CETP inhibitors

1. A compound having Formula I, or a pharmaceutically acceptable salt thereof, wherein

Y is selected from the group consisting of —C(═O)— and —(CRR 1 )—;

X is selected from the group consisting of —O—, —NH—, —N(C 1 -C 5 alkyl)-, and —(CRR 6 )—;

Z is selected from the group consisting of —C(═O)—, —S(O) 2 —, and —C(═N—R 9 )—, wherein R 9 is selected from the group consisting of H, —CN, and C 1 -C 5 alkyl optionally substituted with 1-11 halogens;

Each R is independently selected from the group consisting of H, —C 1 -C 5 alkyl, and halogen, wherein —C 1 -C 5 alkyl is optionally substituted with 1-11 halogens;

B is selected from the group consisting of A 1 and A 2 , wherein A 1 has the structure:

R 1 and R 6 are each selected from the group consisting of H, —C 1 -C 5 alkyl, halogen, and —(C(R) 2 ) n A 2 , wherein —C 1 -C 5 alkyl is optionally substituted with 1-11 halogens;

R 2 is selected from the group consisting of H, —C 1 -C 5 alkyl, halogen, A 1 , and —(C(R) 2 ) n A 2 , wherein —C 1 -C 5 alkyl is optionally substituted with 1-11 halogens;

Wherein one of B and R 2 is A 1 ; and one of B, R 1 , R 2 , and R 6 is A 2 or —(C(R) 2 ) n A 2 ; so that the compound of Formula I comprises one group A 1 and one group A 2 ;

A 3 is selected from the group consisting of:

(a) an aromatic ring selected from phenyl and naphthyl;

(b) a phenyl ring fused to a 5-7 membered non-aromatic cycloalkyl ring, which optionally comprises 1-2 double bonds;

(c) a 5-6-membered heterocyclic ring having 1-4 heteroatoms independently selected from N, S, O, and —N(O)—, and optionally also comprising 1-3 double bonds and a carbonyl group, wherein the point of attachment of A 3 to the phenyl ring to which A 3 is attached is a carbon atom; and

(d) a benzoheterocyclic ring comprising a phenyl ring fused to a 5-6-membered heterocyclic ring having 1-2 heteroatoms independently selected from O, N, and —S(O) x — and optionally 1-2 double bonds, wherein the point of attachment of A 3 to the phenyl ring to which A 3 is attached is a carbon atom;

A 2 is selected from the group consisting of:

(a) an aromatic ring selected from phenyl and naphthyl;

(b) a phenyl ring fused to a 5-7 membered non-aromatic cycloalkyl ring, which optionally comprises 1-2 double bonds;

(c) a 5-6-membered heterocyclic ring having 1-4 heteroatoms independently selected from N, S, O, and —N(O)—, and optionally also comprising 1-3 double bonds and a carbonyl group;

(d) a benzoheterocyclic ring comprising a phenyl ring fused to a 5-6-membered heterocyclic ring having 1-2 heteroatoms independently selected from O, N, and S and optionally 1-2 double bonds; and

(e) a —C 3 -C 8 cycloalkyl ring optionally having 1-3 double bonds;

wherein A 3 and A 2 are each optionally substituted with 1-5 substituent groups independently selected from R a ;

Each R a is independently selected from the group consisting of —C 1 -C 6 alkyl, —C 2 -C 6 alkenyl, —C 2 -C 6 alkynyl, —C 3 -C 8 cycloalkyl optionally having 1-3 double bonds, —OC 1 -C 6 alkyl, —OC 2 -C 6 alkenyl, —OC 2 -C 6 alkynyl, —OC 3 -C 8 cycloalkyl optionally having 1-3 double bonds, —C(═O)C 1 -C 6 alkyl, —C(═O)C 3 -C 8 cycloalkyl, —C(═O)H, —CO 2 H, —CO 2 C 1 -C 6 alkyl, —C(═O)SC 1 -C 6 alkyl, —OH, —NR 3 R 4 , —C(═O)NR 3 R 4 , —NR 3 C(═O)OC 1 -C 6 alkyl, —NR 3 C(═O)NR 3 R 4 , —S(O) x C 1 -C 6 alkyl, —S(O) y NR 3 R 4 , —NR 3 S(O) y NR 3 R 4 , halogen, —CN, —NO 2 , and a 5-6-membered heterocyclic ring having 1-4 heteroatoms independently selected from N, S, and O, said heterocyclic ring optionally also comprising a carbonyl group and optionally also comprising 1-3 double bonds, wherein the point of attachment of said heterocyclic ring to the ring to which R a is attached is a carbon atom, wherein said heterocyclic ring is optionally substituted with 1-5 substituent groups independently selected from halogen, —C 1 -C 3 alkyl, and —OC 1 -C 3 alkyl, wherein —C 1 -C 3 alkyl and —OC 1 -C 3 alkyl are optionally substituted with 1-7 halogens;

wherein for compounds in which R a is selected from the group consisting of —C 1 -C 6 alkyl, —C 2 -C 6 alkenyl, —C 2 -C 6 alkynyl, —C 3 -C 8 cycloalkyl optionally having 1-3 double bonds, —OC 1 -C 6 alkyl, —OC 2 -C 6 alkenyl, —OC 2 -C 6 alkynyl, —OC 3 -C 8 cycloalkyl optionally having 1-3 double bonds, —C(═O)C 1 -C 6 alkyl, —C(═O)C 3 -C 8 cycloalkyl, —CO 2 C 1 -C 6 alkyl, —C(═O)SC 1 -C 6 alkyl, —NR 3 C(═O)OC 1 -C 6 alkyl, and —S(O) x C 1 -C 6 alkyl, then R a is optionally substituted with 1-15 halogens and is optionally also substituted with 1-3 substituent groups independently selected from (a) —OH, (b) —CN, (c) —NR 3 R 4 , (d) —C 3 -C 8 cycloalkyl optionally having 1-3 double bonds and optionally substituted with 1-15 halogens, (e) —OC 1 -C 4 alkyl optionally substituted with 1-9 halogens and optionally also substituted with 1-2 substituent groups independently selected from —OC 1 -C 2 alkyl and phenyl, (f) —OC 3 -C 8 cycloalkyl optionally having 1-3 double bonds and optionally substituted with 1-15 halogens, (g) —CO 2 H, (h) —C(═O)CH 3 , (i) —CO 2 C 1 -C 4 alkyl which is optionally substituted with 1-9 halogens, and (j) phenyl which is optionally substituted with 1-3 groups independently selected from halogen, —CH 3 , —CF 3 , —OCH 3 , and —OCF 3 ;

with the proviso that when B is A 1 , and X and Y are —CH 2 —, and Z is —C(═O)—, and R 2 is phenyl which has a substituent R a in the 4-position, wherein R a is —OC 1 -C 6 alkyl which is optionally substituted as described above, then there are no other Ra substitutents on R 2 in which R a is selected from —OH, —OC 1 -C 6 alkyl, —OC 2 -C 6 alkenyl, —OC 2 -C 6 alkynyl, and —OC 3 -C 8 cycloalkyl optionally having 1-3 double bonds, optionally substituted as described above.

n is 0 or 1;

p is an integer from 0-4;

x is 0, 1, or 2;

y is 1 or 2;

R 3 and R 4 are each independently selected from H, —C 1 -C 5 alkyl, —C(═O)C 1 -C 5 alkyl and —S(O) y C 1 -C 5 alkyl, wherein —C 1 -C 5 alkyl in all instances is optionally substituted with 1-11 halogens; and

R 5 is selected from the group consisting of H, —OH, —C 1 -C 5 alkyl, and halogen, wherein —C 1 -C 5 alkyl is optionally substituted with 1-11 halogens.

2. The compound of claim 1 , which is selected from the group consisting of compounds having Formula Ia, Ib, and Id, or a pharmaceutically acceptable salt thereof:

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

Y is —(CRR 1 )—;

R and R 6 are each independently selected from the group consisting of H and —C 1 -C 5 alkyl, wherein —C 1 -C 5 alkyl is optionally substituted with 1-11 halogens;

R 1 is selected from the group consisting of H, —C 1 -C 5 alkyl, and —(C(R) 2 ) n A 2 , wherein —C 1 -C 5 alkyl is optionally substituted with 1-11 halogens;

Wherein one of B and R 2 is A 1 ; and one of B, R 1 , and R 2 is A 2 or —(C(R) 2 ) n A 2 ; so that the compound of Formula I comprises one group A 1 and one group A 2 ;

A 3 is selected from the group consisting of:

(a) an aromatic ring selected from phenyl and naphthyl;

(b) a 5-6-membered heterocyclic ring having 1-4 heteroatoms independently selected from N, S, O, and —N(O)—, and optionally also comprising 1-3 double bonds and a carbonyl group, wherein the point of attachment of A 3 to the phenyl ring to which A 3 is attached is a carbon atom; and

(c) a benzoheterocyclic ring comprising a phenyl ring fused to a 5-6-membered heterocyclic ring having 1-2 heteroatoms independently selected from O, N, and —S(O) x — and optionally 1-2 double bonds, wherein the point of attachment of A 3 to the phenyl ring to which A 3 is attached is a carbon atom;

A 2 is selected from the group consisting of:

(a) an aromatic ring selected from phenyl and naphthyl;

(b) a 5-6-membered heterocyclic ring having 1-4 heteroatoms independently selected from N, S, O, and —N(O)—, and optionally also comprising 1-3 double bonds and a carbonyl group;

(c) a benzoheterocyclic ring comprising a phenyl ring fused to a 5-6-membered heterocyclic ring having 1-2 heteroatoms independently selected from O, N, and S and optionally 1-2 double bonds; and

(d) a —C 3 -C 8 cycloalkyl ring optionally having 1-3 double bonds;

wherein A 3 and A 2 are each optionally substituted with 1-4 substituent groups independently selected from R a ;

Each R a is independently selected from the group consisting of —C 1 -C 6 alkyl, —C 2 -C 6 alkenyl, —C 3 -C 8 cycloalkyl optionally having 1-3 double bonds, —OC 1 -C 6 alkyl, —C(═O)C 1 -C 6 alkyl, —C(═O)H, —CO 2 H, —CO 2 C 1 -C 6 alkyl, —OH, —NR 3 R 4 , —NR 3 C(═O)OC 1 -C 6 alkyl, —S(O) x C 1 -C 6 alkyl, halogen, —CN, —NO 2 , and a 5-6-membered heterocyclic ring having 1-4 heteroatoms independently selected from N, S, and O, said heterocyclic ring optionally also comprising a carbonyl group and optionally also comprising 1-3 double bonds, wherein the point of attachment of said heterocyclic ring to the ring to which R a is attached is a carbon atom, wherein said heterocyclic ring is optionally substituted with 1-5 substituent groups independently selected from halogen, —C 1 -C 3 alkyl, and —OC 1 -C 3 alkyl, wherein —C 1 -C 3 alkyl and —OC 1 -C 3 alkyl are optionally substituted with 1-7 halogens;

wherein for compounds in which R a is selected from the group consisting of —C 1 -C 6 alkyl, —C 2 -C 6 alkenyl, —C 3 -C 8 cycloalkyl optionally having 1-3 double bonds, —OC 1 -C 6 alkyl, —C(═O)C 1 -C 6 alkyl, —CO 2 C 1 -C 6 alkyl, —NR 3 C(═O)OC 1 -C 6 alkyl, and —S(O) x C 1 -C 6 alkyl, R a is optionally substituted with 1-15 halogens and is optionally also substituted with one substituent group selected from (a) —OH, (b) —NR 3 R 4 , (c) —OC 1 -C 4 alkyl optionally substituted with 1-9 halogens and optionally also substituted with 1-2 substituent groups independently selected from —OC 1 -C 2 alkyl and phenyl, and (d) phenyl which is optionally substituted with 1-3 groups independently selected from halogen, —CH 3 , —CF 3 , —OCH 3 , and —OCF 3 ;

with the proviso that when B is A 1 , and X and Y are —CH 2 —, and Z is —C(═O)—, and R 2 is phenyl which has a substituent R a in the 4-position, wherein R a is —OC 1 -C 6 alkyl which is optionally substituted as described above, then there are no other R a substitutents on R 2 in which R a is —OH or —OC 1 -C 6 alkyl which is optionally substituted as described above;

p is an integer from 0-2;

R 3 and R 4 are each independently selected from H and —C 1 -C 5 alkyl, wherein —C 1 -C 5 alkyl in all instances is optionally substituted with 1-11 halogens; and

R 5 is selected from the group consisting of H, —OH, and —C 1 -C 5 alkyl, wherein —C 1 -C 5 alkyl is optionally substituted with 1-11 halogens.

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

Y is —(CRR 1 )—;

Z is selected from the group consisting of —C(═O)—, —S(O) 2 —, and —C(═N—R 9 )—, wherein R 9 is selected from the group consisting of H, —CN, and CH 3 ;

Each R is independently selected from the group consisting of H and C 1 -C 2 alkyl;

R 6 is selected from the group consisting of H and —C 1 -C 3 alkyl, wherein C 1 -C 3 alkyl is optionally substituted with 1-5 halogens;

R 1 is selected from the group consisting of H, —C 1 -C 3 alkyl, and —(C(R) 2 ) n A 2 , wherein —C 1 -C 3 alkyl is optionally substituted with 1-5 halogens;

R 2 is selected from the group consisting of H, —C 1 -C 3 alkyl, A 1 , and —(C(R) 2 ) n A 2 , wherein —C 1 -C 3 alkyl is optionally substituted with 1-5 halogens;

Wherein one of B and R 2 is A 1 ; and one of B, R 1 , and R 2 is A 2 or —(C(R) 2 ) n A 2 ; so that the compound of Formula I comprises one group A 1 and one group A 2 ;

A 3 is selected from the group consisting of:

(a) phenyl;

(b) a 5-6-membered aromatic heterocyclic ring having 1-2 heteroatoms independently selected from N, S, O, and —N(O)—, wherein the point of attachment of A 3 to the phenyl ring to which A 3 is attached is a carbon atom; and

(c) a benzoheterocyclic ring comprising a phenyl ring fused to a 5-membered aromatic heterocyclic ring having 1-2 heteroatoms independently selected from O, N, and —S(O) x , wherein the point of attachment of A 3 to the phenyl ring to which A 3 is attached is a carbon atom;

A 2 is selected from the group consisting of:

(a) phenyl;

(b) a 5-6-membered heterocyclic ring having 1-4 heteroatoms independently selected from N, S, O, and —N(O)—, and optionally also comprising 1-3 double bonds;

(c) a benzoheterocyclic ring comprising a phenyl ring fused to a 5-membered heterocyclic ring having 1-2 heteroatoms independently selected from O, N, and S; and

(d) a —C 5 -C 6 cycloalkyl ring;

wherein A 3 and A 2 are each optionally substituted with 1-4 substituent groups independently selected from R a ;

Each R a is independently selected from the group consisting of —C 1 -C 4 alkyl, —C 2 -C 4 alkenyl, cyclopropyl, —OC 1 -C 2 alkyl, —C(═O)C 1 -C 2 alkyl, —C(═O)H, —CO 2 C 1 -C 4 alkyl, —OH, —NR 3 R 4 , —NR 3 C(═O)OC 1 -C 4 alkyl, —S(O) x C 1 -C 2 alkyl, halogen, —CN, —NO 2 , and a 5-6membered heterocyclic ring having 1-2 heteroatoms independently selected from N, S, and O, wherein the point of attachment of said heterocyclic ring to the ring to which R a is attached ring is a carbon atom, wherein said heterocyclic ring is optionally substituted with 1-5 substituent groups independently selected from halogen;

wherein for compounds in which R a is selected from the group consisting of —C 1 -C 4 alkyl, —C 2 -C 4 alkenyl, —OC 1 -C 2 alkyl, —C(═O)C 1 -C 2 alkyl, —CO 2 C 1 -C 4 alkyl, —NR 3 C(═O)OC 1 -C 4 alkyl, and —S(O) x C 1 -C 2 alkyl, the alkyl group of R a is optionally substituted with 1-5 halogens and is optionally also substituted with one substituent group selected from (a) —OH, (b) —NR 3 R 4 , (c) —OCH 3 optionally substituted with 1-3 fluorine atoms and optionally also substituted with one phenyl group, and (d) phenyl which is optionally substituted with 1-3 groups independently selected from halogen, —CH 3 , —CF 3 , —OCH 3 , and —OCF 3 ;

with the proviso that when B is A 1 , and X and Y are —CH 2 —, and Z is —C(═O)—, and R 2 is phenyl which has a substituent R a in the 4-position, wherein R a is —OC 1 -C 2 alkyl which is optionally substituted as described above, then there are no other Ra substitutents on R 2 in which R a is selected from —OH or —OC 1 -C 2 alkyl which is optionally substituted as described above;

p is an integer from 0-2; and

R 3 , R 4 , and R 5 are each independently selected from H and —C 1 -C 3 alkyl.

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

A 3 is selected from the group consisting of phenyl, thienyl, imidazolyl, pyrrolyl, pyrazolyl, pyridyl, N-oxido-pyridyl, thiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzothienyl, benzothienyl-S-oxide, and benzothienyl-S-dioxide; and

A 2 is selected from the group consisting of phenyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, pyrazolyl, 1,2,4-triazolyl, tetrazolyl, benzodioxolyl, pyridyl, N-oxido-pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, cyclopentyl, cyclohexyl, and tetrahydropyranyl.

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

X is selected from the group consisting of —O—, —NH—, and —N(C 1 -C 3 alkyl)-; and

Z is —C(═O)—.

7. The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein A 2 and A 3 are both phenyl; and

R a is selected from the group consisting of —C 1 -C 4 alkyl which is optionally substituted with 1-5 fluorine atoms and is optionally also substituted with one group selected from —OH and —OCH 3 ; —OC 1 -C 2 alkyl, which is optionally substituted with 1-3 fluorine atoms; —C 2 -C 4 alkenyl; —C 1 -C 2 alkyl which is substituted with one group —NR 3 R 4 ; —C 1 -C 2 alkyl-O—C 1 - C 2 alkyl-phenyl; cyclopropyl; —C(═O)H; —OH; —NR 3 R 4 ; —S(O) x C 1 -C 2 alkyl; halogen; —CN; —NO 2 ; and a 5-6-membered heterocyclic ring comprising 1-2 oxygen atoms which is optionally substituted with C 1 -C 2 alkyl;

subject to the same proviso as in claim 4 .

8. The compound of claim 7 having Formula Ii, or a pharmaceutically acceptable salt thereof, wherein:

R 7 is selected from the group consisting of Cl and —CF 3 ;

Each R b is independently selected from the group consisting of —C 1 -C 3 alkyl, —OCH 3 , and F;

R 1 is selected from the group consisting of H and —C 1 -C 2 alkyl;

R c is selected from the group consisting of halogen, —CH 3 , —CF 3 , and —CN;

q is 2 or 3; and

t is an integer from 0-2.

9. The compound of claim 7 having Formula Ij, or a pharmaceutically acceptable acceptable salt thereof, wherein:

R 7 is selected from the group consisting of Cl and —CF 3 ;

Each R b is independently selected from the group consisting of —C 1 -C 3 alkyl, —OCH 3 , and F;

R 1 is selected from the group consisting of H and —C 1 -C 2 alkyl;

R c is selected from the group consisting of halogen, —CH 3 , —CF 3 , and —CN;

q is 2 or 3; and

t is an integer from 0-2.

10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein

A 3 is phenyl, which is optionally substituted with 1-4 substituent groups R a , wherein R a is independently selected from —C 1 -C 5 alkyl, —OC 1 -C 3 alkyl, —CO 2 H, halogen, —NR 3 R 4 , —C(═O)C 1 -C 3 alkyl, —C(═O)H, —C(═O)NR 3 R 4 , —SC 1 -C 3 alkyl, —C 2 C 3 alkenyl, —CN, —NO 2 , and 1,2,4-oxadiazolyl, wherein —C 1 -C 3 alkyl and —C 1 -C 5 alkyl in all occurrences is optionally substituted with 1-6 substituents independently selected from 1-5 halogens and one —OH group; and —C 2 -C 3 alkenyl is optionally substituted with 1-3 halogens;

A 2 is selected from the group consisting of phenyl, cyclohexyl, and a heterocyclic 5-6 membered ring comprising 1-2 heteroatoms independently selected from O, N, S, and —N(O)— and optionally also comprising 1-3 double bonds, wherein A 2 is optionally substituted with 1-2 substituent groups independently selected from —C 1 -C 4 alkyl, —OC 1 -C 3 alkyl, —NO 2 , —CN, —S(O) x C 1 -C 3 alkyl, —NHS(O) 2 C 1 -C 3 alkyl, —NR 3 R 4 , —NR 3 C(═O)R 4 , —C 2 -C 3 alkenyl, —C(═O)NR 3 R 4 , halogen, and pyridyl, wherein C 1 -C 3 alkyl, C 1 -C 4 alkyl, and C 2 C 3 alkenyl in all instances is optionally substituted with 1-3 halogens;

X is O;

R 3 and R 4 are each independently selected from H and —C 1 -C 3 alkyl; and

p is 0-2.

11. The compound of claim 10 , or a pharmaceutically acceptable salt thereof, wherein A 1 is

R 7 and R 8 are each independently selected from the group consisting of H, halogen, —NR 3 R 4 , —C 1 -C 3 alkyl, —OC 1 -C 3 alkyl, —CN, —NO 2 , and pyridyl, wherein C 1 -C 3 alkyl in all instances is optionally substituted with 1-3 halogens;

A 2 is selected from the group consisting of phenyl, pyridyl, and cyclohexyl, wherein A 2 is optionally substituted with 1-2 substituents independently selected from —C 1 -C 4 alkyl, —OC 1 -C 3 alkyl, —NO 2 , —CN, and halogen, wherein C 1 -C 4 alkyl and C 1 -C 3 alkyl in all uses is optionally substituted with 1-3 halogens;

Z is —C(═O)—; and

R is H or —CH 3 .

12. The compound of claim 11 , or a pharmaceutically acceptable salt thereof, wherein A 1 is

R 7 is selected from the group consisting of H, halogen, —NR 3 R 4 , —C 1 -C 3 alkyl, —OC 1 -C 3 alkyl, —CN, —NO 2 , and pyridyl, wherein C 1 -C 3 alkyl in all instances is optionally substituted with 1-3 halogens; and

R 8 is selected from the group consisting of H, halogen, —CH 3 , —CF 3 , —OCH 3 , and —OCF 3 .

13. A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

14. The compound of claim 4 , which is selected from the group consisting of the following compounds, or a pharmaceutically acceptable salt thereof:

15. The compound of claim 4 , which is selected from the group consisting of compounds with the formula (a) to (c), or a pharmaceutically acceptable salt thereof:

16. The compound of claim 4 , which is selected from the group consisting of the following compounds, or a pharmaceutically acceptable salt thereof:

17. The compound of claim 4 , selected from the group consisting of compounds having the formula (a) to (k), or a pharmaceutically acceptable salt thereof:

wherein A 3 , A 2 , and Z for the compounds (1) to (6) are selected from the group Consisting of:

A 3

A 2

Z

(1)

CO

(2)

CO

(3)

CO

(4)

CO

(5)

CO and

(6)

SO 2 ;

(b)

wherein A 3 is selected from the group consisting of:

wherein A3 and A2 for the compounds (1) to (6) are selected from the group consisting of:

A 3

A 2

(1)

(2)

(3)

(4)

(5)

(6)

(d)

where R is selected from the group consisting of

where R is Et or n-Pr;

wherein R and A3 for the compounds (1) to (4) are selected from the group consisting of

R

A 3

(1)

(2)

(3)

(4)

(g)

where R is selected from the group consisting of

where A 2 is selected from the group consisting of

where R is selected from the group consisting of

where A 3 is selected from the group consisting of:

wherein A 3 , R 2 and R 3 for the compounds (1) to (3) are selected from the group consisting of:

A 3

R 2

R 3

(1)

Et

(2)

Et

(3)

Et

18. 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 to said patient, or a pharmaceutically acceptable salt thereof.

19. 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; and

(xvii) ileal bile acid transporters.

20. A compound which is (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[4'-fluoro-5'-isopropyl-2'-methoxy-4-(trifluoromethyl) biphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one having the structure

or a pharmaceutically acceptable salt thereof.

21. A pharmaceutical composition comprising the compound of claim 20 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

22. A pharmaceutical composition comprising the compound of claim 20 , or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable carrier, and one or more active ingredients selected from the group consisting of HMG-CoA reductase inhibitors and cholesterol absorption inhibitors.

23. The pharmaceutical composition of claim 22 , wherein the HMG-CoA reductase inhibitor is a statin selected from the group consisting of simvastatin, lovastatin, rosuvastatin, pravastatin, fluvastatin, atorvastatin, rivastatin, and itavastatin; and the cholesterol absorption inhibitor is ezetimibe.

24. 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 20 to said patient, or a pharmaceutically acceptable salt thereof.

25. 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 20 to said patient, or a pharmaceutically acceptable salt thereof, and one or more active ingredients selected from the group consisting of HMG-CoA reductase inhibitors and cholesterol absorption inhibitors.

26. The method of claim 25 , wherein the HMG-CoA reductase inhibitor is a statin selected from the group consisting of simvastatin, lovastatin, rosuvastatin, pravastatin, fluvastatin, atorvastatin, rivastatin, and itavastatin; and the cholesterol absorption inhibitor is ezetimibe.

27. A compound which is

28. A pharmaceutical composition comprising the compound of claim 27 and a pharmaceutically acceptable carrier.

29. A pharmaceutical composition comprising the compound of claim 27 , one or more active ingredients selected from the group consisting of HMG-CoA reductase inhibitors and cholesterol absorption inhibitors, and a pharmaceutically acceptable carrier.

30. The pharmaceutical composition of claim 29 , wherein the HMG-CoA reductase inhibitor is a statin selected from the group consisting of simvastatin, lovastatin, rosuvastatin, pravastatin, fluvastatin, atorvastatin, rivastatin, and itavastatin; and the cholesterol absorption inhibitor is ezetimibe.

31. 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 27 to said patient.

32. 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 27 to said patient and one or more active ingredients selected from the group consisting of HMG-CoA reductase inhibitors and cholesterol absorption inhibitors.

33. The method of claim 32 , wherein the HMG-CoA reductase inhibitor is a statin selected from the group consisting of simvastatin, lovastatin, rosuvastatin, pravastatin, fluvastatin, atorvastatin, rivastatin, and itavastatin; and the cholesterol absorption inhibitor is ezetimibe.

34. 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 HMG-CoA reductase inhibitors and cholesterol absorption inhibitors.

35. The pharmaceutical composition of claim 34 , wherein the HMG-CoA reductase inhibitor is a statin selected from the group consisting of simvastatin, lovastatin, rosuvastatin, pravastatin, fluvastatin, atorvastatin, rivastatin, and itavastatin; and the cholesterol absorption inhibitor is ezetimibe.

36. 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 to said patient, or a pharmaceutically acceptable salt thereof, and one or more active ingredients selected from the group consisting of HMG-CoA reductase inhibitors and cholesterol absorption inhibitors.

37. The method of claim 36 , wherein the HMG-CoA reductase inhibitor is a statin selected from the group consisting of simvastatin, lovastatin, rosuvastatin, pravastatin, fluvastatin, atorvastatin, rivastatin, and itavastatin; and the cholesterol absorption inhibitor is ezetimibe.

38. A pharmaceutical composition comprising the compound of claim 8 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

39. A pharmaceutical composition comprising the compound of claim 8 , or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable carrier, and one or more active ingredients selected from the group consisting of HMG-CoA reductase inhibitors and cholesterol absorption inhibitors.

40. The pharmaceutical composition of claim 39 , wherein the HMG-CoA reductase inhibitor is a statin selected from the group consisting of simvastatin, lovastatin, rosuvastatin, pravastatin, fluvastatin, atorvastatin, rivastatin, and itavastatin; and the cholesterol absorption inhibitor is ezetimibe.

41. 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 8 to said patient, or a pharmaceutically acceptable salt thereof.

42. 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 8 to said patient, or a pharmaceutically acceptable salt thereof, and one or more active ingredients selected from the group consisting of HMG-CoA reductase inhibitors and cholesterol absorption inhibitors.

43. The method of claim 42 , wherein the HMG-CoA reductase inhibitor is a statin selected from the group consisting of simvastatin, lovastatin, rosuvastatin, pravastatin, fluvastatin, atorvastatin, rivastatin, and itavastatin; and the cholesterol absorption inhibitor is ezetimibe.

44. A pharmaceutical composition comprising the compound of claim 10 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

45. A pharmaceutical composition comprising the compound of claim 10 , or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable carrier, and one or more active ingredients selected from the group consisting of HMG-CoA reductase inhibitors and cholesterol absorption inhibitors.

46. The pharmaceutical composition of claim 45 , wherein the HMG-CoA reductase inhibitor is a statin selected from the group consisting of simvastatin, lovastatin, rosuvastatin, pravastatin, fluvastatin, atorvastatin, rivastatin, and itavastatin; and the cholesterol absorption inhibitor is ezetimibe.

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 10 to said patient, or a pharmaceutically acceptable salt thereof.

48. 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 10 to said patient, or a pharmaceutically acceptable salt thereof, and one or more active ingredients selected from the group consisting of HMG-CoA reductase inhibitors and cholesterol absorption inhibitors.

49. The method of claim 48 , wherein the HMG-CoA reductase inhibitor is a statin selected from the group consisting of simvastatin, lovastatin, rosuvastatin, pravastatin, fluvastatin, atorvastatin, rivastatin, and itavastatin; and the cholesterol absorption inhibitor is ezetimibe.

50. A compound of formula Ie, or a pharmaceutically acceptable salt thereof,

wherein X is selected from the group consisting of —O—, —NH—, —N(C 1 -C 5 alkyl)— and —(CH 2 )—;

Z is selected from the group consisting of —C(═O)—, —S(O) 2 —, and —C(═N—R 9 )—, wherein R 9 is selected from the group consisting of H, —CN, and C 1 -C 5 alkyl optionally substituted with 1-11 halogens;

Each R is independently selected from the group consisting of H and —CH 3 ;

B is selected from the group consisting of A 1 and A 2 , wherein A 1 has the structure:

R 1 is selected from the group consisting of H, —C 1 —C 5 alkyl, and —(C(R) 2 ) n A 2 , wherein —C 1 —C 5 alkyl is optionally substituted with 1-11 halogens;

R 2 is selected from the group consisting of H, —C 1 —C 5 alkyl, A 1 , and —(C(R) 2 ) n A 2 , wherein —C 1 —C 5 alkyl is optionally substituted with 1-11 halogens;

Wherein one of B and R 2 is A 1 ; and one of B, R 1 , and R 2 is A 2 or —(C(R) 2 ) n A 2 , so that the compound of Formula Ie comprises one group A 1 and one group A 2 ;

A 2 is selected from the group consisting of phenyl, cyclohexyl, and pyridyl, wherein A 2 is optionally substituted with 1-2 substituent groups independently selected from halogen, —C 1 —C 4 alkyl, and —CN, wherein —C 1 —C 4 alkyl is optionally substituted with 1-3 halogens;

Each R a is independently selected from the group consisting of —C 1 —C 3 alkyl and halogen, wherein —C 1 —C 3 alkyl is optionally substituted with 1-3 halogens;

Each R b is independently selected from the group consisting of C1, F, —C 1 —C 4 alkyl, and —OC 1 -C 4 alkyl, wherein —C 1 —C 4 alkyl and —OC 1 -C 4 alkyl are optionally substituted with 1-5 F;

n is 0 or 1;

p is an integer from 0-2; and

q is an integer from 0-3.

51. The compound of claim 50 , which is selected from compounds having formula If, Ig, and Ih, or a pharmaceutically acceptable salt thereof:

wherein R 1 and R 2 are each independently selected from H and —C 1 —C 5 alkyl, wherein —C 1 —C 5 alkyl is optionally substituted with 1-11 halogens.

52. The compound of claim 51 , or a pharmaceutically acceptable salt thereof, wherein:

A 2 is selected from the group consisting of phenyl, cyclohexyl, and pyridyl, wherein A 2 is optionally substituted with 1-2 substituent groups independently selected from halogen, —CH 3 —CF 3 , and —CN;

Each R a is independently selected from the group consisting of —CF 3 and C1;

Each R b is independently selected from the group consisting of —C 1 —C 3 alkyl, —OCH 3 , and F;

R 1 and R 2 are each independently selected from the group consisting of H and —C 1 -C 2 alkyl;

X is selected from the group consisting of —O—, —NH—, —N(CH 3 )—, and —CH 2 —;

Z is selected from the group consisting of —C(═O)—, —S(O) 2 —, and —C(═N—CN)—;

p is 1; and

q is2or3.

53. The compound of claim 52 having formula If, or a pharmaceutically acceptable salt thereof:

54. The compound of claim 53 , or a pharmaceutically acceptable salt thereof, wherein:

X is O; and

Z is —C(═O)—.