IP Library › Granted Patent US 8,969,325

Granted Patent B2

US 8,969,325 · App. 13/716,862 · Granted Mar 3, 2015

TRPV1 antagonists

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Patent No.: US 8,969,325
App. No.: 13/716,862
Granted: Mar 3, 2015
Kind: B2

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Abstract

Disclosed herein are compounds of formula (I): or pharmaceutically acceptable salts thereof, wherein X 1 , L, R x , R y , G, Z, A, m, n, and p are as defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also disclosed.

Claims (387)

1. A compound of formula (I-f):

or a salt thereof, wherein:

G is formula (i), (ii), or (iii):

R a is hydrogen or methyl;

Y 1 is CH 2 and Y 2 is O; or

Y 1 is CR 1a R 1b , and Y 2 is CH 2 ; wherein R 1a is hydrogen, and R 1b is hydrogen or NR 1c R 1d wherein R 1c is hydrogen or methyl, and R 1d is —(C 1 -C 2 alkylenyl)-OH or —(C 1 -C 2 alkylenyl)-O(methyl), or R 1c and R 1d , together with the nitrogen atom to which they are attached form a monocyclic ring selected from the group consisting of morpholinyl and oxazepanyl; or

Y 1 is NR 1 and Y 2 is CH 2 ; wherein R 1 is hydrogen, methyl, or —(C 1 -C 2 alkylenyl)-OH;

R c is hydrogen, methyl, or ethyl;

Y 3 is CR 3a R 3b , and Y 4 is O; wherein R 3a and R 3b are each independently hydrogen or methyl; or

Y 3 and Y 4 are CH 2 ; or

Y 3 is NR 3 and Y 4 is CH 2 ; wherein R 3 is hydrogen or methyl;

R d is hydrogen or methyl;

R b , at each occurrence, represents an optional substituent on the benzo moiety of the bicyclic rings of formula (i), (ii), and (iii), and is independently alkyl, halogen, or haloalkyl

q is 0;

Z is O or S;

A is CH or N;

L is a bond or CH 2 ;

m is 0, 1, 2, 3, or 4;

R x , at each occurrence, represents an optional substituent on any substitutable carbon atom of the ring containing A, and each R x is independently C 1-6 -alkyl, halogen, halomethyl, OH, O(methyl), or O(halomethyl);

p is 0, 1, or 2; and

R y , at each occurrence, represents an optional substituent on any substitutable carbon atom of the ring containing O, and each R y is independently C 1-6 -alkyl, halomethyl, or —CH 2 -O(methyl);

two R y groups that are attached to the same carbon atom, together with said carbon atom to which they are attached, optionally form an unsubstituted cyclobutyl or cyclopentyl ring.

2. The compound or salt according to claim 1 , wherein A is CH, Z is O, and L is a bond.

3. The compound or salt according to claim 1 , wherein A is CH, Z is S, and L is a bond.

4. The compound or salt according to claim 1 , wherein A is N, Z is O, and L is a bond.

5. The compound or salt according to claim 1 , wherein A is CH, Z is O, and L is CH 2 .

6. The compound or salt according to claim 1 , wherein

G is formula (i).

7. The compound or salt according to claim 1 , wherein

G is formula (ii).

8. The compound or salt according to claim 1 , wherein

G is formula (iii).

9. The compound or salt according to claim 1 , wherein A is CH.

10. The compound or salt according to claim 1 , wherein A is N.

11. The compound or salt according to claim 1 , wherein A is CH and Z is O.

12. The compound or salt according to claim 1 , wherein A is N and Z is O.

13. The compound or salt according to claim 1 , wherein:

G is formula (i);

A is CH;

L is a bond; and

Z is O.

14. The compound or salt according to claim 13 , wherein:

R a is hydrogen,

Y 1 is CH 2 , and

Y 2 is O.

15. The compound or salt according to claim 13 , wherein:

R a is hydrogen or methyl,

Y 1 is cR 1a R 1b ,

R 1a is hydrogen,

R 1b is hydrogen, and

Y 2 is CH 2 .

16. The compound or salt according to claim 1 , wherein:

G is formula (ii);

A is CH;

L is a bond; and

Z is O.

17. The compound or salt according to claim 1 , wherein:

G is formula (iii);

A is CH;

L is a bond; and

Z is O.

18. The compound or salt according to claim 1 , wherein:

G is formula (i);

A is N;

L is a bond; and

Z is O.

19. The compound or salt according to claim 1 , wherein:

G is formula (i);

A is CH;

L is a bond; and

Z is S.

20. The compound or salt according to claim 1 , wherein the compound is selected from the group consisting of:

1-[(4R)-7-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-7-chloro-8-fluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-7-chloro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(2S,4R)-2-(difluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-3,4-dihydrospiro[chromene-2,1′-cyclopentan]-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-2,2-dimethyl-8-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)-3-[(2R,4R)-2-methyl-2-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;

1-[(4R)-6-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)-3-[(2S,4R)-2-methyl-2-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;

1-[(2S,4R)-2-(difluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(2R,4R)-2-(difluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-7-chloro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(2R,4R)-7-chloro-2-(difluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-7-chloro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-2,2-dimethyl-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-7,8-difluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(2R,4R)-2-methyl-2-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)-3-[(4R)-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;

1-[(4R)-7-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea; and

1-[(4R)-7-chloro-8-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea.

21. The compound or salt according to claim 1 , wherein the compound is selected from the group consisting of:

1-[(4R)-7-chloro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-8-chloro-7-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(2R,4R)-7-chloro-2-(fluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-ethyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(2R,4R)-7-chloro-2-(difluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(2S,4R)-7-chloro-2-(difluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(2R,4R)-2-(difluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(2S,4R)-7-chloro-2-(fluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-7-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-7-chloro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-7-chloro-8-fluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-8-chloro-7-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-7-chloro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-7-fluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(2R,4R)-7-chloro-2-(fluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(2S,4R)-7-chloro-2-(fluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-8-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(4R)-7-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(4R)-2,2-diethyl-8-fluoro-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(4R)-2,2-diethyl-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(4R)-2,2-diethyl-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(4R)-7-chloro-2,2-diethyl-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(4R)-2,2-dimethyl-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(4R)-6-fluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(4R)-2,2-diethyl-6-fluoro-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(4R)-6-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(4R)-6-fluoro-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]-3-[(4R)-8-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;

1-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]-3-[(4R)-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;

1-[(4S)-6-fluoro-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(4S)-6-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(2S,4R)-2-(fluoromethyl)-2-methyl-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(2S,4R)-7-chloro-2-(fluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(2R,4R)-2-(difluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(4R)-7-chloro-8-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(4R)-7-bromo-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)-3-[(4R)-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;

1-[(4R)-3,4-dihydrospiro[chromene-2,1′-cyclopentan]-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-2,2-diethyl-8-fluoro-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-2,2-diethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-2,2-diethyl-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-7-chloro-2,2-diethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-6-fluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-6,8-difluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-6-fluoro-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-2,2-diethyl-6-fluoro-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-8-fluoro-2,2-dipropyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-2,2-diethyl-7-(trifluoromethoxy)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)-3-[(4S)-7-(trifluoromethoxy)-3,4-dihydro-2H-chromen-4-yl]urea;

1-[(4R)-6-fluoro-2,2-bis(methoxymethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-7,8-difluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-6-fluoro-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(2S,4R)-2-(fluoromethyl)-2-methyl-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-7-chloro-8-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)-3-[(4R)-7-(trifluoromethoxy)-3,4-dihydro-2H-chromen-4-yl]urea;

1-[(4S)-6-fluoro-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-7-bromo-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)-3-[(2R,4R)-2-methyl-2-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;

1-[(4R)-2,2-dimethyl-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-2,2-bis(fluoromethyl)-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-2,2-dimethyl-8-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-8-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-8-fluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)-3-[(4R)-8-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;

1-[(4S)-6-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-7-chloro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2-dihydroquinolin-5-yl)urea;

1-[(4R)-8-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(4R)-2,2-diethyl-8-fluoro-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(4R)-2,2-diethyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(4R)-2,2-diethyl-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(4R)-7-chloro-2,2-diethyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(4R)-7,8-dichloro-2,2-diethyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(4R)-2,2-dimethyl-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(4R)-6-fluoro-2,2-dipropyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(4R)-6-fluoro-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(4R)-2,2-diethyl-6-fluoro-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(4R)-8-fluoro-2,2-dipropyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(4R)-2,2-diethyl-7-(trifluoromethoxy)-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(4R)-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(4R)-6-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(4R)-7-chloro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)-3-[(4R)-7-(trifluoromethoxy)-3,4-dihydro-2H-chromen-4-yl]urea;

1-[(4R)-8-fluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(4R)-7,8-difluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(4R)-6-fluoro-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)-3-[(4R)-8-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;

1-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)-3-[(4R)-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;

1-[(4S)-6-fluoro-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(4S)-6-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(4R)-3,4-dihydrospiro[chromene-2,1′-cyclopentan]-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(2S,4R)-2-methyl-2-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(2R,4R)-2-methyl-2-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(2S,4R)-2-(fluoromethyl)-2-methyl-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(2R,4R)-2-(fluoromethyl)-2-methyl-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(2S,4R)-7-chloro-2-(fluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(2S,4R)-2-(difluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(2R,4R)-2-(difluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(4R)-7-chloro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-[(2R)-2-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-8-yl]urea;

1-[(4R)-8-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-7-chloro-2-(difluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-2,2-dimethyl-7-(trifluoromethoxy)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)-3-[(4R)-8-(trifluoromethoxy)-3,4-dihydro-2H-chromen-4-yl]urea;

1-[(4R)-2,2-diethyl-8-fluoro-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-2,2-diethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-8-tert-butyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-2,2-diethyl-7-fluoro-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-2,2-diethyl-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-7-chloro-2,2-diethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-2,2-bis(fluoromethyl)-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-7,8-dichloro-2,2-diethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-8-chloro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-2,2-bis(fluoromethyl)-7-(trifluoromethoxy)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-2,2-dimethyl-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-6-fluoro-2,2-dipropyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-6-fluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-6,8-difluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-6-fluoro-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-2,2-diethyl-6-fluoro-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-8-fluoro-2,2-dipropyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-6-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-7-fluoro-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)-3-[(4R)-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;

1-[(4R)-7-chloro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-ethyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(2R,4R)-2-(fluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(2S,4R)-2-(fluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)-3-[(2S,4R)-2-methyl-2-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;

1-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)-3-[(2R,4R)-2-methyl-2-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;

1-[(4R)-7-chloro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1,3-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-[(4R)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea;

1-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)-3-[(4S)-7-(trifluoromethoxy)-3,4-dihydro-2H-chromen-4-yl]urea;

1-[(4R)-7-chloro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(2S,4R)-2-(difluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-8-chloro-7-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-2,2-bis(fluoromethyl)-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-7-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-2,2-diethyl-8-fluoro-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-2,2-diethyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-2,2-diethyl-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-7-chloro-2,2-diethyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-7,8-dichloro-2,2-diethyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-2,2-bis(fluoromethyl)-7-(trifluoromethoxy)-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-2,2-dimethyl-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-6-fluoro-2,2-dipropyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-6-fluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-6,8-difluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-6-fluoro-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-2,2-diethyl-6-fluoro-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-8-fluoro-2,2-dipropyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-2,2-diethyl-7-(trifluoromethoxy)-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-7-chloro-8-fluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)-3-[(4S)-7-(trifluoromethoxy)-3,4-dihydro-2H-chromen-4-yl]urea;

1-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)-3-[(4R)-7-(trifluoromethoxy)-3,4-dihydro-2H-chromen-4-yl]urea;

1-[(4R)-6-fluoro-2,2-bis(methoxymethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-8-fluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-6-fluoro-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)-3-[(4R)-8-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;

1-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)-3-[(4R)-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;

1-[(4S)-6-fluoro-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4S)-6-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-3,4-dihydrospiro[chromene-2,1′-cyclopentan]-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(2R,4R)-2-(fluoromethyl)-2-methyl-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(2R,4R)-2-(difluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-7-fluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-8-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl)urea;

1-[(4R)-2,2-bis(fluoromethyl)-7-(trifluoromethoxy)-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(2S,4R)-7-chloro-2-(difluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-6-fluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-6,8-difluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-8-fluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4S)-7-chloro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-2,2-dimethyl-8-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-8-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-7-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-2,2-diethyl-8-fluoro-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-2,2-diethyl-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-2,2-diethyl-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-7-chloro-2,2-diethyl-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-7,8-dichloro-2,2-diethyl-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-6-fluoro-2,2-dipropyl-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-6-fluoro-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-2,2-diethyl-6-fluoro-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-8-fluoro-2,2-dipropyl-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-7-chloro-8-fluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-6-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-8-chloro-7-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)-3-[(4S)-7-(trifluoromethoxy)-3,4-dihydro-2H-chromen-4-yl]urea;

1-[(4R)-7-chloro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)-3-[(4R)-7-(trifluoromethoxy)-3,4-dihydro-2H-chromen-4-yl]urea;

1-[(4R)-6-fluoro-2,2-bis(methoxymethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)-3-[(4R)-8-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;

1-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)-3-[(4R)-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;

1-[(2R,4R)-7-chloro-2-(fluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4S)-6-fluoro-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4S)-6-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-3,4-dihydrospiro[chromene-2,1′-cyclopentan]-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(2S,4R)-2-methyl-2-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(2S,4R)-7-chloro-2-(fluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(2S,4R)-2-(difluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(2R,4R)-2-(difluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-7-fluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-7-chloro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)thiourea;

1-[(4R)-7-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-7-chloro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-5-yl)urea;

1-[(4R)-7-chloro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-2,2-dimethyl-8-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-8-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-2,2-diethyl-8-fluoro-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-2,2-diethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-2,2-diethyl-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-7-chloro-2,2-diethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-2,2-bis(fluoromethyl)-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-7,8-dichloro-2,2-diethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-2,2-dimethyl-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-6-fluoro-2,2-dipropyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-6-fluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-6,8-difluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-6-fluoro-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-2,2-diethyl-6-fluoro-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-8-fluoro-2,2-dipropyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-2,2-diethyl-7-(trifluoromethoxy)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-7-chloro-8-fluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-6-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-8-chloro-7-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)-3-[(4S)-7-(trifluoromethoxy)-3,4-dihydro-2H-chromen-4-yl]urea;

1-[(4R)-7-chloro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)-3-[(4R)-7-(trifluoromethoxy)-3,4-dihydro-2H-chromen-4-yl]urea;

1-[(4R)-6-fluoro-2,2-bis(methoxymethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-8-fluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-6-fluoro-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)-3-[(4R)-8-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;

1-[(4S)-6-fluoro-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4S)-6-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-3,4-dihydrospiro[chromene-2,1′-cyclopentan]-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(2S,4R)-2-(fluoromethyl)-2-methyl-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(2R,4R)-2-(fluoromethyl)-2-methyl-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(2S,4R)-7-chloro-2-(fluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(2S,4R)-2-(difluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(2R,4R)-2-(difluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-7-chloro-8-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-7-fluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-7-bromo-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)-3-[(2S,4R)-2-methyl-2-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea;

1-[(4R)-7,8-difluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(4R)-7-chloro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-[3-(morpholin-4-yl)-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl]urea;

1-[(4R)-7-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-[3-(morpholin-4-yl)-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl]urea;

1-[(4R)-7-chloro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-[3-(1,4-oxazepan-4-yl)-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl]urea;

1-[(4R)-7-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-[3-(1,4-oxazepan-4-yl)-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl]urea;

1-[(4R)-7-chloro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-{3-[(2-hydroxyethyl)(methyl)amino]-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl}urea;

1-[(4R)-7-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-{3-[(2-methoxyethyl)(methyl)amino]-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl}urea;

1-[(4R)-7-chloro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-{3-[(2-methoxyethyl)(methyl)amino]-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl}urea;

1-[(4R)-2,2-dimethyl-8-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(4R)-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(4R)-2,2-bis(fluoromethyl)-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(4R)-6-fluoro-2,2-dipropyl-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(4R)-8-fluoro-2,2-dipropyl-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(4R)-8-chloro-7-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(4R)-7-chloro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(4R)-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(4R)-8-fluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(4R)-7-chloro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(4R)-3,4-dihydrospiro[chromene-2,1′-cyclopentan]-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(2S,4R)-2-(difluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(4R)-7-fluoro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-[3-(2-hydroxyethyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]urea;

1-[(4R)-2,2-bis(fluoromethyl)-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)urea;

1-[(2R,4R)-7-chloro-2-(difluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(2S,4R)-7-chloro-2-(difluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(4R)-7-chloro-2,2-bis(fluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-8-yl)urea;

1-[(4R)-2,2-bis(fluoromethyl)-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-[(4R)-7-chloro-8-fluoro-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)urea;

1-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)-3-[(2R,4R)-2-methyl-2-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl]urea; and

1-[(2S,4R)-7-chloro-2-(difluoromethyl)-2-methyl-3,4-dihydro-2H-chromen-4-yl]-3-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-5-yl)urea.

22. The compound of claim 1 , or a salt thereof, wherein the compound when administered to a human subject produces an increase in average time for hand withdrawal from a temperature-controlled water bath relative to a vehicle control that is less than about 30 seconds.

23. The compound of claim 1 , or a salt thereof, wherein the compound when tested in a rat tail immersion model of noxious thermosensation produces a percent increase in average response latency for tail withdrawal relative to a vehicle control that is less than about 20%.

24. The compound of claim 1 , or a salt thereof, wherein the compound when contacted in vitro at a concentration of 10 μM with human TRPV1 receptor blocks intracellular calcium flux relative to intracellular calcium flux measured in vitro for human TRPV1 receptor at a pH of about 5.0 in the absence of such compound by less than about 75%.

25. The compound of claim 1 , or a salt thereof, wherein the compound:

(a) when tested in a rat tail immersion model of noxious thermosensation produces a percent increase in average response latency for tail withdrawal relative to a vehicle control that is less than about 20%; and

(b) when contacted in vitro at a concentration of 10 μM with human TRPV1 receptor blocks intracellular calcium flux relative to intracellular calcium flux measured in vitro for human TRPV1 receptor at a pH of about 5.0 in the absence of such compound by less than about 75%.

26. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I-f) according to claim 1 , or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier.

27. The pharmaceutical composition according to claim 26 further comprising an analgesic or a nonsteroidal anti-inflammatory drug, or a combination thereof.

28. A method for treating pain comprising administering a therapeutically effective amount of a compound of formula (I-f) according to claim 1 , or a pharmaceutically acceptable salt thereof, to a subject in need thereof.

29. The method according to claim 28 further comprising the step of co-administering with an analgesic or a nonsteroidal anti-inflammatory drug, or a combination thereof.

30. The method according to claim 29 wherein the nonsteroidal anti-inflammatory drug is ibuprofen.

31. A method for treating an inflammatory state selected from the group consisting of burns, rheumatoid arthritis, and osteoarthritis, the method comprising administering a therapeutically effective amount of a compound of formula (I-f) according to claim 1 , or a pharmaceutically acceptable salt thereof, to a subject in need thereof.

Assignments (1)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 5, 2014

From: DART, MICHAEL J.; KYM, PHILIP R.; VOIGHT, ERIC A.; SHRESTHA, ANURUPA; DANNEN, JEROME F.; JINKERSON, TAMMIE K.; KEDDY, RYAN G.; PEDDI, SRIDHAR; GOMTSYAN, ARTHUR; KORT, MICHAEL E.; GFESSER, GREGORY A.; WOLLER, KEVIN R.; NELSON, DEREK W.

To: ABBVIE INC.

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