Niacin Receptor Agonists, Compositions Containing Such Compounds and Methods of Treatment

1 . A compound represented by formula I:

or a pharmaceutically acceptable salt or solvate thereof, wherein:

Y represents C or N;

R a and R b are independently H, C 1-3 alkyl, haloC 1-3 alkyl, OC 1-3 alkyl, haloC 1-3 alkoxy, OH or F;

n represents an integer of from 1 to 5;

R 1 represents —CO 2 H,

or —C(O)NHSO 2 R c ;

R c represents C 1-4 alkyl or phenyl, said C 1-4 alkyl or phenyl being optionally substituted with 1-3 substituent groups, 1-3 of which are selected from halo and C 1-3 alkyl, and 1-2 of which are selected from the group consisting of: OC 1-3 alkyl, haloC 1-3 alkyl, haloC 1-3 alkoxy, OH, NH 2 and NHC 1-3 alkyl;

X 1 through X 10 represent C or a heteroatom selected from O, S and N, with up to 6 such heteroatoms present;

when X 1 is present, 0-2 of X 1 - X 5 represent N and 0-1 represent O or S;

when X 1 is absent, 0-3 of X 2 -X 5 represent N and 0-1 represent O or S;

when X 10 is present, 0-2 of X 6 -X 10 represent N and 0-1 represent O or S;

when X 10 is absent, 0-3 of X 6 -X 9 represent N and 0-1 represent O or S;

when any of X 1 -X 10 is substituted, said X variable represents C;

when X 10 is absent and at least one of X 6 -X 9 is 0 and 2 of X 6 -X 9 are N, and all of X 1 through X 5 represent C, X 3 is unsubstituted or is substituted with a member selected from the group consisting of: F, Br, I or a moiety selected from the group consisting of:

a) OH; CO 2 H; CN; NH 2 ; S(O) 0-2 R c ;

wherein R c is as previously defined;

b) C 1-6 alkyl and OC 1-6 alkyl, said group being optionally substituted with 1-3 groups, 1-3 of which are halo and 1-2 of which are selected from: OH, CO 2 H, CO 2 C 1-4 alkyl, CO 2 C 1-4 haloalkyl, OCO 2 C 1-4 alkyl, NH 2 , NHC 1-4 alkyl, N(C 1-4 alkyl) 2 , Hetcy, CN;

R 1 represents H, C 1-3 alkyl or haloC 1-3 alkyl,

R″ represents (a) C 1-8 alkyl optionally substituted with 1-4 groups, 0-4 of which are halo, and 0-1 of which are selected from the group consisting of: OC 1-6 alkyl, OH, CO 2 H, CO 2 C 1-4 alkyl, CO 2 C 1-4 haloalkyl, OCO 2 C 1-4 alkyl, NH 2 , NHC 1-4 alkyl, N(C 1-4 alkyl) 2 , CN, Aryl and HAR,

said Aryl and HAR being further optionally substituted with 1-3 halo, C 1-4 alkyl, C 1-4 alkoxy, haloC 1-4 alkyl and haloC 1-4 alkoxy groups;

(b) Aryl or HAR, said Aryl and HAR being further optionally substituted with 1-3 halo, C 1-4 alkyl, C 1-4 alkoxy, haloC 1-4 alkyl and haloC 1-4 alkoxy groups;

and R′″ representing H or R″;

each R 3 represents H, halo, C 1-3 alkyl, OC 1-3 alkyl, haloC 1-3 alkyl, haloC 1-3 alkoxy, or S(O) y C 1-3 alkyl, wherein y is 0, 1 or 2, and

each R 4 represents H, halo, methyl, or methyl substituted with 1-3 halo groups.

2 . A compound in accordance with claim 1 wherein: Y represents C.

3 . A compound in accordance with claim 1 wherein R a and R b represent H or C 1-3 alkyl.

4 . A compound in accordance with claim 3 wherein one or both of R a and R b represents C 1-3 alkyl.

5 . A compound in accordance with claim 4 wherein one or both of R a and R b represents methyl.

6 . A compound in accordance with claim 1 wherein n represents an integer 1, 2 or 3.

7 . A compound in accordance with claim 6 wherein n represents 2.

8 . A compound in accordance with claim 1 wherein R 1 represents CO 2 H or tetrazolyl.

9 . A compound in accordance with claim 8 wherein R 1 represents CO 2 H.

10 . A compound in accordance with claim 1 wherein R 4 represents H or halo.

11 . A compound in accordance with claim 10 wherein R 4 represents H.

12 . A compound in accordance with claim 10 wherein R 4 represents halo.

13 . A compound in accordance with claim 12 wherein R 4 represents fluoro.

14 . A compound in accordance with claim 1 wherein ring A represents a ring selected from the group consisting of: phenyl, thiazole, oxadiazole, pyrazole and thiophene.

15 . A compound in accordance with claim 14 wherein ring A represents a ring selected from the group consisting of: thiazole, oxadiazole and pyrazole.

16 . A compound in accordance with claim 1 wherein ring B represents a ring selected from the group consisting of: phenyl, pyridyl, pyrimidinyl, oxadiazolyl, faranyl, pyrazolyl and oxazolyl.

17 . A compound in accordance with claim 1 wherein ring B represents a ring selected from the group consisting of: phenyl, pyridine, pyrimidine, oxadiazole, furan and pyrazole.

18 . A compound in accordance with claim 1 wherein ring B represents a phenyl, pyridyl, pyrimidinyl, oxazolyl or furanyl ring.

19 . A compound in accordance with claim 16 wherein ring B represents a phenyl or pyridyl ring.

20 . A compound in accordance with claim 19 wherein ring B represents a pyridyl ring.

21 . A compound in accordance with claim 1 wherein each R 2 represents H, F, Cl, or a moiety selected from the group consisting of

a) OH; CO 2 H; CN; NH 2 ;

b) C 1-3 alkyl and OC 1-3 alkyl, said group being optionally substituted with 1-3 groups, 1-3 of which are halo and 1 of which is selected from: OH, CO 2 H, CO 2 C 1-4 alkyl, CO 2 C 1-4 haloalkyl, NH 2 , NHCH 3 and N(CH 3 ) 2 ;

c) NHCH 3 and N(CH 3 ) 2 ;

d) C(O)NH 2 , C(O)NHCH 3 , C(O)N(CH 3 ) 2 , C(O)NHOCH 3 and C(O)N(CH 3 )(OCH 3 );

e) NR′C(O)R″, NR′SO 2 R″, NR′CO 2 R″ and NR′C(O)NR″R′″ wherein:

R′ represents H, CH 3 or haloC 1-2 alkyl,

R″ represents (a) C 1-2 alkyl optionally substituted with 1-3 groups, 0-3 of which are halo, and 0-1 of which are selected from the group consisting of: OCH 3 , OH, CO 2 H, CO 2 C 1-2 alkyl, CO 2 C 1-2 haloalkyl, OCO 2 C 1-2 alkyl, NH 2 , NHCH 3 , N(CH 3 ) 2 , CN and Aryl,

said Aryl being further optionally substituted with 1-3 halo, CH 3 , OCH 3 , haloC 1-2 alkyl and haloC 1-2 alkoxy groups;

(b) Aryl optionally substituted with 1-3 halo, CH 3 , OCH 3 , C 1-2 alkoxy, haloC 1-2 alkyl and haloC 1-2 alkoxy groups;

and R′″ represents H or R″.

22 . A compound in accordance with claim 1 wherein two R 2 taken in combination represent a fused phenyl ring or a 5-6 membered fused heterocycle containing 0-1 of S, 0-2 of O, and containing 0-4 of N, and the remaining R 2 group is H, F, Cl, or a moiety selected from the group consisting of

a) OH; CO 2 H; CN; NH 2 ;

b) C 1-3 alkyl and OC 1-3 alkyl, said group being optionally substituted with 1-3 groups, 1-3 of which are halo and 1 of which is selected from: OH, CO 2 H, CO 2 C 1-4 alkyl, CO 2 C 1-4 haloalkyl, NH 2 , NHCH 3 and N(CH 3 ) 2 ;

c) NHCH 3 and N(CH 3 ) 2 ;

d) C(O)NH 2 , C(O)NHCH 3 , C(O)N(CH 3 ) 2 , C(O)NHOCH 3 and C(O)N(CH 3 )(OCH 3 );

e) NR′C(O)R″, NR′SO 2 R″, NR′CO 2 R″ and NR′C(O)NR″R′″ wherein:

R′ represents H, CH 3 or haloC 1-2 alkyl,

R″ represents (a) C 1-2 alkyl optionally substituted with 1-3 groups, 0-3 of which are halo, and 0-1 of which are selected from the group consisting of: OCH 3 , OH, CO 2 H, CO 2 C 1-2 alkyl, CO 2 C 1-2 haloalkyl, OCO 2 C 1-2 alkyl, NH 2 , NHCH 3 , N(CH 3 ) 2 , CN and Aryl,

said Aryl being further optionally substituted with 1-3 halo, CH 3 , OCH 3 , haloC 1-2 alkyl and haloC 1-2 alkoxy groups;

(b) Aryl optionally substituted with 1-3 halo, CH 3 , OCH 3 , C 1-2 alkoxy, haloC 1-2 alkyl and haloC 1-2 alkoxy groups;

and R′″ represents H or R″;

said fused phenyl ring or heterocycle being fused at any available point and being optionally substituted with 1-3 halo, C 1-2 alkyl or haloC 1-2 alkyl groups, or 1-2 OC 1-2 alkyl or haloOC 1-2 alkyl groups, or 1 moiety selected from the group consisting of:

a) OH; CO 2 H; CN; NH 2 ;

b) NHCH 3 and N(CH 3 ) 2 , the alkyl portions of which are optionally substituted with 1-3 groups, 1-3 of which are halo and 1 of which is selected from: OH, CO 2 H, CO 2 C 1-2 alkyl, CO 2 C 1-2 haloalkyl, OCO 2 C 1-2 alkyl, NH 2 , NHCH 3 , N(CH 3 ) 2 , CN;

c) C(O)NH 2 , C(O)NHCH 3 , C(O)N(CH 3 ) 2 , C(O)NHOCH 3 and C(O)N(CH 3 )(OCH 3 ), the alkyl portions of which are optionally substituted as set forth in (b) above;

d) NR′C(O)R″, NR′SO 2 R″, NR′CO 2 R″ and NR′C(O)NR″R′″ wherein:

R′ represents H, C 1-2 alkyl or haloC 1-2 alkyl,

R″ represents (a) C 1-8 alkyl optionally substituted with 1-4 groups, 0-4 of which are halo, and 0-1 of which are selected from the group consisting of: OC 1-3 alkyl, OH, CO 2 H, CO 2 C 1-2 alkyl, CO 2 C 1-2 haloalkyl, OCO 2 C 1-2 alkyl, NH 2 , NHCH 3 , N(CH 3 ) 2 , CN and Aryl HAR,

said Aryl being further optionally substituted with 1-3 halo, CH 3 , OCH 3 , haloC 1-2 alkyl and haloC 1-2 alkoxy groups;

(b) Aryl or HAR, said Aryl and HAR being further optionally substituted with 1-3 halo, CH 3 , OCH 3 , haloC 1-2 alkyl and haloC 1-2 alkoxy groups;

and R′″ representing H or R″.

23 . A compound in accordance with claim 1 selected from Table 1 below:

TABLE 1

or a pharmaceutically acceptable salt or solvate thereof.

24 . A pharmaceutical composition comprising a compound in accordance with claim 1 in combination with a pharmaceutically acceptable carrier.

25 . A method of treating atherosclerosis in a human patient in need of such treatment comprising administering to the patient a compound of claim 1 in an amount that is effective for treating atherosclerosis.

26 . A method of treating dyslipidemia in a human patient in need of such treatment comprising administering to the patient a compound of claim 1 in an amount that is effective for treating dyslipidemias.