2-oxoimidazolidine-4-carboxamides as NA
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 compound of structural Formula I:
or a pharmaceutically acceptable salt thereof, wherein
A is selected from:
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:
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:
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:
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:
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:
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:
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:
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:
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:
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 can be 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 can be 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 can be 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 can be 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; and
q is independently selected from 0 to 3.
2. The compound according to claim 1 wherein A is phenyl unsubstituted or substituted with one to five substituents selected from R a ; or a pharmaceutically acceptable salt thereof.
3. The compound according to claim 1 wherein B is selected from:
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.
4. The compound according to claim 1 wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are each hydrogen; or a pharmaceutically acceptable salt thereof.
5. The compound according to claim 1 wherein each R a is independently selected from:
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.
6. The compound according to claim 1 wherein each R a is independently selected from:
1) —CF 3 ,
2) —OCF 3 , and
3) halogen;
or a pharmaceutically acceptable salt thereof.
7. The compound according to claim 1 wherein each R b is independently selected from:
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.
8. The compound according to claim 1 wherein each R b is independently selected from:
(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.
9. The compound according to claim 1 wherein
A is selected from:
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:
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:
(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:
(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:
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:
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:
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:
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;
each R b is independently selected from:
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.
10. The compound according to claim 1 wherein
A is phenyl unsubstituted or substituted with one to five substituents selected from R a ;
B is selected from:
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:
1) —CF 3 ,
2) —OCF 3 , and
3) halogen;
each R b is independently selected from:
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.
11. The compound according to claim 1 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-((ci s)-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)-13-methyl)-2-oxoimidazolidine-4-carboxamide;
86) (S)—N—((S)-(3-chloro-4-(trifluoromethoxy)phenyl)(1-(trifluoromethyl)-1H-pyrazol-4-yl)-13-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)((ci s)-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)((ci s)-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)((ci s)-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;
or a pharmaceutically acceptable salt thereof.
12. A compound selected from:
1) (S)—N—((R)-(5-fluoro-6-(trifluoromethyl)pyridin-2-yl)(4-(trifluoromethoxy)-phenyl)-methyl)-2-oxoimidazolidine-4-carboxamide;
2) (S)—N—((S)-(5-fluoro-6-(trifluoromethyl)pyridin-2-yl)(4-(trifluoromethoxy)-phenyl)-methyl)-2-oxoimidazolidine-4-carboxamide;
3) (S)—N—((R)-(3-chlorophenyl)(4-(trifluoromethoxy)phenyl)methyl)-2-oxoimidazolidine-4-carboxamide;
4) (S)—N—((S)-(3-chlorophenyl)(4-(trifluoromethoxy)phenyl)methyl)-2-oxoimidazolidine-4-carboxamide;
5) (S)—N—((R)-(3-chloro-2,4-difluorophenyl)(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide;
6) (S)—N—((S)-(3-chloro-2,4-difluorophenyl)(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)methyl)-2-oxoimidazolidine-4-carboxamide;
7) (S)—N—((R)-(3-chloro-2,4-difluorophenyl)(trans-3-(trifluoromethyl)cyclobutyl)-methyl)-2-oxoimidazolidine-4-carboxamide; and
8) (S)—N—((S)-(3-chloro-2,4-difluorophenyl)(trans-3-(trifluoromethyl)cyclobutyl)-methyl)-2-oxoimidazolidine-4-carboxamide;
or a pharmaceutically acceptable salts thereof.
13. A composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
14. A method of treating a disorder selected from: a pain disorder, a cough disorder, an acute itch disorder or a chronic itch disorder in a patient in need thereof comprising administration of a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof.
15. The method of claim 14 wherein the disorder is a pain disorder.
16. The method of claim 15 wherein the pain disorder is selected from: acute pain, inflammatory pain, and neuropathic pain.
17. The compound according to claim 12 which is: (S)—N—((R)-(3-chlorophenyl)(4-(trifluoromethoxy)phenyl)methyl)-2-oxoimidazolidine-4-carboxamide; or a pharmaceutically acceptable salt thereof.
18. The compound according to claim 12 which is: (S)—N—((S)-(3-chlorophenyl)(4-(trifluoromethoxy)phenyl)methyl)-2-oxoimidazolidine-4-carboxamide; or a pharmaceutically acceptable salt thereof.
19. The compound according to claim 12 which is: (S)—N—((R)-(5-fluoro-6-(trifluoromethyl)pyridin-2-yl)(4-(trifluoromethoxy)phenyl)methyl)-2-oxoimidazolidine-4-carboxamide; or a pharmaceutically acceptable salt thereof.
20. The compound according to claim 12 which is: (S)—N—((S)-(5-fluoro-6-(trifluoromethyl)pyridin-2-yl)(4-(trifluoromethoxy)phenyl)methyl)-2-oxoimidazolidine-4-carboxamide; or a pharmaceutically acceptable salt thereof.
21. The compound according to claim 12 which is: (S)—N—((R)-(3-chloro-2,4-difluorophenyl)(trans-3-(trifluoromethyl)cyclobutyl)-methyl)-2-oxoimidazolidine-4-carboxamide; or a pharmaceutically acceptable salt thereof.
22. The compound according to claim 12 which is: (S)—N—((S)-(3-chloro-2,4-difluorophenyl)(trans-3-(trifluoromethyl)cyclobutyl)-methyl)-2-oxoimidazolidine-4-carboxamide; or a pharmaceutically acceptable salt thereof.
23. 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, erythromyelalgia, paroxysmal extreme pain disorder, small fiber neuropathy, repetitive motion pain, dental pain, myofascial pain, muscular injury, fibromyalgia, chronic pain, dysmennorhea, pain associated with angina, shoulder tendonitis, bursitis, gouty arthritis, aolymyalgia 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 a compound according to claim 1 .
24. The method of claim 23 wherein the disorder is selected from: 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, bone and joint pain, myofascial pain, muscular injury, fibromyalgia, shoulder tendonitis, and bursitis.
25. The method of claim 23 wherein the disorder is chronic pain.
26. The compound according to claim 12 which is: (S)-N-((R)-(3-chlorophenyl)(4-(trifluoromethoxy)phenyl)methyl)-2-oxoimidazolidine-4-carboxamide.
27. A composition comprising a compound of claim 26 , and a pharmaceutically acceptable carrier.
28. A method of treating a disorder selected from: 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, bone and joint pain, myofascial pain, muscular injury, fibromyalgia, shoulder tendonitis, and bursitis in a patient in need thereof comprising administration of a therapeutically effective amount of a compound according to claim 26 .
29. The compound according to claim 12 which is: (S)-N-((S)-(3-chlorophenyl)(4-(trifluoromethoxy)phenyl)methyl)-2-oxoimidazolidine-4-carboxamide.
30. A composition comprising a compound of claim 29 , and a pharmaceutically acceptable carrier.
31. A method of treating a disorder selected from: 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, bone and joint pain, myofascial pain, muscular injury, fibromyalgia, shoulder tendonitis, and bursitis in a patient in need thereof comprising administration of a therapeutically effective amount of a compound according to claim 29 .
32. The compound according to claim 12 which is: (S)-N4R)-(5-fluoro-6-(trifluoromethyl)pyridin-2-yl)(4-(trifluoromethoxy)phenyl)methyl)-2-oxoimidazolidine-4-carboxamide.
33. A composition comprising a compound of claim 32 , and a pharmaceutically acceptable carrier.
34. A method of treating a disorder selected from: 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, bone and joint pain, myofascial pain, muscular injury, fibromyalgia, shoulder tendonitis, and bursitis in a patient in need thereof comprising administration of a therapeutically effective amount of a compound according to claim 32 .
35. The compound according to claim 12 which is: (S)-N-((S)-(5-fluoro-6-(trifluoromethyl)pyridin-2-yl)(4-(trifluoromethoxy)phenyl)methyl)-2-oxoimidazolidine-4-carboxamide.
36. A composition comprising a compound of claim 35 , and a pharmaceutically acceptable carrier.
37. A method of treating a disorder selected from: 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, bone and joint pain, myofascial pain, muscular injury, fibromyalgia, shoulder tendonitis, and bursitis in a patient in need thereof comprising administration of a therapeutically effective amount of a compound according to claim 35 .
38. The compound according to claim 12 which is: (S)-N-((R)-(3-chloro-2,4-difluorophenyl)(trans-3-(trifluoromethyl)cyclobutyl)-methyl)-2-oxoimidazolidine-4-carboxamide.
39. A composition comprising a compound of claim 38 , and a pharmaceutically acceptable carrier.
40. A method of treating a disorder selected from: 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, bone and joint pain, myofascial pain, muscular injury, fibromyalgia, shoulder tendonitis, and bursitis in a patient in need thereof comprising administration of a therapeutically effective amount of a compound according to claim 38 .
41. The compound according to claim 12 which is: (S)-N-((S)-(3-chloro-2,4-difluorophenyl)(trans-3-(trifluoromethyl)cyclobutyl)-methyl)-2-oxoimidazolidine-4-carboxamide.
42. A composition comprising a compound of claim 41 , and a pharmaceutically acceptable carrier.
43. A method of treating a disorder selected from: 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, bone and joint pain, myofascial pain, muscular injury, fibromyalgia, shoulder tendonitis, and bursitis in a patient in need thereof comprising administration of a therapeutically effective amount of a compound according to claim 41 .
44. 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, erythromyelalgia, paroxysmal extreme pain disorder, small fiber neuropathy, repetitive motion pain, dental pain, myofascial pain, muscular injury, fibromyalgia, chronic pain, dysmennorhea, pain associated with angina, shoulder tendonitis, bursitis, gouty arthritis, aolymyalgia 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 a compound according to claim 12 .
45. The method of claim 44 wherein the disorder is selected from:
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, bone and joint pain, myofascial pain, muscular injury, fibromyalgia, shoulder tendonitis, and bursitis.
46. The method of claim 44 wherein the disorder is chronic pain.