ABCA1 elevating compounds

1. A compound having the structure of Formula I:

wherein:

R 1 is optionally substituted lower alkyl, optionally substituted cycloalkyl, or optionally substituted aryl;

R 2 is hydrogen, carboxyalkyl, optionally substituted lower alkyl, optionally substituted cycloalkyl, or optionally substituted aryl;

R 3 is optionally substituted aryl or optionally substituted heteroaryl;

R 4 , R 5 , and R 6 are independently hydrogen or optionally substituted lower alkyl with the proviso that R 5 and R 6 cannot both be lower alkyl; and

A is 5 or 6 membered monocyclic cycloalkyl or monocyclic aryl ring.

2. The compound of claim 1 , wherein A is trans cyclohexyl.

3. The compound of claim 2 , wherein R 4 , R 5 , and R 6 are hydrogen or methyl.

4. The compound of claim 3 , wherein R 3 is optionally substituted aryl.

5. The compound of claim 4 , wherein R 2 is hydrogen, optionally substituted C 1-4 alkyl, carboxy, or C 1-4 carboxyalkyl.

6. The compound of claim 5 , wherein R 1 is hydrogen or optionally substituted lower alkyl.

7. The compound of claim 6 , wherein R 1 is optionally substituted benzyl or ethylphenyl.

8. The compound of claim 7 , selected from the group consisting of:

N-[(4-methylphenyl)methyl][4-({[(2-methylphenyl)methyl](phenylsulfonyl)amino}methyl)cyclohexyl]carboxamide;

N-[(4-methylphenyl)methyl]{4-[((phenylsulfonyl) {[3-(trifluoromethyl)phenyl]methyl}amino)methyl]cyclohexyl}carboxamide;

N-[(4-methylphenyl)methyl]{4-[((phenylsulfonyl) {[4-(trifluoromethyl)phenyl]methyl}amino)methyl]cyclohexyl}carboxamide;

[4-({[(2-chlorophenyl)methyl](phenylsulfonyl)amino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(2,3-difluorophenyl)methyl](phenylsulfonyl)amino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(2-methoxyphenyl)methyl](phenylsulfonyl)amino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

N-[(4-methylphenyl)methyl][4-({[(4-phenylphenyl)methyl](phenylsulfonyl)amino}methyl)cyclohexyl]carboxamide;

[4-({[(4-fluorophenyl)methyl](phenylsulfonyl)amino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(3,4-difluorophenyl)methyl](phenylsulfonyl)amino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(3-methoxyphenyl)methyl](phenylsulfonyl)amino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(4-methoxyphenyl)methyl](phenylsulfonyl)amino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(3-fluorophenyl)methyl](phenylsulfonyl)amino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(2-fluorophenyl)methyl](phenylsulfonyl)amino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

methyl 4-({[4-({[(4-phenylphenyl)methyl](phenylsulfonyl)amino}methyl)cyclohexyl]carbonyl amino}methyl)benzoate;

[4-({[(3-methoxyphenyl)methyl](phenylsulfonyl)amino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

N-[(4-methylphenyl)methyl][4-({[(3-methylphenyl)methyl](phenylsulfonyl)amino}methyl)cyclohexyl]carboxa mide;

{4-[({[2-chloro-3-(trifluoromethyl)phenyl]methyl}(phenylsulfonyl)amino)methyl]cyclohexyl}-N-[(4-methylphenyl)methyl]carboxamide;

N-[(4-methylphenyl)methyl](4-{[benzyl(phenylsulfonyl)amino]methyl}cyclohexyl)carboxamide;

methyl 4-{[(4-{[benzyl(phenylsulfonyl)amino]methyl}cyclohexyl)carbonylamino]methyl}benzoate;

methyl 4-({[4-({[(2-methylphenyl)methyl](phenylsulfonyl)amino}methyl)cyclohexyl]carbonyl amino}methyl)benzoate;

N-[(4-methylphenyl)methyl](4-{[(phenylethyl)(phenylsulfonyl)amino]methyl}cyclohexyl)carboxamide; 4-{[(4-{[benzyl(phenylsulfonyl)amino]methyl}cyclohexyl)carbonylamino]methyl}benzoic acid;

N-[(4-methylphenyl)methyl](4-{[(2-phenylethyl)(phenylsulfonyl)amino]methyl}cyclohexyl)carboxamide;

(4-{[((1R)-1-phenylethyl)(phenylsulfonyl)amino]methyl}cyclohexyl)-N-[(4-methylphenyl)methyl]carboxamide;

(4-{[((1S)-1-phenylethyl)(phenylsulfonyl)amino]methyl}cyclohexyl)-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(3-methoxyphenyl)sulfonyl]benzylamino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

N-[4-({[(4-{N-[(4-methylphenyl)methyl]carbamoyl}cyclohexyl)methyl]benzylamino}sulfonyl)phenyl]acetamide;

N-[(4-methylphenyl)methyl][4-({[(2-methylphenyl)sulfonyl]benzylamino}methyl)cyclohexyl]carboxamide;

[4-({[(2,4-difluorophenyl)sulfonyl]benzylamino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(4-chloro-2-fluorophenyl)sulfonyl]benzylamino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(3,4-difluorophenyl)sulfonyl]benzylamino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

{4-[({[4-(tert-butyl)phenyl]sulfonyl}benzylamino)methyl]cyclohexyl}-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(2,4-dichlorophenyl)sulfonyl]benzylamino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

N-[(4-methylphenyl)methyl][4-({benzyl[(2,3,4-trifluorophenyl)sulfonyl]amino}methyl)cyclohexyl]carboxamide;

[4-({[(3,5-difluorophenyl)sulfonyl]benzylamino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(3,4-dimethoxyphenyl)sulfonyl]benzylamino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(2,5-difluorophenyl)sulfonyl]benzylamino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(3-chlorophenyl)sulfonyl]benzylamino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(2-fluorophenyl)sulfonyl]benzylamino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(2-chlorophenyl)sulfonyl]benzylamino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(3,5-dimethylphenyl)sulfonyl]benzylamino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

{4-[({[3,5-bis(trifluoromethyl)phenyl]sulfonyl}benzylamino)methyl]cyclohexyl}-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(3-chloro-4-methylphenyl)sulfonyl]benzylamino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(5-fluoro-2-methylphenyl)sulfonyl]benzylamino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(2,5-dichlorophenyl)sulfonyl]benzylamino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

{4-[({[4-(methylethyl)phenyl]sulfonyl}benzylamino)methyl]cyclohexyl}-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(2,6-difluorophenyl)sulfonyl]benzylamino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(3-fluorophenyl)sulfonyl]benzylamino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(3,5-dichlorophenyl)sulfonyl]benzylamino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(4-fluoro-2-methylphenyl)sulfonyl]benzylamino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

N-[(4-methylphenyl)methyl][4-({benzyl[(2,4,6-trimethylphenyl)sulfonyl]amino}methyl)cyclohexyl]carboxamide;

N-[(4-methylphenyl)methyl]{4-[(benzyl {[2-(trifluoromethyl)phenyl]sulfonyl}amino)methyl]cyclohexyl}carboxamide;

N-[(4-methylphenyl)methyl]{4-[(benzyl {[3-(trifluoromethyl)phenyl]sulfonyl}amino)methyl]cyclohexyl}carboxamide;

N-[(4-methylphenyl)methyl][4-({[(2,3,4,5,6-pentafluorophenyl)sulfonyl]benzylamino}methyl)cyclohexyl]carboxamide;

N-[(4-methylphenyl)methyl](4-{[(naphthylsulfonyl)benzylamino]methyl}cyclohexyl)carboxamide;

[4-({[(3-fluoro-4-methylphenyl)sulfonyl]benzylamino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(3-chloro-4-fluorophenyl)sulfonyl]benzylamino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

N-[(4-methylphenyl)methyl](4-{[(2-naphthylsulfonyl)benzylamino]methyl}cyclohexyl)carboxamide;

[4-({[(3,4-dichlorophenyl)sulfonyl]benzylamino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

N-[(4-methylphenyl)methyl][4-({[(4-methylphenyl)sulfonyl]benzylamino}methyl)cyclohexyl]carboxamide;

[4-({[(4-chlorophenyl)sulfonyl]benzylamino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(4-methoxyphenyl)sulfonyl]benzylamino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(3-chloro-2-fluorophenyl)sulfonyl]benzylamino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

N-[(4-methylphenyl)methyl][4-({benzyl[(4-phenylphenyl)sulfonyl]amino}methyl)cyclohexyl]carboxamide;

[4-({[(2,6-dimethylphenyl)methyl](phenylsulfonyl)amino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

N-[(4-methylphenyl)methyl]{4-[((phenylsulfonyl) {[2-(trifluoromethyl)phenyl]methyl}amino)methyl]cyclohexyl}carboxamide;

N-[(4-methylphenyl)methyl]{4-[((phenylsulfonyl) {[2-(trifluoromethyl)phenyl]ethyl}amino)methyl]cyclohexyl}carboxamide;

N-methyl-N-benzyl(4-{[benzyl(phenylsulfonyl)amino]methyl}cyclohexyl)carboxamide;

(4-{[benzyl(phenylsulfonyl)amino]methyl}cyclohexyl)-N-{[4-(trifluoromethyl)phenyl]methyl}carboxamide;

[4-({[(4-fluorophenyl)methyl](phenylsulfonyl)amino}methyl)cyclohexyl]-N-{[4-(trifluoromethyl)phenyl]methyl}carboxamide;

[4-({[(4-fluorophenyl)methyl](phenylsulfonyl)amino}methyl)cyclohexyl]-N-methyl-N-benzylcarboxamide;

{4-[([(4-fluorophenyl)methyl]{[2-(trifluoromethyl)phenyl]sulfonyl}amino)methyl]cyclohexyl}-N-[(4-methylphenyl)methyl]carboxamide;

{4-[([(2,3-difluorophenyl)methyl]{[2-(trifluoromethyl)phenyl]sulfonyl}amino)methyl]cyclohexyl}-N-[(4-methylphenyl)methyl]carboxamide;

N,N-bisbenzyl(4-{[(phenylsulfonyl)amino]methyl}cyclohexyl)carboxamide;

N-[(1S)-1-(4-methylphenyl)ethyl](4-{[benzyl(phenylsulfonyl)amino]methyl}cyclohexyl)carboxamide;

N-[(1S)-1-(4-methylphenyl)ethyl][4-({[(2-chlorophenyl)methyl](phenylsulfonyl)amino}methyl)cyclohexyl]carboxa mide;

N-[(1R)-1-(4-methylphenyl)ethyl](4-{[benzyl(phenylsulfonyl)amino]methyl}cyclohexyl)carboxamide;

N-[(1R)-1-(4-methylphenyl)ethyl][4-({[(2-chlorophenyl)methyl](phenylsulfonyl)amino}methyl)cyclohexyl]carboxa mide;

(4-{[((1R)-1-phenylethyl)(phenylsulfonyl)amino]methyl}cyclohexyl)-N-[(1S)-1-(4-methylphenyl)ethyl]carboxamide;

[4-({[(2,6-difluorophenyl)methyl](phenylsulfonyl)amino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

[4-({[(2,5-difluorophenyl)methyl](phenylsulfonyl)amino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide; and

[4-({[(3,5-difluorophenyl)methyl](phenylsulfonyl)amino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide.

9. The compound of claim 6 , wherein R 1 is hydrogen.

10. The compound of claim 9 , selected from the group consisting of:

N-[(4-methylphenyl)methyl](4-{[(phenylsulfonyl)amino]methyl}cyclohexyl)carboxamide;

methyl 4-{[(4-{[(phenylsulfonyl)amino]methyl}cyclohexyl) carbonylamino]methyl}benzoate;

N-{[4-(1-hydroxy-isopropyl)phenyl]methyl}(4-{[(phenylsulfonyl)amino]methyl}cyclohexyl)carboxamide; and

4-{[(4-{[(phenylsulfonyl)amino]methyl}cyclohexyl)carbonylamino]methyl}benzoic acid.

11. The compound of claim 6 , selected from the group consisting of:

(4-{[(cyclohexylmethyl)(phenylsulfonyl)amino]methyl}cyclohexyl)-N-[(4-methylphenyl)methyl]carboxamide;

N-[(4-methylphenyl)methyl](4-{[(2-methylpropyl)(phenylsulfonyl)amino]methyl}cyclohexyl)carboxamide; and

N-[(4-methylphenyl)methyl](4-{[(phenylsulfonyl)(2,2,2-trifluoroethyl)amino]methyl}cyclohexyl)carboxamide.

12. The compound of claim 6 , wherein R 1 is heteroaryl substituted alkyl.

13. The compound of claim 12 , selected from the group consisting of:

[4-({[(3,5-dimethylisoxazol-4-yl)methyl](phenylsulfonyl)amino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide;

N-[(4-methylphenyl)methyl](4-{[(phenylsulfonyl)(3-pyridylethyl)amino]methyl}cyclohexyl)carboxamide;

N-[(4-methylphenyl)methyl](4-{[(phenylsulfonyl)(3-pyridylmethyl)amino]methyl}cyclohexyl)carboxamide;

N-[(4-methylphenyl)methyl](4-{[(phenylsulfonyl)(4-pyridylmethyl)amino]methyl}cyclohexyl)carboxamide;

N-[(4-methylphenyl)methyl](4-{[(phenylsulfonyl)(2-pyridylmethyl)amino]methyl}cyclohexyl)carboxamide

[4-({[(5-methylisoxazol-3-yl)methyl](phenylsulfonyl)amino}methyl)cyclohexyl]-N-[(4-methylphenyl)methyl]carboxamide; and

N-[(4-methylphenyl)methyl][4-({[(5-phenyl(1,3,4-oxadiazol-2-yl))methyl](phenylsulfonyl)amino}methyl)cyclohexyl]carboxamide.

14. The compound of claim 5 , wherein R 1 is cycloalkyl.

15. The compound of claim 6 , wherein R 1 is selected from the group consisting of:

(4-{[((1R)(1,2,3,4-tetrahydronaphthyl))(phenylsulfonyl)amino]methyl}cyclohexyl)-N-[(4-methylphenyl)methyl]carboxamide; and

(4-{[((1S)(1,2,3,4-tetrahydronaphthyl))(phenylsulfonyl)amino]methyl}cyclohexyl)-N-[(4-methylphenyl)methyl]carboxamide.

16. The compound of claim 3 , wherein R 3 is optionally substituted heteroaryl, R 2 is methyl, and R 1 is benzyl.

17. The compound of claim 16 , selected from the group consisting of:

N-[4-methyl-5-({[(4-{N-[(4-methylphenyl)methyl]carbamoyl}cyclohexyl)methyl]benzylamino}sulfonyl)-1,3-thiazol-2-yl]acetamide; and

N-[(4-methylphenyl)methyl][4-({benzyl[(1,3,5-trimethylpyrazol-4-yl)sulfonyl]amino}methyl)cyclohexyl]carboxamide.

18. The compound of claim 1 , wherein A is phenyl, R 1 is benzyl, R 2 is methyl, R 3 is optionally substituted heteroaryl, and R 4 , R 5 , and R 6 are hydrogen.

19. The compound of claim 16 , selected from the group consisting of:

N-[(4-methylphenyl)methyl](4-{[benzyl(phenylsulfonyl)amino]methyl}phenyl)carboxamide; and

[4-({[(4-fluorophenyl)methyl](phenylsulfonyl)amino}methyl)phenyl]-N-[(4-methylphenyl)methyl]carboxamide.

20. A method of treating a disease state or condition in a mammal that is alleviable by treatment with an agent capable of increasing ABCA-1 expression, comprising administering to a mammal in need thereof a therapeutically effective dose of a compound of claim 1 , wherein the disease state or condition is coronary artery disease, atherosclerosis, dyslipidiemia or metabolic syndrome.

21. The method of claim 20 , wherein the disease state or condition is coronary artery disease or atherosclerosis.

22. A method for elevating serum levels of HDL cholesterol in a mammal, comprising administering to a mammal in need thereof a therapeutically effective dose of a compound of claim 1 .

23. A method for promoting cholesterol efflux from cells in a mammal, comprising administering to a mammal in need thereof a therapeutically effective dose of a compound of claim 1 .

24. A pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and a therapeutically effective amount of a compound of claim 1 .