) (S)—N—((S)-(3-chloro-2,4-difluorophenyl)(1-(1-(trifluoromethyl)cyclopropyl)piperidin-4-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 10) (S)—N-((5-chloro-4-(trifluoromethyl)pyrimidin-2-yl)(4-chlorophenyl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 11) (S)—N—((R)-(5-fluoro-6-(trifluoromethyl)pyridin-2-yl)(4-(trifluoromethoxy)phenyl)-methyl)-2-oxoimidazolidine-4-carboxamide; 
 12) (S)—N—((S)-(5-fluoro-6-(trifluoromethyl)pyridin-2-yl)(4-(trifluoromethoxy)phenyl)-methyl)-2-oxoimidazolidine-4-carboxamide; 
 13) (S)—N—((R)-(3-chloro-2,4-difluorophenyl)((trans)-5-(trifluoromethyl)tetrahydro-2H-pyran-2-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 14) (S)—N—((S)-(3-chloro-2,4-difluorophenyl)((trans)-5-(trifluoromethyl)tetrahydro-2H-pyran-2-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 15) (S)—N—((R)-(3-chlorophenyl)(4-(trifluoromethoxy)phenyl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 16) (S)—N—((S)-(3-chlorophenyl)(4-(trifluoromethoxy)phenyl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 17) (R)—N-[bis(4-chlorophenyl)methyl]-1-methyl-2-oxoimidazolidine-4-carboxamide; 
 18) (S)—N-[bis(4-chlorophenyl)methyl]-1-methyl-2-oxoimidazolidine-4-carboxamide; 
 19) (4S)—N—{((R)-3-chloro-4-fluorophenyl)[5-fluoro-6-(2,2,2-trifluoro-ethoxy)pyridin-2-yl]methyl}-2-oxoimidazolidine-4-carboxamide; 
 20) (4S)—N—{((S)-3-chloro-4-fluorophenyl)[5-fluoro-6-(2,2,2-trifluoro-ethoxy)pyridin-2-yl]methyl}-2-oxoimidazolidine-4-carboxamide; 
 21) (4S)—N—[((R)-3-chloro-4-fluorophenyl)(6-cyanopyridin-2-yl)methyl]-2-oxoimidazolidine-4-carboxamide; 
 22) (4S)—N—[((S)-3-chloro-4-fluorophenyl)(6-cyanopyridin-2-yl)methyl]-2-oxoimidazolidine-4-carboxamide; 
 23) (4S)—N—[((R)-5-chloro-6-cyclopropylpyridin-3-yl)(3-chloro-2,4-difluoro-phenyl)methyl]-2-oxoimidazolidine-4-carboxamide; 
 24) (4S)—N—[((S)-5-chloro-6-cyclo-propylpyridin-3-yl)(3-chloro-2,4-difluoro-phenyl)methyl]-2-oxoimidazolidine-4-carboxamide; 
 25) (4S)—N—{[(R)-5-chloro-6-(trifluoromethyl)pyridin-3-yl][5-fluoro-6-(trifluoro-methyl)pyridin-2-yl]methyl}-2-oxoimidazolidine-4-carboxamide; 
 26) (4S)—N—{[(S)-5-chloro-6-(trifluoromethyl)pyridin-3-yl][5-fluoro-6-(trifluoro-methyl)pyridin-2-yl]methyl}-2-oxoimidazolidine-4-carboxamide; 
 27) (S)—N—((R)-(3-chloro-4-fluorophenyl)(cis-2,6-dimethyl-1-(2,2,2-trifluoroethyl)-piperidin-4-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 28) (S)—N—((S)-(3-chloro-4-fluorophenyl)(cis-2,6-dimethyl-1-(2,2,2-trifluoroethyl)-piperidin-4-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 29) (S)—N—((R)-(3-chloro-4-fluorophenyl)(2-(1-(trifluoromethyl)cyclopropyl)thiazol-4-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 30) (S)—N—((S)-(3-chloro-4-fluorophenyl)(2-(1-(trifluoromethyl)cyclopropyl)thiazol-4-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 31) (S)—N—((R)-(4-chlorophenyl)(4-fluoro-3-(trifluoro-methyl)phenyl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 32) (S)—N—((S)-(4-chlorophenyl)(4-fluoro-3-(trifluoro-methyl)phenyl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 33) (S)—N—((R)-(3-chloro-4-fluoro-phenyl)(4-cyano-phenyl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 34) (S)—N—((S)-(3-chloro-4-fluoro-phenyl)(4-cyano-phenyl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 35) (S)-2-oxo-N—((R)-(6-(trifluoromethyl)pyridin-3-yl)(2-(trifluoromethyl)thiazol-4-yl)methyl)imidazolidine-4-carboxamide; 
 36) (S)-2-oxo-N—((S)-(6-(trifluoromethyl)pyridin-3-yl)(2-(trifluoromethyl)thiazol-4-yl)methyl)imidazolidine-4-carboxamide; 
 37) (R)—N-(bis(4-chlorophenyl)methyl)-4-methyl-2,5-dioxoimidazolidine-4-carboxamide; 
 38) (S)—N-(bis(4-chlorophenyl)methyl)-4-methyl-2,5-dioxoimidazolidine-4-carboxamide; 
 39) (R)—N-(bis(4-chlorophenyl)methyl)-3-(2-hydroxyethyl)-2-oxoimidazolidine-4-carboxamide; 
 40) (S)—N-(bis(4-chlorophenyl)methyl)-3-(2-hydroxyethyl)-2-oxoimidazolidine-4-carboxamide; 
 41) (S)—N—((R)-(4-chlorophenyl)(2-(trifluoromethyl)-1H-imidazol-4-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 42) (S)—N—((S)-(4-chlorophenyl)(2-(trifluoromethyl)-1H-imidazol-4-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 43) (S)—N—((R)-1-(3-chloro-2,4-difluorophenyl)-2-((cis)-4-(trifluoromethyl)cyclohexyl)ethyl)-2-oxoimidazolidine-4-carboxamide; 
 44) (S)—N—((R)-1-(3-chloro-2,4-difluorophenyl)-2-((trans)-4-(trifluoromethyl)cyclohexyl)-ethyl)-2-oxoimidazolidine-4-carboxamide; 
 45) (S)—N—((S)-1-(3-chloro-2,4-difluorophenyl)-2-((trans)-4-(trifluoromethyl)cyclohexyl)-ethyl)-2-oxoimidazolidine-4-carboxamide; 
 46) (S)—N—((S)-1-(3-chloro-2,4-difluorophenyl)-2-((cis)-4-(trifluoromethyl)cyclohexyl)ethyl)-2-oxoimidazolidine-4-carboxamide; 
 47) (4S)—N—{(R)-(3-chloro-2,4-difluorophenyl)[6-(trifluoromethoxy)pyridin-3-yl]methyl}-2-oxoimidazolidine-4-carboxamide; 
 48) (4S)—N—{(S)-(3-chloro-2,4-difluorophenyl)[6-(trifluoromethoxy)pyridin-3-yl]methyl}-2-oxoimidazolidine-4-carboxamide; 
 49) (S)—N—((R)-1-(3-chloro-2,4-difluorophenyl)-2-(4,4-difluorocyclohexyl)ethyl)-2-oxoimidazolidine-4-carboxamide; 
 50) (S)—N—((S)-1-(3-chloro-2,4-difluorophenyl)-2-(4,4-difluorocyclohexyl)ethyl)-2-oxoimidazolidine-4-carboxamide; 
 51) (S)—N—((R)-1-(3-chloro-2,4-difluorophenyl)-2-((R)-tetrahydro-2H-pyran-3-yl)ethyl)-2-oxoimidazolidine-4-carboxamide; 
 52) (S)—N—((R)-1-(3-chloro-2,4-difluorophenyl)-2-((S)-tetrahydro-2H-pyran-3-yl)ethyl)-2-oxoimidazolidine-4-carboxamide; 
 53) (S)—N—((S)-1-(3-chloro-2,4-difluorophenyl)-2-((R)-tetrahydro-2H-pyran-3-yl)ethyl)-2-oxoimidazolidine-4-carboxamide; 
 54) (S)—N—((S)-1-(3-chloro-2,4-difluorophenyl)-2-((S)-tetrahydro-2H-pyran-3-yl)ethyl)-2-oxoimidazolidine-4-carboxamide; 
 55) (S)—N—((R)-(3-chloro-2,4-difluorophenyl)(3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 56) (S)—N—((S)-(3-chloro-2,4-difluorophenyl)(3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 57) (4S)—N—{(R)-(3-chloro-4-fluorophenyl)[1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl]methyl}-2-oxoimidazolidine-4-carboxamide; 
 58) (4S)—N—{(S)-(3-chloro-4-fluorophenyl)[1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl]methyl}-2-oxoimidazolidine-4-carboxamide; 
 59) (4S)—N-{1-((R)-3-chloro-4-fluorophenyl)-2-[(4,4-difluoro-cyclohexyl)oxy]ethyl}-2-oxoimidazolidine-4-carboxamide; 
 60) (4S)—N-{1-((S)-3-chloro-4-fluorophenyl)-2-[(4,4-difluoro-cyclohexyl)oxy]ethyl}-2-oxoimidazolidine-4-carboxamide; 
 61) (4S)—N—[(R)-(3-chloro-2,4-di-fluorophenyl)(3,3-dimethylcyclobutyl)methyl]-2-oxoimidazolidine-4-carboxamide; 
 62) (4S)—N—[(S)-(3-chloro-2,4-di-fluorophenyl)(3,3-dimethylcyclobutyl)methyl]-2-oxoimidazolidine-4-carboxamide; 
 63) (S)—N—((R)-(3-chloro-4-fluorophenyl)(1-methyl-3-(tri-fluoromethyl)-1H-pyrazol-5-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 64) (S)—N—((S)-(3-chloro-4-fluorophenyl)(1-methyl-3-(tri-fluoromethyl)-1H-pyrazol-5-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 65) (S)—N—((R)-(3-chloro-4-fluorophenyl)(trans-4-(trifluoromethyl)cyclohexyl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 66) (S)—N—((S)-(3-chloro-4-fluorophenyl)(trans-4-(trifluoromethyl)cyclohexyl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 67) (S)—N—((R)-(3-chloro-2,4-difluorophenyl)(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 68) (S)—N—((S)-(3-chloro-2,4-difluorophenyl)(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 69) (S)—N—((R)-(3-chloro-2,4-difluorophenyl)(trans-3-(trifluoromethyl)cyclobutyl)-methyl)-2-oxoimidazolidine-4-carboxamide; 
 70) (S)—N—((S)-(3-chloro-2,4-difluorophenyl)(trans-3-(trifluoromethyl)cyclobutyl)-methyl)-2-oxoimidazolidine-4-carboxamide; 
 71) (S)—N—((R)-(3-chloro-2,4-difluorophenyl)(2-(2,2,2-trifluoroethoxy)thiazol-5-yl)-methyl)-2-oxoimidazolidine-4-carboxamide; 
 72) (S)—N—((S)-(3-chloro-2,4-difluorophenyl)(2-(2,2,2-trifluoroethoxy)thiazol-5-yl)-methyl)-2-oxoimidazolidine-4-carboxamide; 
 73) (S)—N—((R)-(3-chloro-2,4-difluorophenyl)(2-(difluoromethoxy)thiazol-5-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 74) (S)—N—((S)-(3-chloro-2,4-difluorophenyl)(2-(difluoromethoxy)thiazol-5-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 75) (S)—N—((R)-(3-chloro-2,4-difluorophenyl)(6,6-difluorospiro[3.3]heptan-2-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 76) (S)—N—((S)-(3-chloro-2,4-difluorophenyl)(6,6-difluorospiro[3.3]heptan-2-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 77) (S)—N—((R)-(3-chloro-2,4-difluorophenyl)(5-chloro-6-(trifluoromethyl)pyridin-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 78) (S)—N—((S)-(3-chloro-2,4-difluorophenyl)(5-chloro-6-(trifluoromethyl)pyridin-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 79) (S)—N—((R)-(3-chloro-2,4-difluorophenyl)(trans-3-(trifluoromethyl)cyclobutyl)-methyl)-2-oxoimidazolidine-4-carboxamide; 
 80) (S)—N—((S)-(3-chloro-2,4-difluorophenyl)(trans-3-(trifluoromethyl)cyclobutyl)-methyl)-2-oxoimidazolidine-4-carboxamide; 
 81) (S)—N—((R)-3-chloro-4-(trifluoromethoxy)phenyl)(5-(trifluoromethoxy)pyridin-2-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 82) (S)—N—((S)-3-chloro-4-(trifluoromethoxy)phenyl)(5-(trifluoromethoxy)pyridin-2-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 83) (S)—N—((R)-(5-chloro-6-cyclopropylpyridin-2-yl)(4-(trifluoromethoxy)phenyl)-methyl)-2-oxoimidazolidine-4-carboxamide; 
 84) (S)—N—((S)-(5-chloro-6-cyclopropylpyridin-2-yl)(4-(trifluoromethoxy)phenyl)-methyl)-2-oxoimidazolidine-4-carboxamide; 
 85) (S)—N—((R)-(3-chloro-4-(trifluoromethoxy)phenyl)(1-(trifluoromethyl)-1H-pyrazol-4-yl)-l3-methyl)-2-oxoimidazolidine-4-carboxamide; 
 86) (S)—N—((S)-(3-chloro-4-(trifluoromethoxy)phenyl)(1-(trifluoromethyl)-1H-pyrazol-4-yl)-l3-methyl)-2-oxoimidazolidine-4-carboxamide; 
 87) (S)—N—((R)-(3-chloro-2,4-difluorophenyl)(6-(difluoromethoxy)-5-fluoropyridin-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 88) (S)—N—((S)-(3-chloro-2,4-difluorophenyl)(6-(difluoromethoxy)-5-fluoropyridin-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 89) (S)—N—((R)-(3-chloro-2,4-difluorophenyl)(6-(difluoromethyl)pyridin-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 90) (S)—N—((S)-(3-chloro-2,4-difluorophenyl)(6-(difluoromethyl)pyridin-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 91) (S)—N—((R)-(3-chloro-2,4-difluorophenyl)(5-fluoro-6-(trifluoromethyl)pyridin-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 92) (S)—N—((S)-(3-chloro-2,4-difluorophenyl)(5-fluoro-6-(trifluoromethyl)pyridin-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 93) (S)—N—((R)-(5-fluoro-6-(trifluoro-methyl)pyridin-2-yl)(6-(trifluoromethoxy)pyridin-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 94) (S)—N—((S)-(5-fluoro-6-(trifluoromethyl)pyridin-2-yl)(6-(trifluoromethoxy)pyridin-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 95) (S)—N—((R)-(5-fluoro-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)(5-fluoro-6-(trifluoro-methyl)pyridin-2-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 96) (S)—N—((S)-(5-fluoro-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)(5-fluoro-6-(trifluoro-methyl)-pyridin-2-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 97) (S)—N—((R)-(3-chloro-4-(trifluoromethoxy)phenyl)(2-(trifluoromethyl)oxazol-4-yl)methyl)-2-oxoimidazolidine-4-carboxamide 
 98) (S)—N—((S)-(3-chloro-4-(trifluoromethoxy)phenyl)(2-(trifluoromethyl)oxazol-4-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 99) (S)—N—((R)-(3-chloro-2,4-difluorophenyl)(2-(trifluoromethyl)pyrimidin-5-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 100) (S)—N—((S)-(3-chloro-2,4-difluorophenyl)(2-(trifluoromethyl)pyrimidin-5-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 101) (S)—N—((R)-3-chloro-4-(trifluoromethoxy)phenyl)(2-(trifluoromethyl)pyrimidin-4-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 102) (S)—N—((S)-3-chloro-4-(trifluoromethoxy)phenyl)(2-(trifluoromethyl)pyrimidin-4-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 103) (4S)—N—((R)-(3-chloro-2,4-difluorophenyl)(6-(2,2,2-trifluoroethoxy)pyridazin-3-yl)-methyl)-2-oxoimidazolidine-4-carboxamide; 
 104) (4S)—N—((S)-(3-chloro-2,4-difluorophenyl)(6-(2,2,2-trifluoroethoxy)pyridazin-3-yl)-methyl)-2-oxoimidazolidine-4-carboxamide; 
 105) (4S)—N—((R)-(3-chloro-2,4-difluorophenyl)(5-(2,2,2-trifluoroethoxy)pyrazin-2-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 106) (4S)—N—((S)-(3-chloro-2,4-difluorophenyl)(5-(2,2,2-trifluoroethoxy)pyrazin-2-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 107) (S)—N—((R)-1-(3-chloro-2,4-difluorophenyl)-3-(4-chlorophenyl)propyl)-2-oxo-imidazolidine-4-carboxamide; 
 108) (S)—N—((S)-1-(3-chloro-2,4-difluorophenyl)-3-(4-chlorophenyl)propyl)-2-oxo-imidazolidine-4-carboxamide; 
 109) (4S)—N-(1-(3-chloro-4-fluorophenyl)-2-((6-(trifluoromethyl)pyridin-3-yl)oxy)ethyl)-2-oxoimidazolidine-4-carboxamide; 
 110) (S)—N—((R)-1-(3-chloro-2,4-difluorophenyl)-2-cyclohexylethyl)-2-oxoimidazolidine-4-carboxamide; 
 111) (S)—N—((S)-1-(3-chloro-2,4-difluorophenyl)-2-cyclohexylethyl)-2-oxoimidazolidine-4-carboxamide; 
 112) (4S)—N—((R)-(3-chloro-2,4-difluorophenyl)(2-(difluoromethoxy)pyrimidin-5-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 113) (4S)—N—((S)-(3-chloro-2,4-difluorophenyl)(2-(difluoromethoxy)pyrimidin-5-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 114) (S)—N—((R)-(5-chloro-6-(trifluoromethyl)pyridin-2-yl)(5-chloro-6-(trifluoromethyl)-pyridin-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 115) (S)—N—((S)-(5-chloro-6-(trifluoromethyl)pyridin-2-yl)(5-chloro-6-(trifluoromethyl)-pyridin-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 116) (S)—N—((R)-(4-chloro-3-cyanophenyl)(4-(trifluoromethoxy)phenyl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 117) (S)—N—((S)-(4-chloro-3-cyanophenyl)(4-(trifluoromethoxy)phenyl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 118) (S)—N—((R)-(3-chloro-2,4-difluorophenyl)((R)-1-(2,2,2-trifluoroethyl)piperidin-2-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 119) (S)—N—((R)-(3-chloro-2,4-difluorophenyl)((S)-1-(2,2,2-trifluoroethyl)piperidin-2-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 120) (S)—N—((S)-(3-chloro-2,4-difluorophenyl)((S)-1-(2,2,2-trifluoroethyl)piperidin-2-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 121) (S)—N—((S)-(3-chloro-4-fluoro-phenyl)((S)-2-chlorobicyclo[4.2.0]-octa-1(6),2,4-trien-7-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 122) (S)—N—((R)-(4-chlorophenyl)(5-fluoro-4-(trifluoromethyl)pyridin-2-yl)methyl)-2-oxo-imidazolidine-4-carboxamide; 
 123) (S)—N—((S)-(4-chlorophenyl)(5-fluoro-4-(trifluoromethyl)pyridin-2-yl)methyl)-2-oxo-imidazolidine-4-carboxamide; 
 124) (S)—N—((R)-(4-chloro-3-(trifluoromethyl)-phenyl)(4-cyanophenyl)-methyl)-2-oxo-imidazolidine-4-carboxamide; 
 125) (S)—N—((S)-(4-chloro-3-(trifluoromethyl)-phenyl)(4-cyanophenyl)-methyl)-2-oxo-imidazolidine-4-carboxamide; 
 126) (S)—N-(bis(3-chloro-4-fluorophenyl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 127) (S)—N—((R)-(3-chloro-4-fluorophenyl)(5-chloro-6-(trifluoromethyl)pyridin-2-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 128) (S)—N—((S)-(3-chloro-4-fluorophenyl)(5-chloro-6-(trifluoromethyl)pyridin-2-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 129) (S)—N—((R)-(3-chloro-2,4-difluorophenyl)(6-(difluoromethyl)-5-fluoropyridin-2-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 130) (S)—N—((S)-(3-chloro-2,4-difluorophenyl)(6-(difluoromethyl)-5-fluoropyridin-2-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 131) (S)—N—((R)-(3-chloro-2,4-difluorophenyl)(2-(difluoromethoxy)pyrimidin-5-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 132) (S)—N—((S)-(3-chloro-2,4-difluorophenyl)(2-(difluoromethoxy)pyrimidin-5-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 133) (S)—N—((R)-(3-chloro-2,4-difluorophenyl)(3-methyl-1-((S)-1,1,1-trifluoropropan-2-yl)azetidin-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 134) (S)—N—((R)-(3-chloro-2,4-difluorophenyl)(3-methyl-1-((R)-1,1,1-trifluoropropan-2-yl)azetidin-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 135) (S)—N—((S)-(3-chloro-2,4-difluorophenyl)(3-methyl-1-((S)-1,1,1-trifluoropropan-2-yl)azetidin-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 136) (S)—N—((S)-(3-chloro-2,4-difluorophenyl)(3-methyl-1-((R)-1,1,1-trifluoropropan-2-yl)azetidin-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 137) (S)—N—((R)-(3-chloro-4-fluorophenyl)(2-methylbenzo[d]thiazol-5-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 138) (S)—N—((S)-(3-chloro-4-fluorophenyl)(2-methylbenzo[d]thiazol-5-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 139) (S)—N—((R)-(3-chloro-4-fluorophenyl)(trans-2-(trifluoromethyl)cyclobutyl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 140) (S)—N—((S)-(3-chloro-4-fluorophenyl)(trans-2-(trifluoromethyl)cyclobutyl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 141) (4S)—N-((3-chloro-4-fluorophenyl)(3,3-dimethyl-2-(trifluoromethyl)cyclobutyl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 142) (4S)—N-((3-chloro-4-fluorophenyl)(4-fluorobicyclo[4.2.0]octa-1(6),2,4-trien-7-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 143) (S)—N—((R)-(3-chloro-4-fluoro-phenyl)((R)-2-chlorobicyclo[4.2.0]-octa-1(6),2,4-trien-7-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 144) (S)—N—((R)-(3-chloro-4-fluoro-phenyl)((S)-2-chlorobicyclo[4.2.0]-octa-1(6),2,4-trien-7-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 145) (S)—N—((S)-(3-chloro-4-fluoro-phenyl)((R)-2-chlorobicyclo[4.2.0]-octa-1(6),2,4-trien-7-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 146) (S)—N—((S)-(3-chloro-4-fluoro-phenyl)((S)-2-chlorobicyclo[4.2.0]-octa-1(6),2,4-trien-7-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 147) (S)—N—((R)-(3-chloro-4-fluoro-phenyl)((R)-2-chlorobicyclo[4.2.0]-octa-1(6),2,4-trien-7-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 148) (S)—N—((R)-(3-chloro-4-fluoro-phenyl)((S)-2-chlorobicyclo[4.2.0]-octa-1(6),2,4-trien-7-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 149) (S)—N—((S)-(3-chloro-4-fluoro-phenyl)((R)-2-chlorobicyclo[4.2.0]-octa-1(6),2,4-trien-7-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 150) (S)—N—((S)-(3-chloro-4-fluoro-phenyl)((S)-2-chlorobicyclo[4.2.0]-octa-1(6),2,4-trien-7-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 151) (4S)—N-((3-chloro-4-fluorophenyl)(4-chlorobicyclo[4.2.0]-octa-1(6),2,4-trien-7-yl)-methyl)-2-oxoimidazolidine-4-carboxamide; 
 152) (4S)—N-((3-chloro-4-fluorophenyl)(thiazolo[5,4-b]pyridin-2-yl)methyl)-2-oxo-imidazolidine-4-carboxamide; 
 153) (S)—N—((R)-(3-chloro-4-fluorophenyl)(5-chlorobenzofuran-2-yl)methyl)-2-oxo-imidazolidine-4-carboxamide; 
 154) (S)—N—((S)-(3-chloro-4-fluorophenyl)(5-chlorobenzofuran-2-yl)methyl)-2-oxo-imidazolidine-4-carboxamide; 
 155) (S)—N—((R)-(4-chlorophenyl)(6-(difluoromethoxy)pyridin-2-yl)methyl)-2-oxo-imidazolidine-4-carboxamide; 
 156) (S)—N—((S)-(4-chlorophenyl)(6-(difluoromethoxy)pyridin-2-yl)methyl)-2-oxo-imidazolidine-4-carboxamide; 
 157) (S)—N—((R)-(4-chlorophenyl)(1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 158) (S)—N—((S)-(4-chlorophenyl)(1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 159) (4S)—N-((4-chlorophenyl)(4-methyl-2-(trifluoro-methyl)thiazol-5-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 160) (4S)—N-((1(R))-(3-chloro-4-fluorophenyl)(3-(2,2,2-trifluoroethyl)-3-azabicyclo-[3.1.0]hexan-6-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 161) (4S)—N-((1(S))-(3-chloro-4-fluorophenyl)(3-(2,2,2-trifluoroethyl)-3-azabicyclo-[3.1.0]-hexan-6-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 162) (S)—N—((R)-(3-chloro-2,4-difluorophenyl)((cis)-1-methyl-2-(trifluoro-methyl)piperidin-4-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 163) (S)—N—((R)-(3-chloro-2,4-difluorophenyl)((trans)-1-methyl-2-(trifluoro-methyl)piperidin-4-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 164) (S)—N—((S)-(3-chloro-2,4-difluorophenyl)((cis)-1-methyl-2-(trifluoro-methyl)-piperidin-4-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 165) (S)—N—((S)-(3-chloro-2,4-difluorophenyl)((trans)-1-methyl-2-(trifluoro-methyl)-piperidin-4-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 166) (S)—N—((R)-(3-chloro-2,4-difluorophenyl)((cis)-5-(trifluoromethyl)-tetrahydrofuran-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 167) S)—N—((R)-(3-chloro-2,4-difluorophenyl)((trans)-5-(trifluoromethyl)-tetrahydrofuran-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 168) (S)—N—((S)-(3-chloro-2,4-difluorophenyl)((cis)-5-(trifluoromethyl)-tetrahydrofuran-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 169) (S)—N—((S)-(3-chloro-2,4-difluorophenyl)((trans)-5-(trifluoromethyl)-tetrahydrofuran-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 170) (S)—N—((R)-(4-chlorophenyl)(pyrazolo[1,5-a]pyridin-5-yl)methyl)-2-oxo-imidazolidine-4-carboxamide; 
 171) (S)—N—((S)-(4-chlorophenyl)(pyrazolo[1,5-a]pyridin-5-yl)methyl)-2-oxo-imidazolidine-4-carboxamide; 
 172) (4S)—N-(benzo[d]thiazol-6-yl(4-chlorophenyl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 173) (S)—N—((R)-(4-chlorophenyl)(1H-indazol-6-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 174) (S)—N—((S)-(4-chlorophenyl)(1H-indazol-6-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 175) (S)—N—((R)-(4-chlorophenyl)(pyrazolo[1,5-a]pyridin-5-yl)methyl)-2-oxo-imidazolidine-4-carboxamide; 
 176) (S)—N—((S)-(4-chlorophenyl)(pyrazolo[1,5-a]pyridin-5-yl)methyl)-2-oxo-imidazolidine-4-carboxamide; 
 177) (S)—N—((R)-(4-chlorophenyl)(2-methylbenzo[d]oxazol-6-yl)methyl)-2-oxo-imidazolidine-4-carboxamide; 
 178) (S)—N—((S)-(4-chlorophenyl)(2-methylbenzo[d]oxazol-6-yl)methyl)-2-oxo-imidazolidine-4-carboxamide; 
 179) (S)—N—((R)-(4-chlorophenyl)(2-methylbenzo[d]thiazol-6-yl)methyl)-2-oxo-imidazolidine-4-carboxamide; 
 180) (S)—N—((S)-(4-chlorophenyl)(2-methylbenzo[d]thiazol-6-yl)methyl)-2-oxo-imidazolidine-4-carboxamide; 
 181) (S)—N—((R)-(3-chloro-4-fluorophenyl)(4-(methylsulfonyl)phenyl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 182) (S)—N—((S)-(3-chloro-4-fluorophenyl)(4-(methylsulfonyl)phenyl)methyl)-2-oxo-imidazolidine-4-carboxamide; 
 183) (4S)—N-[(3-chloro-4-fluorophenyl)(5-cyanopyridin-2-yl)methyl]-2-oxoimidazolidine-4-carboxamide; 
 184) (S)—N—((R)-benzo[d]thiazol-2-yl(3-chloro-4-fluoro-phenyl)methyl)-2-oxo-imidazolidine-4-carboxamide; 
 185) (S)—N—((S)-benzo[d]thiazol-2-yl(3-chloro-4-fluoro-phenyl)methyl)-2-oxo-imidazolidine-4-carboxamide; 
 186) (S)—N—((R)-benzo[d]oxazol-2-yl(3-chloro-4-fluoro-phenyl)methyl)-2-oxo-imidazolidine-4-carboxamide; 
 187) (S)—N—((S)-benzo[d]oxazol-2-yl(3-chloro-4-fluoro-phenyl)methyl)-2-oxo-imidazolidine-4-carboxamide; 
 188) (S)—N—((R)-(8,8-difluorobicyclo[4.2.0]octa-1(6),2,4-trien-3-yl)(4-(trifluoromethoxy)-phenyl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 189) (S)—N—((S)-(8,8-difluorobicyclo[4.2.0]octa-1(6),2,4-trien-3-yl)(4-(trifluoromethoxy)-phenyl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 190) (S)—N—((R)-(4-chlorophenyl)(7,7-difluorobicyclo[4.2.0]octa-1(6),2,4-trien-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 (191) (S)—N—((S)-(4-chlorophenyl)(7,7-difluorobicyclo[4.2.0]octa-1(6),2,4-trien-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 192) (4S)—N—((R)(4-chlorophenyl)((R)2,2-dimethyl-1-(2,2,2-trifluoroethyl)piperidin-4-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 193) (4S)—N—((R)(4-chlorophenyl)((S)2,2-dimethyl-1-(2,2,2-trifluoroethyl)piperidin-4-yl)methyl)-2-oxoimidazolidine-4-carboxamide; 
 194) (4S)—N—((S)(4-chlorophenyl)((S)2,2-dimethyl-1-(2,2,2-trifluoroethyl)piperidin-4-yl)methyl)-2-oxoimidazolidine-4-carboxamide; and 
 195) (4S)—N—((S)(4-chlorophenyl)((R)2,2-dimethyl-1-(2,2,2-trifluoroethyl)piperidin-4-yl)methyl)-2-oxoimidazolidine-4-carboxamide;
 b) the second compound is a calcium channel antagonist selected from: amlodipine, diltiazem, felodipine, gabapentin, isradipine, nicardipine, nifedipine, nisoldipine, pregabalin, verapamil, and ziconotide; or a pharmaceutically acceptable salt thereof. 
 
 
     
     
         20 - 30 . (canceled) 
     
     
         31 . The composition according to  claim 19  wherein
 a) the first compound is (S)—N—((R)-(3-chlorophenyl)(4-(trifluoromethoxy)phenyl)-methyl)-2-oxoimidazolidine-4-carboxamide; and 
 b) the second compound is gabapentin or pregabalin. 
 
     
     
         32 . The composition according to  claim 19  wherein
 a) the first compound is (S)—N—((S)-(3-chlorophenyl)(4-(trifluoromethoxy)phenyl)methyl)-2-oxoimidazolidine-4-carboxamide; and 
 b) the second compound is gabapentin or pregabalin. 
 
     
     
         33 . The composition according to  claim 19  wherein
 a) the first compound is (S)—N—((R)-(5-fluoro-6-(trifluoromethyl)pyridin-2-yl)(4-(trifluoromethoxy)phenyl)methyl)-2-oxoimidazolidine-4-carboxamide; and 
 b) the second compound is gabapentin or pregabalin. 
 
     
     
         34 . The composition according to  claim 19  wherein
 a) the first compound is (S)—N—((S)-(5-fluoro-6-(trifluoromethyl)pyridin-2-yl)(4-(trifluoromethoxy)phenyl)methyl)-2-oxoimidazolidine-4-carboxamide; and 
 b) the second compound is gabapentin or pregabalin. 
 
     
     
         35 . The composition according to  claim 19  wherein
 a) the first compound is (S)—N—((R)-(3-chloro-2,4-difluorophenyl)(trans-3-(trifluoromethyl)cyclobutyl)-methyl)-2-oxoimidazolidine-4-carboxamide; and 
 b) the second compound is gabapentin or pregabalin. 
 
     
     
         36 . The composition according to  claim 19  wherein
 a) the first compound is (S)—N—((S)-(3-chloro-2,4-difluorophenyl)(trans-3-(trifluoro-methyl)cyclobutyl)-methyl)-2-oxoimidazolidine-4-carboxamide; and 
 b) the second compound is gabapentin or pregabalin. 
 
     
     
         37 . The composition according to  claim 1  wherein the calcium channel antagonist is selected from: amlodipine, diltiazem, felodipine, gabapentin, isradipine, nicardipine, nifedipine, nisoldipine, pregabalin, verapamil, and ziconotide; or a pharmaceutically acceptable salt thereof. 
     
     
         38 . The composition according to  claim 1  wherein the calcium channel antagonist is gabapentin; or a pharmaceutically acceptable salt thereof. 
     
     
         39 . The composition according to  claim 1  wherein the calcium channel antagonist is pregabalin; or a pharmaceutically acceptable salt thereof. 
     
     
         40 . A method of treating a disorder selected from: nociception, osteoarthritis, peripheral neuropathy, inherited erythromelalgia, multiple sclerosis, asthma, itch, atopy, allergic dermatitis, contact dermatitis, renal failure, cholestasis, pruritus, migraine, neurodegeneration following ischemia, epilepsy, spontaneous pain, acute pain due to fractures, musculoskeletal damage, pancreatitis and renal colic, pre-operative pain, peri-operative pain, post-operative pain, post herpetic neuralgia, trigeminal neuralgia, diabetic neuropathy, chronic lower back pain, phantom limb pain, sciatica, pain caused by 2° or 3° burn injury, burning mouth syndrome, optic neuritis, pain resulting from cancer and chemotherapy, chronic pelvic pain, pain syndromes, and complex regional pain syndromes, central pain syndromes, post surgical pain syndromes, post mastectomy syndrome, post thoracotomy syndrome, stump pain, bone and joint pain, vulvodynia, pain associated with HIV, and HIV treatment-induced neuropathy, nerve injury, root avulsions, painful traumatic mononeuropathy, painful polyneuropathy, erythromelalgia, paroxysmal extreme pain disorder, small fiber neuropathy, repetitive motion pain, dental pain, myofascial pain, muscular injury, fibromyalgia, chronic pain, dysmenorrhea, pain associated with angina, shoulder tendonitis, bursitis, gouty arthritis, polymyalgia rheumatica, primary hyperalgesia, secondary hyperalgesia, primary allodynia, secondary allodynia, pain caused by central sensitization, chronic arthritic pain, cluster headache, non-vascular headache, traumatic nerve injury, nerve compression, nerve entrapment, and neuroma pain in a patient in need thereof comprising administration of a therapeutically effective amount of the composition according to  claim 1 . 
     
     
         41 . The method of  claim 40  wherein the disorder is selected from: chronic pain, osteoarthritis, peripheral neuropathy, acute pain due to fractures, musculoskeletal damage, pancreatitis and renal colic, pre-operative pain, peri-operative pain, post-operative pain, diabetic neuropathy, chronic lower back pain, pain resulting from chemotherapy, gouty arthritis, polymyalgia rheumatica, bone and joint pain, myofascial pain, muscular injury, fibromyalgia, shoulder tendonitis, and bursitis. 
     
     
         42 . The method of  claim 41  wherein the disorder is selected from: chronic pain, osteoarthritis, peripheral neuropathy, diabetic neuropathy, and chronic lower back pain. 
     
     
         43 . A method of treating a disorder selected from: nociception, osteoarthritis, peripheral neuropathy, inherited erythromelalgia, multiple sclerosis, asthma, itch, atopy, allergic dermatitis, contact dermatitis, renal failure, cholestasis, pruritus, migraine, neurodegeneration following ischemia, epilepsy, spontaneous pain, acute pain due to fractures, musculoskeletal damage, pancreatitis and renal colic, pre-operative pain, peri-operative pain, post-operative pain, post herpetic neuralgia, trigeminal neuralgia, diabetic neuropathy, chronic lower back pain, phantom limb pain, sciatica, pain caused by 2° or 3° burn injury, burning mouth syndrome, optic neuritis, pain resulting from cancer and chemotherapy, chronic pelvic pain, pain syndromes, and complex regional pain syndromes, central pain syndromes, post surgical pain syndromes, post mastectomy syndrome, post thoracotomy syndrome, stump pain, bone and joint pain, vulvodynia, pain associated with HIV, and HIV treatment-induced neuropathy, nerve injury, root avulsions, painful traumatic mononeuropathy, painful polyneuropathy, erythromelalgia, paroxysmal extreme pain disorder, small fiber neuropathy, repetitive motion pain, dental pain, myofascial pain, muscular injury, fibromyalgia, chronic pain, dysmenorrhea, pain associated with angina, shoulder tendonitis, bursitis, gouty arthritis, polymyalgia rheumatica, primary hyperalgesia, secondary hyperalgesia, primary allodynia, secondary allodynia, pain caused by central sensitization, chronic arthritic pain, cluster headache, non-vascular headache, traumatic nerve injury, nerve compression, nerve entrapment, and neuroma pain in a patient in need thereof comprising administration of a therapeutically effective amount of the composition according to  claim 19 . 
     
     
         44 . The method of  claim 43  wherein the disorder is selected from: chronic pain, osteoarthritis, peripheral neuropathy, acute pain due to fractures, musculoskeletal damage, pancreatitis and renal colic, pre-operative pain, peri-operative pain, post-operative pain, diabetic neuropathy, chronic lower back pain, pain resulting from chemotherapy, gouty arthritis, polymyalgia rheumatica, bone and joint pain, myofascial pain, muscular injury, fibromyalgia, shoulder tendonitis, and bursitis. 
     
     
         45 . The method of  claim 44  wherein the disorder is selected from: chronic pain, osteoarthritis, peripheral neuropathy, diabetic neuropathy, and chronic lower back pain.