LXR modulators

1. A compound, isotope, or pharmaceutically acceptable salt thereof, selected from the group consisting of:

No.

Name

1

2-(1-(3′-fluoro-4′-(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-4-yl)-

2-(2-(2-fluorophenyl)propan-2-yl)-1H-imidazol-4-yl)propan-2-ol;

2

2-(2-(2-(2-chloro-6-fluorophenyl)propan-2-yl)-1-(3′-fluoro-4′-

(hydroxymethyl)-3-methyl-5′-(methylsulfonyl)biphenyl-4-yl)-1H-

imidazol-4-yl)propan-2-ol;

3

2-(1-(3-chloro-3′-fluoro-4′-(hydroxymethyl)-5′-(methylsulfonyl)bi-

phenyl-4-yl)-2-(2-(2,6-dichlorophenyl)propan-2-yl)-1H-imidazol-4-

yl)propan-2-ol;

4

2-(2-(2-(2-chloro-3-fluorophenyl)propan-2-yl)-1-(3′-fluoro-4′-

(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-

yl)propan-2-ol;

5

2-(2-(2-(2,6-dichlorophenyl)propan-2-yl)-1-(3′-fluoro-4′-(hydroxy-

methyl)-5′-(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-yl)propan-

2-ol;

6

2-(2-(2-(2-Chloro-phenyl)propan-2-yl)-1-(3,3′-difluoro-4′-hydroxy-

methyl-5′-(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-yl)-propan-

2-ol;

7

2-(2-(2-(2-chloro-6-fluorophenyl)propan-2-yl)-1-(3,3′-difluoro-4′-

(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-

yl)propan-2-ol;

8

2-{1-(3,3′-Difluoro-4′-hydroxymethyl-5′-methanesulfonyl-biphenyl-

4-yl)-2-[2-(2-fluorophenyl)propan-2-yl]-1H-imidazol-4-yl}-propan-

2-ol;

9

2-(2-(2-(2,6-dichlorophenyl)propan-2-yl)-1-(3,3′-difluoro-4′-

(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-

4-yl)propan-2-ol;

10

2-(2-(2-(2,6-dichlorophenyl)propan-2-yl)-1-(3,3′-difluoro-4′-

(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-

yl)[( 13 CD 3 ) 2 ]propan-2-ol;

11

2-(2-(2,4-dichlorobenzyl)-1-(3,3′-difluoro-4′-(hydroxymethyl)-5′-

(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-yl)propan-2-ol;

12

2-(1-(3,3′-difluoro-4′-(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-

4-yl)-2-(2-(trifluoromethyl)benzyl)-1H-imidazol-4-yl)propan-2-ol;

13

2-(1-(3-chloro-3′-fluoro-4′-(hydroxymethyl)-5′-(methylsulfonyl)bi-

phenyl-4-yl)-2-(2-chloro-4-fluorobenzyl)-1H-imidazol-4-yl)propan-

2-ol;

14

2-(2-(2-chloro-4-fluorobenzyl)-1-(3,3′-difluoro-4′-(hydroxymethyl)-

5′-(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-yl)propan-2-ol;

15

2-(2-(2,4-dichlorobenzyl)-1-(3′-fluoro-4′-(hydroxymethyl)-5′-

(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-yl)propan-2-ol;

16

2-(1-(3,3′-difluoro-4′-(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-

4-yl)-2-(2-fluorobenzyl)-1H-imidazol-4-yl)propan-2-ol;

17

2-(1-(3′-fluoro-4′-(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-4-

yl)-2-(2-methylbenzyl)-1H-imidazol-4-yl)propan-2-ol;

18

2-(2-(2,6-dichlorobenzyl)-1-(3′-fluoro-4′-(hydroxymethyl)-5′-

(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-yl)propan-2-ol;

19

2-[2-(2-Chloro-5-fluoro-benzyl)-1-(3′-fluoro-4′-hydroxymethyl-5′-

methanesulfonyl-biphenyl-4-yl)-1H-imidazol-4-yl]-propan-2-ol;

20

2-[2-(2-Chloro-benzyl)-1-(3,3′-difluoro-4′-hydroxymethyl-5′-

methanesulfonyl-biphenyl-4-yl)-1H-imidazol-4-yl]-propan-2-ol;

[[or]] and

21

2-{2-[1-(2,6-dichlorophenyl)ethyl]-1-[3,3′-difluoro-4′-(hydroxy-

methyl)-5′-(methylsulfonyl)biphenyl-4-yl]-1H-imidazol-4-yl}propan-

2-ol.

2. The compound, isotope, or pharmaceutically acceptable salt thereof, of claim 1 selected from the group consisting of:

No.

Name

1

2-(1-(3′-fluoro-4′-(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-4-yl)-

2-(2-(2-fluorophenyl)propan-2-yl)-1H-imidazol-4-yl)propan-2-ol;

2

2-(2-(2-(2-chloro-6-fluorophenyl)propan-2-yl)-1-(3′-fluoro-4′-

(hydroxymethyl)-3-methyl-5′-(methylsulfonyl)biphenyl-4-yl)-1H-

imidazol-4-yl)propan-2-ol;

3

2-(1-(3-chloro-3′-fluoro-4′-(hydroxymethyl)-5′-(methylsulfonyl)bi-

phenyl-4-yl)-2-(2-(2,6-dichlorophenyl)propan-2-yl)-1H-imidazol-4-

yl)propan-2-ol;

4

2-(2-(2-(2-chloro-3-fluorophenyl)propan-2-yl)-1-(3′-fluoro-4′-

(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-

yl)propan-2-ol;

5

2-(2-(2-(2,6-dichlorophenyl)propan-2-yl)-1-(3′-fluoro-4′-(hydroxy-

methyl)-5′-(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-yl)propan-

2-ol;

6

2-(2-(2-(2-Chloro-phenyl)propan-2-yl)-1-(3,3′-difluoro-4′-hydroxy-

methyl-5′-(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-yl)-propan-

2-ol;

7

2-(2-(2-(2-chloro-6-fluorophenyl)propan-2-yl)-1-(3,3′-difluoro-4′-

(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-

yl)propan-2-ol;

8

2-{1-(3,3′-Difluoro-4′-hydroxymethyl-5′-methanesulfonyl-biphenyl-

4-yl)-2-[2-(2-fluorophenyl)propan-2-yl]-1H-imidazol-4-y1}-propan-

2-ol;

9

2-(2-(2-(2,6-dichlorophenyl)propan-2-yl)-1-(3,3′-difluoro-4′-

(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-

yl)propan-2-ol;

10

2-(2-(2-(2,6-dichlorophenyl)propan-2-yl)-1-(3,3′-difluoro-4′-

(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-

yl)[( 13 CD 3 ) 2 ]propan-2-ol; [[or]] and

21

2-{2-[1-(2,6-dichlorophenyl)ethyl]-1-[3,3′-difluoro-4′-(hydroxy-

methyl)-5′-(methylsulfonyl)biphenyl-4-yl]-1H-imidazol-4-yl}propan-

2-ol.

3. The compound, isotope, or pharmaceutically acceptable salt thereof, of claim 1 selected from the group consisting of:

No.

Name

11

2-(2-(2,4-dichlorobenzyl)-1-(3,3′-difluoro-4′-(hydroxymethyl)-5′-

(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-yl)propan-2-ol;

12

2-(1-(3,3′-difluoro-4′-(hydroxymethyl)-5′-(methylsulfonyl)bi-

phenyl-4-yl)-2-(2-(trifluoromethyl)benzyl)-1H-imidazol-4-yl)propan-

2-ol;

13

2-(1-(3-chloro-3′-fluoro-4′-(hydroxymethyl)-5′-(methylsulfonyl)bi-

phenyl-4-yl)-2-(2-chloro-4-fluorobenzyl)-1H-imidazol-4-yl)propan-

2-ol;

14

2-(2-(2-chloro-4-fluorobenzyl)-1-(3,3′-difluoro-4′-(hydroxy-

methyl)-5′-(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-yl)propan-

2-ol;

15

2-(2-(2,4-dichlorobenzyl)-1-(3′-fluoro-4′-(hydroxymethyl)-5′-

(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-yl)propan-2-ol;

16

2-(1-(3,3′-difluoro-4′-(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-

4-yl)-2-(2-fluorobenzyl)-1H-imidazol-4-yl)propan-2-ol;

17

2-(1-(3′-fluoro-4′-(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-4-

yl)-2-(2-methylbenzyl)-1H-imidazol-4-yl)propan-2-ol;

18

2-(2-(2,6-dichlorobenzyl)-1-(3′-fluoro-4′-(hydroxymethyl)-5′-

(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-yl)propan-2-ol;

19

2-[2-(2-Chloro-5-fluoro-benzyl)-1-(3′-fluoro-4′-hydroxymethyl-5′-

methanesulfonyl-biphenyl-4-yl)-1H-imidazol-4-yl]-propan-2-ol;

[[or]] and

20

2-[2-(2-Chloro-benzyl)-1-(3,3′-difluoro-4′-hydroxymethyl-5′-

methanesulfonyl-biphenyl-4-yl)-1H-imidazol-4-yl]-propan-2-ol.

4. The compound, isotope, or pharmaceutically acceptable salt thereof, of claim 1 selected from the group consisting of:

No.

Name

3

2-(1-(3-chloro-3′-fluoro-4′-(hydroxymethyl)-5′-(methylsulfonyl)bi-

phenyl-4-yl)-2-(2-(2,6-dichlorophenyl)propan-2-yl)-1H-imidazol-4-

yl)propan-2-ol;

4

2-(2-(2-(2-chloro-3-fluorophenyl)propan-2-yl)-1-(3′-fluoro-4′-

(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-

yl)propan-2-ol;

5

2-(2-(2-(2,6-dichlorophenyl)propan-2-yl)-1-(3′-fluoro-4′-(hydroxy-

methyl)-5′-(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-yl)propan-

2-ol;

9

2-(2-(2-(2,6-dichlorophenyl)propan-2-yl)-1-(3,3′-difluoro-4′-

(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-

yl)propan-2-ol;

10

2-(2-(2-(2,6-dichlorophenyl)propan-2-yl)-1-(3,3′-difluoro-4′-

(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-

yl)[( 13 CD 3 ) 2 ]propan-2-ol; [[or]] and

21

2-{2-[1-(2,6-dichlorophenyl)ethyl]-1-[3,3′-difluoro-4′-(hydroxy-

methyl)-5′-(methylsulfonyl)biphenyl-4-yl]-1H-imidazol-4-yl}propan-

2-ol.

5. A compound, isotope, or pharmaceutically acceptable salt thereof, which is 2-(1-(3-chloro-3′-fluoro-4′-(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-4-yl)-2-(2-(2,6-dichlorophenyl)propan-2-yl)-1H-imidazol-4-yl)propan-2-ol.

6. The compound, isotope, or pharmaceutically acceptable salt thereof of claim 4 , which is 2-(2-(2-(2-chloro-3-fluorophenyl)propan-2-yl)-1-(3′-fluoro-4′-(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-yl)propan-2-ol.

7. The compound, isotope, or pharmaceutically acceptable salt thereof of claim 4 , which is 2-(2-(2-(2,6-dichlorophenyl)propan-2-yl)-1-(3′-fluoro-4′-(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-yl)propan-2-ol.

8. A compound, isotope, or pharmaceutically acceptable salt thereof, which is 2-(2-(2-(2,6-dichlorophenyl)propan-2-yl)-1-(3,3′-difluoro-4′-(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-4-yl)-1H-imidazol-4-yl)propan-2-ol.

9. The compound, isotope, or pharmaceutically acceptable salt thereof of claim 4 , which is 2-{2-[1-(2,6-dichlorophenyl)ethyl]-1-[3,3′-difluoro-4′-(hydroxymethyl)-5′-(methylsulfonyl)biphenyl-4-yl]-1H-imidazol-4-yl}propan-2-ol.

10. A pharmaceutical composition comprising a compound, isotope, or pharmaceutically acceptable salt thereof of any one of claims 1 to 9 and one or more pharmaceutically acceptable carriers.

11. A method of treating a disease or disorder comprising administering to a subject in need thereof a therapeutically effective amount of a compound, isotope, or pharmaceutically acceptable salt thereof of claim 1 , wherein the disease or disorder is atherosclerosis, insulin resistance, osteoarthritis, stroke, hyperglycemia, dyslipidemia, psoriasis, age and UV exposure-related skin wrinkling, diabetes, cancer, Alzheimer's disease, inflammation, immunological disorders, lipid disorders, obesity, macular degeneration, conditions characterized by a perturbed epidermal barrier function, conditions of disturbed differentiation or excess proliferation of the epidermis or mucous membrane, or cardiovascular disorders.

12. The method of claim 11 wherein the disease or disorder is atherosclerosis, diabetes, Alzheimer's disease or dyslipidemia.

13. The method of claim 11 wherein the disease or disorder is atherosclerosis.

14. The method of claim 11 wherein the disease or disorder is diabetes.

15. The method of claim 11 wherein the disease or disorder is Alzheimer's disease.

16. A pharmaceutical composition comprising a compound, isotope, or pharmaceutically acceptable salt thereof of claim 4 and one or more pharmaceutically acceptable carriers.

17. A method of treating a disease or disorder comprising administering to a subject in need thereof a therapeutically effective amount of a compound, isotope, or pharmaceutically acceptable salt thereof of claim 4 , wherein the disease or disorder is atherosclerosis, insulin resistance, osteoarthritis, stroke, hyperglycemia, dyslipidemia, psoriasis, age and UV exposure-related skin wrinkling, diabetes, cancer, Alzheimer's disease, inflammation, immunological disorders, lipid disorders, obesity, macular degeneration, conditions characterized by a perturbed epidermal barrier function, conditions of disturbed differentiation or excess proliferation of the epidermis or mucous membrane, or cardiovascular disorders.

18. The method of claim 17 wherein the disease or disorder is atherosclerosis, diabetes, Alzheimer's disease or dyslipidemia.

19. A pharmaceutical composition comprising a compound, isotope, or pharmaceutically acceptable salt thereof of claim 5 and one or more pharmaceutically acceptable carriers.

20. A method of treating a disease or disorder comprising administering to a subject in need thereof a therapeutically effective amount of a compound, isotope, or pharmaceutically acceptable salt thereof of claim 5 , wherein the disease or disorder is atherosclerosis, insulin resistance, osteoarthritis, stroke, hyperglycemia, dyslipidemia, psoriasis, age and UV exposure-related skin wrinkling, diabetes, cancer, Alzheimer's disease, inflammation, immunological disorders, lipid disorders, obesity, macular degeneration, conditions characterized by a perturbed epidermal barrier function, conditions of disturbed differentiation or excess proliferation of the epidermis or mucous membrane, or cardiovascular disorders.

21. The method of claim 20 wherein the disease or disorder is atherosclerosis, diabetes, Alzheimer's disease or dyslipidemia.

22. The method of claim 20 wherein the disease or disorder is atherosclerosis.

23. The method of claim 20 wherein the disease or disorder is diabetes.

24. The method of claim 20 wherein the disease or disorder is Alzheimer's disease.

25. A pharmaceutical composition comprising a compound, isotope, or pharmaceutically acceptable salt thereof of claim 8 and one or more pharmaceutically acceptable carriers.

26. A method of treating a disease or disorder comprising administering to a subject in need thereof a therapeutically effective amount of a compound, isotope, or pharmaceutically acceptable salt thereof of claim 8 , wherein the disease or disorder is atherosclerosis, insulin resistance, osteoarthritis, stroke, hyperglycemia, dyslipidemia, psoriasis, age and UV exposure-related skin wrinkling, diabetes, cancer, Alzheimer's disease, inflammation, immunological disorders, lipid disorders, obesity, macular degeneration, conditions characterized by a perturbed epidermal barrier function, conditions of disturbed differentiation or excess proliferation of the epidermis or mucous membrane, or cardiovascular disorders.

27. The method of claim 26 wherein the disease or disorder is atherosclerosis, diabetes, Alzheimer's disease or dyslipidemia.

28. The method of claim 26 wherein the disease or disorder is atherosclerosis.

29. The method of claim 26 wherein the disease or disorder is diabetes.

30. The method of claim 26 wherein the disease or disorder is Alzheimer's disease.