1,3-oxazolidin-2-one derivatives useful as CETP inhibitors

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

Y is —(CRR 1 )—;

X is—O—;

Z is —C(═O)—;

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, A 1 ; wherein A 1 has the structure:

R 1 is 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;

R 2 is —(C(R) 2 ) n A 2 , wherein n is 0;

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;

wherein A 3 is substituted with one group A 4 and is optionally substituted with 1-4 groups R a ;

A 2 is phenyl,

wherein A 2 is optionally substituted with 1-5 substituent groups independently selected from R a ;

A 4 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; 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 when A 4 is (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 the heterocyclic ring to A 3 is a N atom of A 4 ; or (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; then A 4 is optionally substituted with 1-5 groups R a ;

and when A 4 is 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 the heterocyclic ring to A 3 is a carbon atom of A 4 , then A 4 is substituted with one group R e and is optionally also substituted with 1-4 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 doublebonds, —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, R a is optionally substituted with 1-15 halogens and is optionally 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 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 ;

Each R e is independently selected from the group consisting of —C 2 -C 6 alkenyl, —C 2 -C 6 alkynyl, —C 3 -C 8 cycloalkyl optionally having 1-3 double bonds, —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 , —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 e 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 e is selected from the group consisting of —C 2 -C 6 alkenyl, —C 2 -C 6 alkynyl, —C 3 -C 8 cycloalkyl optionally having 1-3 double bonds, —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, R e is optionally substituted with 1-15 halogens and is optionally 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 ;

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 of Formula Ia, or a pharmaceutically acceptable salt thereof:

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

R is 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 and —C 1 -C 5 alkyl, wherein —C 1 -C 5 alkyl is optionally substituted with 1-11 halogens;

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;

wherein A 3 is substituted with one group A 4 and is optionally substituted with 1-4 groups R a ;

A 2 is phenyl,

wherein A 2 is 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 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 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 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 ;

Each R e is independently selected from the group consisting of —C 2 -C 6 alkenyl, —C 3 -C 8 cycloalkyl optionally having 1-3 double bonds, —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, —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 e 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 e is selected from the group consisting of —C 2 -C 6 alkenyl, —C 3 -C 8 cycloalkyl optionally having 1-3 double bonds, —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 e is optionally substituted with 1-15 halogens and is optionally 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 ;

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:

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

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

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;

wherein A 3 is substituted with one group A 4 and is optionally substituted with 1-4 groups 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 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 5-6-membered 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 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 ;

Each R e is independently selected from the group consisting of —C 2 -C 4 alkenyl, cyclopropyl, —C(═O)C 1 -C 2 alkyl, —C(═O)H, —CO 2 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, —CN, —NO 2 , and a 5-6-membered 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 e is attached 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 e is selected from the group consisting of —C 2 -C 4 alkenyl, —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 e 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 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 ;

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 1 , or a pharmaceutically acceptable salt thereof, wherein

X is —O—;

Z is —C(═O)—;

Y is —CHR 1 , where R 1 is selected from H and C 1 -C 2 alkyl;

R and R 5 are H;

A 3 is selected from the group consisting of phenyl, thiazolyl, and pyrazolyl;

A 4 is selected from the group consisting of phenyl, pyridyl, thiazolyl, pyrazolyl, 1,2,4-triazolyl, pyrimidinyl, piperidinyl, pyrrolidinyl, and azetidinyl;

A 2 is optionally substituted with 1-3 substituents independently selected from halogen, —OCH 3 , —OCF 3 , and C 1 -C 3 alkyl optionally substituted with 1-3 halogens;

A 3 is substituted with one group A 4 and is optionally substituted with 1-2 substituents independently selected from halogen, —OH, —OCH 3 , —OCF 3 , and C 1 -C 3 alkyl optionally substituted with 1-3 halogens;

A 4 is optionally substituted with 1-3 substituents independently selected from the group consisting of (a) —C 1 -C 5 alkyl optionally substituted with 1-3 halogens and optionally substituted with —OH, (b) —C 2 -C 4 alkenyl optionally substituted with 1-3 halogens, (c) —C(═O)C 1 -C 2 alkyl optionally substituted with 1-3 halogens and optionally substituted with one group selected from —OH, —CO 2 CH 3 , —C(═O)CH 3 , —NR 3 R 4 , and —OC 1 -C 2 alkyleneOC 1 -C 2 alkyl, (d) —C(═O)H, (e) —CO 2 H, (f) —CO 2 C 1 -C 4 alkyl optionally substituted with one group selected from —C(═O)C 1 -C 2 alkyl, —OH, —CO 2 CH 3 , —CO 2 H, —NR 3 R 4 , and —OC 1 -C 2 alkyleneOC 1 -C 2 alkyl, (g) —OH, (h) —S(O) x C 1 -C 2 alkyl, (i) halogen, (j) —CN, (k) —NO 2 , (l) —C(═O)NR 3 R 4 , (m) —OC 1 -C 2 alkyleneOC 1 -C 2 alkyl, (n) —OC 1 -C 3 alkyl optionally substituted with 1-3 halogens, (o) —C(═O)OC 1 -C 2 alkyl optionally substituted with 1-3 halogens and optionally substituted with one group selected from —OH, —CO 2 CH 3 , —NR 3 R 4 , and —OC 1 -C 2 alkyleneOC 1 -C 2 alkyl, (p) —NR 3 C(═O)C 1 -C 2 alkyl, (q) —NR 3 R 4 , and (r) —S(O) x NR 3 R 4 ,

provided that if A 4 is a heterocyclic group connected to A 3 through a ring carbon atom of A 4 , then at least one substituent on A 4 must be selected from R e , where R e is selected from the group consisting of (a) —C 1 -C 5 alkyl substituted with —OH and optionally substituted with 1-3 halogens, (b) —C 2 -C 4 alkenyl optionally substituted with 1-3 halogens, (c) —C(═O)C 1 -C 2 alkyl optionally substituted with 1-3 halogens and optionally substituted with one group selected from —OH, —CO 2 CH 3 , —C(═O)CH 3 , —NR 3 R 4 , and —OC 1 -C 2 alkyleneOC 1 -C 2 alkyl, (d) —C(═O)H, (e) —CO 2 H, (f) —CO 2 C 1 -C 4 alkyl optionally substituted with one group selected from —C(═O)C 1 -C 2 alkyl, —OH, —CO 2 CH 3 , —CO 2 H, —NR 3 R 4 , and —OC 1 -C 2 alkyleneOC 1 -C 2 alkyl, (g) —OH, (h) —S(O) x C 1 -C 2 alkyl, (i) —CN, (j) —NO 2 , (k) —C(═O)NR 3 R 4 , (l) —OC 1 -C 2 alkyleneOC 1 -C 2 alkyl, (m) —C(═O)OC 1 -C 2 alkyl optionally substituted with 1-3 halogens and optionally substituted with one group selected from —OH, —CO 2 CH 3 , —NR 3 R 4 , and —OC 1 -C 2 alkyleneOC 1 -C 2 alkyl, (n) —NR 3 C(═O)C 1 -C 2 alkyl, (o) —NR 3 R 4 ; and (p) —S(O) x NR 3 R 4 ;

p is 0, 1, or 2; and

R a is selected from halogen, —CH 3 , —CF 3 , —OCH 3 , and —OCF 3 ;

R 3 and R 4 are each independently selected from H and CH 3 ; and

x is 0, 1 or 2.

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

Each R a is selected from the group consisting of (a) —C 1 -C 4 alkyl which is optionally substituted with 1-5 fluorine atoms and is optionally substituted with one group selected from —OH, —OCH 3 , and —NR 3 R 4 ; (b) —OC 1 -C 2 alkyl, which is optionally substituted with 1-3 fluorine atoms; (c) —C 2 -C 4 alkenyl; (d) —C 1 -C 2 alkyl-O—C 1 -C 2 alkyl-phenyl; (e) cyclopropyl; (f) —C(═O)H; (g) —CO 2 H; (h) —CO 2 C 1 -C 4 alkyl; (i) —OH; (j) —NR 3 R 4 ; (k) —S(O) x C 1 -C 2 alkyl; (l) halogen; (m) —CN; (n) —NO 2 ; and (o) a 5-6-membered heterocyclic ring comprising 1-2 oxygen atoms which is optionally substituted with C 1 -C 2 alkyl.

7. The compound of claim 1 of Formula Ic, or a pharmaceutically acceptable salt thereof,

wherein B 1 is:

and B 2 is Ar 1 (R c ) u ;

Ar 1 is phenyl;

Ar 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 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 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;

R 1 is 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;

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;

Each R a , R b , R c , and R d 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 , R b , R c , or R d 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 when R a , R b , R c , and R d are 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 , R b , R c , and R d are optionally substituted with 1-15 halogens and are optionally 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 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 ;

R e is selected from the group consisting of —C 2 -C 6 alkenyl, —C 2 -C 6 alkynyl, —C 3 -C 8 cycloalkyl optionally having 1-3 double bonds, —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 , —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 e 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 when R e is selected from the group consisting of —C 2 -C 6 alkenyl, —C 2 -C 6 alkynyl, —C 3 -C 8 cycloalkyl optionally having 1-3 double bonds, —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 e is optionally substituted with 1-15 halogens and is optionally 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 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 ;

p is an integer from 0-4;

q is an integer from 0-4;

u is an integer from 0-5;

x is 0, 1 or 2; and

y is 1 or 2;

wherein when Ar 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 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 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 the heterocyclic ring to the phenyl group to which the heterocyclic ring is attached is a heteroatom of the heterocyclic ring;

then t is an integer from 0-5, and w is 0;

and when Ar 2 is 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 the heterocyclic ring to the phenyl group to which the heterocyclic ring is attached is a carbon atom of the heterocyclic ring, then t is an integer from 0-4, and w is 1.

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

9. The compound of claim 8 of Formula Ig, or a pharmaceutically acceptable salt thereof, wherein

Each R d is independently selected from the group consisting of —C 1 -C 4 alkyl, —C 2 -C 4 alkenyl, cyclopropyl, —OC 1 -C 4 alkyl, —C(═O)C 1 -C 4 alkyl, —C(═O)H, —CO 2 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 5-6-membered 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 d is attached is a carbon atom, wherein said heterocyclic ring is optionally substituted with 1-5 substituent groups independently selected from halogen;

wherein when R d is selected from the group consisting of —C 1 -C 4 alkyl, —C 2 -C 4 alkenyl, cyclopropyl, —OC 1 -C 4 alkyl, —C(═O)C 1 -C 4 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, then the alkyl, alkenyl and cyclopropyl group of R d is optionally substituted with 1-5 halogens and is optionally 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 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 ; and

t is an integer from 0-5.

10. The compound of claim 9 of Formula Ih, or a pharmaceutically acceptable salt thereof:

11. The compound of claim 7 , or a pharmaceutically acceptable salt thereof:

wherein R 1 is 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 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;

Each R a , R b , and R c 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 when R a , R b , and R c are 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, then R a , R b and R d are optionally substituted with 1-15 halogens and are optionally 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 substituted with 1-2 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 ;

Each R d is independently 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, —C(═O)H, —CO 2 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 5-6-membered 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 is a carbon atom, wherein said heterocyclic ring is optionally substituted with 1-5 substituent groups independently selected from halogen;

wherein when R d 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, then the alkyl or alkenyl group of R d is optionally substituted with 1-5 halogens and is optionally substituted with one group selected from (a) —OH, (b) —NR 3 R 4 , (c) —OCH 3 optionally substituted with 1-3 fluorine atoms and optionally 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 ;

p is an integer from 0-2;

q is an integer from 0-2;

t is an integer from 0-3;

u is an integer from 0-2;

x is 0, 1 or 2; and

y is 1 or 2.

12. The compound of claim 7 , or a pharmaceutically acceptable salt thereof, wherein:

R 1 is selected from H and —C 1 -C 2 alkyl;

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

Each R a , R b , and R c is independently 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, —C(═O)H, —CO 2 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, and —NO 2 ;

wherein when R a , R b , and R c are selected from —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, then the alkyl and alkenyl groups of R a , R b , and R c are optionally substituted with 1-5 halogens and are optionally substituted with one group selected from (a) —OH, (b) —NR 3 R 4 , (c) —OCH 3 optionally substituted with 1-3 fluorine atoms and optionally 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 ;

R d is selected from the group consisting of —C 1 -C 4 alkyl, —C 2 -C 4 alkenyl, —NR 3 R 4 , —C(═O)H, —CO 2 H, —CO 2 C 1 -C 4 alkyl, —OH, halogen, —CN, and —NO 2 , wherein —C 1 -C 4 alkyl and —C 2 -C 4 alkenyl in all uses are optionally substituted with 1-5 fluorine atoms

p is an integer from 1-2;

q is an integer from 1-2;

t is an integer from 0-3;

u is an integer from 1-2; and

x is 0, 1 or 2.

13. The compound of claim 7 , or a pharmaceutically acceptable salt thereof, wherein

R 1 , R 3 and R 4 are each independently selected from H and CH 3 ;

R a , R b , and R c are each independently selected from the group consisting of —C 1 -C 3 alkyl, —OC 1 -C 2 alkyl, halogen and —OH, wherein —C 1 -C 3 alkyl and —OC 1 -C 2 alkyl are optionally substituted with 1-3 F;

R d is selected from the group consisting of —C 1 -C 3 alkyl, —NR 3 R 4 , —CO 2 H, —CO 2 C 1 -C 3 alkyl, halogen, and —CN, wherein —C 1 -C 3 alkyl and —CO 2 C 1 -C 3 alkyl are optionally substituted with 1-3 F;

p is an integer from 1-2;

q is an integer from 1-2;

t is an integer from 0-3; and

u is an integer from 1-2.

14. The compound of claim 7 , or a pharmaceutically acceptable salt thereof, wherein Ar 2 is selected from the group consisting of phenyl, pyridyl, pyrimidyl, pyrazinyl, pyrazolyl, pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thienyl, furyl, benzothiophenyl, benzoxazolyl, benzisoxazolyl, and benzofuryl.

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

16. The compound of claim 1 , which is selected from the group consisting of the following compounds, or a pharmaceutically acceptable salt thereof:

17. The compound of claim 1 , which is selected from the group consisting of the following compounds, or a pharmaceutically acceptable salt thereof:

wherein R 1 is selected from the group consisting of:

wherein R is selected from the group consisting of:

57

Me, and

58

Cl;

wherein R is selected from the group consisting of:

wherein R is selected from the group consisting of:

63

CF3 and

64

Me;

wherein R x is selected from the group consisting of:

wherein R is selected from the group consisting of:

wherein R is selected from the group consisting of:

wherein R x is selected from the group consisting of:

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

19. 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.

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

21. 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.