Fused bicyclic oxazolidinone CETP inhibitor

1. A compound of Formula I,

or a pharmaceutically acceptable salt thereof,

wherein R 1 is H, —C 1 -C 5 alkyl, —OC 1 -C 5 alkyl, —C 2 -C 5 alkenyl, —OC 2 -C 5 alkenyl, —C 2 -C 5 alkynyl, —OC 2 -C 5 alkynyl, —OH, halogen, —CN, —NR 6 R 7 , —CO 2 R 8 , —C(O)NR 6 R 7 , —SO 2 NR 6 R 7 , HET(3), or C 3 - 6 cycloalkyl optionally having 1-2 double bonds, wherein —C 1 -C 5 alkyl, —OC 1 -C 5 alkyl, —C 2 -C 5 alkenyl, —OC 2 -C 5 alkenyl, —C 2 -C 5 alkynyl, and —OC 2 -C 5 alkynyl are each optionally substituted with 1-7 halogens, and wherein HET(3) and C 3 - 6 cycloalkyl optionally having 1-2 double bonds are optionally substituted with 1-3 substituent groups which are each independently halogen, —C 1 -C 3 alkyl, —OC 1 -C 3 alkyl, —C 2 -C 3 alkenyl, —OC 2 -C 3 alkenyl, —C 2 -C 3 alkynyl, or —OC 2 -C 3 alkynyl, wherein —C 1 -C 3 alkyl, —OC 1 -C 3 alkyl, —C 2 -C 3 alkenyl, —OC 2 -C 3 alkenyl, —C 2 -C 3 alkynyl, and —OC 2 -C 3 alkynyl are each optionally substituted with 1-7 halogens;

R 6 and R 7 are each independently H or —C 1 -C 5 alkyl;

R 8 is H or —C 1-5 alkyl optionally substituted with 1-7 halogens;

HET(3) is a 3-6 membered heterocyclic ring having 1-3 heteroatom groups which are each independently N, NH, O, S, S(O), or S(O) 2 and optionally having 1-3 double bonds;

x is 0 or 1;

The dashed lines in Formula I represent one optional double bond between 2 adjacent carbon atoms;

D 1 is N or CR 2 ;

D 2 is N or CR 3 ;

D 3 is N or CR 4 ;

R 2 , R 3 , and R 4 are each independently H, —C 1 -C 5 alkyl, —OC 1 -C 5 alkyl, —C 2 -C 5 alkenyl, —OC 2 -C 5 alkenyl, —C 2 -C 5 alkynyl, —OC 2 -C 5 alkynyl, —OH, halogen, —CN, —NR 6 R 7 , —CO 2 R 8 , —C(O) NR 6 R 7 , or —SO 2 NR 6 R 7 , wherein —C 1 -C 5 alkyl, —OC 1 -C 5 alkyl, —C 2 -C 5 alkenyl, —OC 2 -C 5 alkenyl, —C 2 -C 5 alkynyl, and —OC 2 -C 5 alkynyl are optionally substituted with 1-7 halogens;

Each R 5 is independently —C 1 -C 5 alkyl, —OC 1 -C 5 alkyl, —C 2 -C 5 alkenyl, —OC 2 -C 5 alkenyl, —C 2 -C 5 alkynyl, —OC 2 -C 5 alkynyl, —OH, halogen, —CN, —NR 6 R 7 , —CO 2 R 8 , —C(O) NR 6 R 7 , or —SO 2 NR 6 R 7 , wherein —C 1 -C 5 alkyl, —OC 1 -C 5 alkyl, —C 2 -C 5 alkenyl, —OC 2 -C 5 alkenyl, —C 2 -C 5 alkynyl, and —OC 2 -C 5 alkynyl are optionally substituted with 1-7 halogens;

A 1 is phenyl, HET(1), or C 3 -C 8 cycloalkyl optionally having 1-2 double bonds, wherein A 1 is optionally substituted with one substituent group Z and is optionally substituted with 1-3 groups which are each independently —C 1 -C 5 alkyl, —OC 1 -C 5 alkyl, —C 2 -C 5 alkenyl, —OC 2 -C 5 alkenyl, —C 2 -C 5 alkynyl, —OC 2 -C 5 alkynyl, halogen, —OH, or —CN, wherein —C 1 -C 5 alkyl, —OC 1 -C 5 alkyl, —C 2 -C 5 alkenyl, —OC 2 -C 5 alkenyl, —C 2 -C 5 alkynyl, and —OC 2 -C 5 alkynyl are optionally substituted with 1-7 halogens;

Each HET(1) is a 5- or 6-membered heterocyclic ring having 1-4 heteroatom groups which are each independently —N—, —NH—, —S—, —O—, —S(O)—,or —S(O) 2 —, optionally having one group —C(═O)—, and optionally having 1-3 double bonds;

Z is A 3 , —C 1 -C 3 alkylene-CO 2 R 8 , —C 1 -C 3 alkylene-C(O)NR 6 R 7 , —C 1 -C 3 alkylene-SO 2 NR 6 R 7 , —CO 2 R 8 , —C(O)NR 6 R 7 , —SO 2 NR 6 R 7 , or —C 1 -C 3 alkylene-HET(2), wherein —C 1 -C 3 alkylene in all uses is optionally substituted with 1-7 halogens, and HET(2) is optionally substituted with 1-3 substituents which are independently —C 1-3 alkyl optionally substituted with 1-5 halogens, —OC 1-3 alkyl optionally substituted with 1-5 halogens, halogen or NR 6 R 7 ;

A 3 is phenyl, C 3 -C 6 cycloalkyl optionally having 1-2 double bonds, or HET(1), wherein A 3 is optionally substituted with 1-3 groups which are each independently —C 1 -C 5 alkyl, —OC 1 -C 5 alkyl, —C 2 -C 5 alkenyl, —OC 2 -C 5 alkenyl, —C 2 -C 5 alkynyl, —OC 2 -C 5 alkynyl, halogen, —OH, or —CN, wherein —C 1 -C 5 alkyl, —OC 2 -C 5 alkyl, —C 2 -C 5 alkenyl, —OC 2 -C 5 alkenyl, —C 2 -C 5 alkynyl, and —OC 2 -C 5 alkynyl are optionally substituted with 1-7 halogens; and A 3 is optionally substituted with one group which is HET(2), —C 1 - 4 alkylene-CO 2 R 8 , —C 1 - 4 alkylene-C(O)NR 6 R 7 , —C 1 -C 4 alkylene-SO 2 NR 6 R 7 , —CO 2 R 8 , —C(O)NR 6 R 7 , or —SO 2 NR 6 R 7 , wherein —C 1 -C 4 alkylene in all uses is optionally substituted with 1-7 halogens; and wherein HET(2) is optionally substituted with 1-3 groups which are each independently halogen, —C 1- 5 alkyl optionally substituted with 1-7 halogens, —OC 1-5 alkyl optionally substituted with 1-7 halogens, or NR 6 R 7 ;

HET(2) is a 5-6 membered heterocyclic ring having 1-3 heteroatom groups which are each independently N, NH, O, or S, optionally having one group —C(═O)—, and optionally having 1-3 double bonds;

A 2 is phenyl or HET(1), wherein A 2 is optionally substituted with 1-3 substituent groups which are each independently —C 1 -C 5 alkyl, —OC 1 -C 5 alkyl, —C 2 -C 5 alkenyl, —OC 2 -C 5 alkenyl, —C 2 -C 5 alkynyl, —OC 2 -C 5 alkynyl, halogen, —CN, —OH, or C 3- 6 cycloalkyl, wherein —C 1 -C 5 alkyl, —OC 1 -C 5 alkyl, —C 2 -C 5 alkenyl, —OC 2 -C 5 alkenyl, —C 2 -C 5 alkynyl, and —OC 2 -C 5 alkynyl are optionally substituted with 1-7 halogens, and C 3-6 cycloalkyl is optionally substituted with 1-3 substituents which are each independently halogen, —C 1 -C 3 alkyl, or —OC 1 -C 3 alkyl, wherein —C 1 -C 3 alkyl and —OC 1 -C 3 alkyl are each optionally substituted with 1-7 halogens; and

a is 0 or an integer from 1-3.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof:

wherein R 1 is —C 1 -C 5 alkyl, —OC 1 -C 5 alkyl, halogen, —NR 6 R 7 , HET(3), or C 3-6 cycloalkyl optionally having 1-2 double bonds, wherein —C 1 -C 5 alkyl and —OC 1 -C 5 alkyl are optionally substituted with 1-7 halogens, and wherein HET(3) and C 3 - 6 cycloalkyl optionally having 1-2 double bonds are optionally substituted with 1-3 substituent groups which are each independently halogen, CH 3 , CF 3 , OCH 3 , or OCF 3 ;

At least one of D 1 , D 2 , or D 3 is CR 2 , CR 3 , or CR 4 ;

R 2 , R 3 , and R 4 are each independently H, —C 1 -C 5 alkyl, —OC 1 -C 5 alkyl, or halogen, wherein —C 1 -C 5 alkyl and —OC 1 -C 5 alkyl are optionally substituted with 1-7 halogens;

Each R 5 is independently —C 1 -C 5 alkyl, —OC 1 -C 5 alkyl, or halogen, wherein —C 1 -C 5 alkyl and —OC 1 -C 5 alkyl are optionally substituted with 1-7 halogens;

A 1 is phenyl, HET(1), or C 3 -C 6 cycloalkyl optionally having 1-2 double bonds, wherein A 1 is optionally substituted with one substituent group Z and is optionally substituted with 1-3 groups which are each independently halogen, —OH, —CN, —C 1 - 5 alkyl optionally substituted with 1-7 halogens, or —OC 1 - 5 alkyl optionally substituted with 1-7 halogens;

A 3 is phenyl, C 3 -C 6 cycloalkyl optionally having 1-2 double bonds, or HET(1), wherein A 3 is optionally substituted with 1-3 groups which are each independently —C 1 -C 5 alkyl optionally substituted with 1-7 halogens, —OC 1 -C 5 alkyl optionally substituted with 1-7 halogens, —OH, or halogen, and is optionally substituted with one group which is HET(2), —C 1 - 2 alkylene-CO 2 R 8 , —C 1-2 alkylene-C(O)NR 6 R 7 , —C 1 -C 2 alkylene-SO 2 NR 6 R 7 , —CO 2 R 8 , —C(O)NR 6 R 7 , or —SO 2 NR 6 R 7 , wherein —C 1 -C 2 alkylene is optionally substituted with 1-3 halogens; and wherein HET(2) is optionally substituted with 1-3 groups which are each independently halogen, —C 1 - 5 alkyl optionally substituted with 1-7 halogens, —OC 1-5 alkyl optionally substituted with 1-7 halogens, or NR 6 R 7 ; and

A 2 is phenyl or HET(1), wherein A 2 is optionally substituted with 1-3 substituent groups which are each independently C 1 - 5 alkyl optionally substituted with 1-7 halogens, —OC 1-5 alkyl optionally substituted with 1-7 halogens, halogen, —OH, —CN, or C 3-6 cycloalkyl optionally substituted with 1-3 substituents which are each independently halogen, CF 3 , CH 3 , —OCF 3 , or —OCH 3 .

3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof:

wherein R 1 is CH 3 , CF 3 , —OCH 3 , —OCF 3 , halogen, or —NR 6 R 7 ;

R 6 and R 7 are each independently H or —C 1 -C 3 alkyl;

R 2 , R 3 , and R 4 are each independently H, C 1-3 alkyl, CF 3 , —OC 1-3 alkyl, —OCF 3 , or halogen;

Each R 5 is independently CH 3 , CF 3 , —OCH 3 , —OCF 3 , or halogen;

A 1 is phenyl, HET(1), or C 3 -C 6 cycloalkyl optionally having 1-2 double bonds, wherein A 1 is optionally substituted with one substituent group Z and is optionally substituted with 1-3 groups which are each independently —C 1-3 alkyl optionally substituted with 1-5 halogens, —OC 1-3 alkyl optionally substituted with 1-5 halogens, halogen, —OH, or —CN;

Each HET(1) is a 5- or 6-membered heterocyclic ring having 1-3 heteroatom groups which are each independently —N—, —NH—, —S—, or —O—, optionally having one group —C(═O)—, and optionally having 1-3 double bonds;

Z is A 3 , —(CH 2 ) 1-3 —CO 2 R 8 , —(CH 2 ) 1-3 —C(O)NR 6 R 7 , —(CH 2 ) 1-3 —SO 2 NR 6 R 7 , —CO 2 R 8 , —C(O)NR 6 R 7 , —SO 2 NR 6 R 7 , or —(CH 2 ) 1-3 —HET(2), wherein HET(2) is optionally substituted with 1-3 substituents which are independently —C 1-3 alkyl optionally substituted with 1-5 halogens, —OC 1-3 alkyl optionally substituted with 1-5 halogens, halogen or NR 6 R 7 ;

R 8 is H or —C 1-3 alkyl optionally substituted with 1-3 halogens;

A 3 is phenyl, C 3 -C 6 cycloalkyl optionally having 1-2 double bonds, or HET(1), wherein A 3 is optionally substituted with 1-3 groups which are each independently CH3, CF3, —OCH 3 , —OCF 3 , —OH, or halogen, and is optionally substituted with one group which is HET(2), —(CH 2 ) 1-2 —CO 2 R 8 , —(CH 2 ) 1-2 —C(O)NR 6 R 7 , —(CH 2 ) 1-2 —SO 2 NR 6 R 7 , —CO 2 R 8 , —C(O) NR 6 R 7 , or —SO 2 NR 6 R 7 , and HET(2) is optionally substituted with 1-3 groups which are each independently CH 3 , CF 3 , —OCH 3 , —OCF 3 , halogen, or NR 6 R 7 ;

A 2 is phenyl or HET(1), wherein A 2 is substituted with 1-3 substituent groups which are each independently CH 3 , CF 3 , —OCH 3 , —OCF 3 , halogen, —CN, —OH, or C 3-4 cycloalkyl optionally substituted with 1-3 substituents which are each independently halogen, CF 3 , CH 3 , —OCF 3 , or —OCH 3 ; and

a is 0, 1, or 2.

4. The compound of claim 3 having Formula Ia,

or a pharmaceutically acceptable salt thereof,

wherein the dashed line in the ring in Formula Ia is an optional double bond.

5. The compound of claim 4 , or a pharmaceutically acceptable salt thereof:

wherein R 1 is CH 3 , CF 3 , —OCH 3 , —OCF 3 , F, Cl, or —NR 6 R 7 ;

D 1 is N or CR 2 , wherein R 2 is H, —C 1-3 alkyl, F, or Cl;

D 2 is N or CR 3 , wherein R 3 is H, —C 1-3 alkyl, F, or Cl;

D 3 is N or CR 4 , wherein R 4 is H, —C 1-3 alkyl, F, or Cl;

At least one of D 1 , D 2 , or D 3 is CR 2 , CR 3 , or CR 4 ;

R 5 is H or CH 3 ;

A 1 is phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxadiazolyl, thiadiazolyl, oxazolyl, pyrrolyl, thienyl, furyl, cyclopropyl, cyclobutyl, cyclohexyl, cyclohexenyl, cyclopentyl, or cyclopentenyl, wherein A 1 is optionally substituted with 1-3 groups which are each independently F, Cl, —OCH 3 , —OCF 3 , —C 1-3 alkyl, —CN, or CF 3 ,and optionally one substituent group Z;

Z is A 3 , —CH 2 CH 2 CO 2 R 8 , —CH 2 CH 2 C(O) NR 6 R 7 , —CH 2 CH 2 SO 2 NR 6 R 7 , or —CH 2 CH 2 —HET(2), wherein HET(2) is optionally substituted with 1-2 substituent groups which are each independently CH 3 , CF 3 , —OCH 3 , —OCF 3 , halogen, or NR 6 R 7 ;

R 8 is H or —CH 3 ;

HET(2) is a 5-membered heterocyclic ring having 1-3 heteroatom groups which are each independently N, NH, O, or S, optionally having one group —C(═O), and optionally having 1-3 double bonds;

A 3 is phenyl, cyclopropyl, cyclobutyl, cyclohexyl, cyclohexenyl, cyclopentyl, cyclopentenyl, or HET(1), wherein HET(1) is pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxadiazolyl, thiadiazolyl, oxazolyl, pyrrolyl, thienyl, furyl, or a 5-6-membered heterocyclic ring having 1-2 heteroatom groups which are independently —N—, —NH—or —O—, and optionally one —C(═O)— group, wherein A 3 is optionally substituted with 1-2 groups which are each independently CH 3 , CF 3 , —OCH 3 ; —OCF 3 , —OH, or halogen, and is optionally substituted with 1 group which is —CO 2 R 8 , —C(O) NR 6 R 7 , —SO 2 NR 6 R 7 , or HET(2), wherein HET(2) is optionally substituted with 1-2 substituent groups which are each independently CH 3 , CF 3 , —OCH 3 ; —OCF 3 , halogen, or NR 6 R 7 ;

A 2 is phenyl or HET(1) wherein A 2 is substituted with 1-3 substituent groups which are each independently CF 3 , CH 3 , F, Cl, —CN, or cyclopropyl; and

a is 0 or 1.

6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof:

wherein the dashed line in the ring in Formula Ia is an optionall double bond when x is 0;

wherein R 1 is CF 3 , F, or —N(CH 3 ) 2 ;

D 1 is N or CR 2 , wherein R 2 is H or C 1-3 alkyl;

D 2 is N or CR 3 , wherein R 3 is H or CH 3 ;

D 3 is N or CR 4 , wherein R 4 is H or CH 3 ;

A 1 is phenyl, pyridyl, thienyl, furyl, cyclohexenyl, or cyclopentenyl, wherein A 1 is optionally substituted with 1-3 groups which are each independently F, Cl, —OCH 3 , isopropyl, —CN, —CH 3 , or CF 3 , and optionally one substituent group Z;

Z is A 3 , —CH 2 CH 2 CO 2 R 8 , —CH 2 CH 2 -(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl), or —CH 2 CH 2 -(5-amino-1,3,4-oxadiazol-2-yl);

R 8 is H or —CH 3 ;

A 3 is phenyl, cyclobutyl, cyclopentyl, cyclohexyl, or HET(1), wherein HET(1) is pyridinyl, 6-oxopiperidinyl, 2-oxo-1,3-oxazolidinyl, 2-oxo-1,3-oxazinanyl, or 5-oxopyrrolidinyl, wherein A 3 is optionally substituted with 1-2 groups —CH 3 , —OCH 3 , or —OH, and is optionally substituted with 1 group -(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl), -(5-amino-1,3,4-oxadiazol-2-yl), or —CO 2 R 8 ;

A 2 is phenyl, which is substituted with 1-2 substituent groups which are each independently CF 3 , CH 3 , F, or Cl; and

a is 0.

7. The compound of claim 6 , having the structure below:

or a pharmaceutically acceptable salt thereof.

8. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1 or a phainiaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

9. A method of treating atherosclerosis in a patient in need of treatment comprising the administration of a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof to said patient.

10. A method of raising HDL-C in a patient in need of treatment comprising the administration of a therapeutically effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof to said patient.

11. A method of lowering LDL-C in a patient in need of treatment comprising the administration of a therapeutically effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof to said patient.

12. A method of treating dyslipidemia in a patient in need of treatment comprising the administration of a therapeuticallyeffective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof to said patient.

13. A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable carrier, and one or more active ingredients selected from the group consisting of:

(i) HMG-CoA reductase inhibitors;

(ii) bile acid sequestrants;

(iii) niacin and related compounds;

(iv) PPARα agonists;

(v) cholesterol absorption inhibitors;

(vi) acyl CoA:cholesterol acyltransferase (ACAT) inhibitors;

(vii) phenolic anti-oxidants;

(viii) microsomal triglyceride transfer protein (MTP)/ApoB secretion inhibitors;

(ix) anti-oxidant vitamins;

(x) thyromimetics;

(xi) LDL (low density lipoprotein) receptor inducers;

(xii) platelet aggregation inhibitors;

(xiii) vitamin B12 (also known as cyanocobalamin);

(xiv) folic acid or a pharmaceutically acceptable salt or ester thereof;

(xv) FXR and LXR ligands;

(xvi) agents that enhance ABCA1 gene expression;

(xvii) ileal bile acid transporters; and

(xviii) niacin receptor agonists.

14. A compound, or a pharmaceutically acceptable salt thereof, having the structure:

15. A compound, or a pharmaceutically acceptable salt thereof, having the structure:

16. A compound, or a pharmaceutically acceptable salt thereof, having the structure:

17. A compound, or a pharmaceutically acceptable salt thereof, having the structure:

18. A compound, or a pharmaceutically acceptable salt thereof, having the structure:

19. A compound having the structure:

20. A compound having the structure:

21. A compound having the structure:

22. A compound having the structure:

23. The compound having the structure:

24. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 14 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

25. A method of treating atherosclerosis in a patient in need of treatment comprising the administration of a therapeutically effective amount of the compound of claim 14 or a pharmaceutically acceptable salt thereof to said patient.

26. A method of raising HDL-C in a patient in need of treatment comprising the administration of a therapeutically effective amount of the compound of claim 14 or a pharmaceutically acceptable salt thereof to said patient.

27. A method of lowering LDL-C in a patient in need of treatment comprising the administration of a therapeutically effective amount of the compound of claim 14 or a pharmaceutically acceptable salt thereof to said patient.

28. A method of treating dyslipidemia in a patient in need of treatment comprising the administration of a therapeutically effective amount of the compound of claim 14 or a pharmaceutically acceptable salt thereof to said patient.

29. A pharmaceutical composition comprising the compound of claim 14 or a pharmaceutically acceptable salt thereof a pharmaceutically acceptable carrier, and an HMG-CoA reductase inhibitor, wherein the HMG-CoA reductase inhibitor is a statin or a pharmaceutically acceptable salt thereof.

30. The pharmaceutical composition of claim 29 wherein the statin is simvastatin, atorvastatin, or rosuvastatin, or a pharmaceutically acceptable salt thereof.

31. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 15 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

32. A method of treating atherosclerosis in a patient in need of treatment comprising the administration of a therapeutically effective amount of the compound of claim 15 or a pharmaceutically acceptable salt thereof to said patient.

33. A method of raising HDL-C in a patient in need of treatment comprising the administration of a therapeutically effective amount of the compound of claim 15 or a pharmaceutically acceptable salt thereof to said patient.

34. A method of lowering LDL-C in a patient in need of treatment comprising the administration of a therapeutically effective amount of the compound of claim 15 or a pharmaceutically acceptable salt thereof to said patient.

35. A method of treating dyslipidemia in a patient in need of treatment comprising the administration of a therapeutically effective amount of the compound of claim 15 or a pharmaceutically acceptable salt thereof to said patient.

36. A pharmaceutical composition comprising the compound of claim 15 or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable carrier, and an HMG-CoA reductase inhibitor, wherein the HMG-CoA reductase inhibitor is a statin or a pharmaceutically acceptable salt thereof.

37. The pharmaceutical composition of claim 36 wherein the statin is simvastatin, atorvastatin, or rosuvastatin, or a pharmaceutically acceptable salt thereof.

38. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 16 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

39. A method of treating atherosclerosis in a patient in need of treatment comprising the administration of a therapeutically effective amount of the compound of claim 16 or a pharmaceutically acceptable salt thereof to said patient.

40. A method of raising HDL-C in a patient in need of treatment comprising the administration of a therapeutically effective amount of the compound of claim 16 or a pharmaceutically acceptable salt thereof to said patient.

41. A method of lowering LDL-C in a patient in need of treatment comprising the administration of a therapeutically effective amount of the compound of claim 16 or a pharmaceutically acceptable salt thereof to said patient.

42. A method of treating dyslipidemia in a patient in need of treatment comprising the administration of a therapeutically effective amount of the compound of claim 16 or a pharmaceutically acceptable salt thereof to said patient.

43. A pharmaceutical composition comprising the compound of claim 16 or a pharmaceutically acceptable salt thereof a pharmaceutically acceptable carrier, and an HMG-CoA reductase inhibitor, wherein the HMG-CoA reductase inhibitor is a statin or a pharmaceutically acceptable salt thereof.

44. The pharmaceutical composition of claim 43 wherein the statin is simvastatin, atorvastatin, or rosuvastatin, or a pharmaceutically acceptable salt thereof.

45. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 17 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

46. A method of treating atherosclerosis in a patient in need of treatment comprising the administration of a therapeutically effective amount of the compound of claim 17 or a pharmaceutically acceptable salt thereof to said patient.

47. A method of raising HDL-C in a patient in need of treatment comprising the administration of a therapeutically effective amount of the compound of claim 17 or a pharmaceutically acceptable salt thereof to said patient.

48. A method of lowering LDL-C in a patient in need of treatment comprising the administration of a therapeutically effective amount of the compound of claim 17 or a pharmaceutically acceptable salt thereof to said patient.

49. A method of treating dyslipidemia in a patient in need of treatment comprising the administration of a therapeutically effective amount of the compound of claim 17 or a pharmaceutically acceptable salt thereof to said patient.

50. A pharmaceutical composition comprising the compound of claim 17 or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable carrier, and an HMG-CoA reductase inhibitor, wherein the HMG-CoA reductase inhibitor is a statin or a pharmaceutically acceptable salt thereof.

51. The pharmaceutical composition of claim 50 wherein the statin is simvastatin, atorvastatin, or rosuvastatin, or a pharmaceutically acceptable salt thereof.

52. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 18 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

53. A method of treating atherosclerosis in a patient in need of treatment comprising the administration of a therapeutically effective amount of the compound of claim 18 or a pharmaceutically acceptable salt thereof to said patient.

54. A method of raising HDL-C in a patient in need of treatment comprising the administration of a therapeutically effective amount of the compound of claim 18 or a pharmaceutically acceptable salt thereof to said patient.

55. A method of lowering LDL-C in a patient in need of treatment comprising the administration of a therapeutically effective amount of the compound of claim 18 or a pharmaceutically acceptable salt thereof to said patient.

56. A method of treating dyslipidemia in a patient in need of treatment comprising the administration of a therapeutically effective amount of the compound of claim 18 or a pharmaceutically acceptable salt thereof to said patient.

57. A pharmaceutical composition comprising the compound of claim 18 or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable carrier, and an HMG-CoA reductase inhibitor, wherein the HMG-CoA reductase inhibitor is a statin or a pharmaceutically acceptable salt thereof.

58. The pharmaceutical composition of claim 57 wherein the statin is simvastatin, atorvastatin, or rosuvastatin, or a pharmaceutically acceptable salt thereof.

59. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein HET(1) is a 5- or 6-membered heteroaromatic ring having 1-4 heteroatom groups which are each independently N, NH, S or O.

60. The compound of claim 5 , or a pharmaceutically acceptable salt thereof, wherein A 3 is phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, oxadiazolyl, thiadiazolyl, oxazolyl, pyrrolyl, thienyl, furyl, cyclopropyl, cyclobutyl, cyclohexyl, cyclohexenyl, cyclopentyl, or cyclopentenyl, wherein A 3 is optionally substituted with 1-2 groups which are each independently CH 3 , CF 3 , —OCH 3 , —OCF 3 , or halogen, and is optionally substituted with 1 group which is —CO 2 R 8 , —C(O)NR 6 R 7 , —SO 2 NR 6 R 7 , or HET(2), wherein HET(2) is optionally substituted with 1-2 substituent groups which are each independently CH 3 , CF 3 , —OCH 3 , —OCF 3 , halogen, or NR 6 R 7 .