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

A compound represented by formula I:

• or a pharmaceutically acceptable salt or solvate thereof is disclosed wherein:
• X represents CH2, O, S, S(O), SO2 or NH, such that when X represents NH, the nitrogen atom may be optionally substituted with R6, C(O)R6, or SO2R6, wherein:
• R6 represents C1-3alkyl optionally substituted with 1-3 groups, 0-3 of which are halo, and 0-1 of which are selected from the group consisting of:
• OC1-3alkyl, OH, NH2, NHC1-3alkyl, N(C1-3alkyl)2, CN, Hetcy, Aryl and HAR,
• said Aryl and HAR being further optionally substituted with 1-3 groups, 1-3 of which are halo, and 0-1 of which are selected from the group consisting of OH, NH2, C1-3alkyl, C1-3alkoxy, haloC1-3alkyl and haloC1-3alkoxy groups;
• a and b are each integers 1, 2 or 3, such that the sum of a and b is 2, 3 or 4;
• ring A represents a 6-10 membered aryl, a 5-13 membered heteroaryl or a partially aromatic heterocyclic group, said heteroaryl and partially aromatic heterocyclic group containing at least one heteroatom selected from O, S, S(O), S(O)2 and N, and optionally containing 1 other heteroatom selected from O and S, and optionally containing 1-3 additional N atoms, with up to 5 heteroatoms being present;
• each R2 and R3 is independently H, C1-3alkyl, haloC1-3alkyl, OC1-3alkyl, haloC1-3alkoxy, OH or F;
• n represents an integer of from 1 to 5;
• each R4 is H or is independently selected from halo and R6;
• R5 represents —CO2H,
• or —C(O)NHSO2Re wherein Re represents C1-4alkyl or phenyl, said C1-4alkyl and phenyl each being optionally substituted with 1-3 groups, 1-3 of which are selected from halo and C1-3alkyl, and 1-2 of which are selected from the group consisting of:
• OC1-3alkyl, haloC1-3alkyl, haloC1-3alkoxy, OH, NH2 and NHC1-3alkyl;
• and each R1 is H or is independently selected from the group consisting of:
• a) halo, OH, CO2H, CN, NH2, S(O)0-2Re, C(O)Re, OC(O)Re and CO2Re, wherein Re is as previously defined;
• b) C1-6 alkyl and OC1-6alkyl, said C1-6alkyl and alkyl portion of OC1-6alkyl being optionally substituted with 1-3 groups, 1-3 of which are halo and 1-2 of which are selected from:
• OH, CO2H, CO2C1-4alkyl, CO2C1-4haloalkyl, OCO2C1-4alkyl, NH2, NHC1-4alkyl, N(C1-4alkyl)2, Hetcy and CN;
• c) NHC1-4alkyl and N(C1-4alkyl)2, the alkyl portions of which are optionally substituted as set forth in (b) above;
• d) C(O)NH2, C(O)NHC1-4alkyl, C(O)N(C1-4alkyl)2, C(O)Hetcy, C(O)NHOC1-4alkyl and C(O)N(C1-4alkyl)(OC1-4alkyl), the alkyl portions of which are optionally substituted as set forth in (b) above;
• e) NR′C(O)R″, NR′SO2R″, NR′CO2R″ and NR′C(O)NR″R″′ wherein:
• R′ represents H, C1-3alkyl or haloC1-3alkyl,
• R″ represents (a) C1-8alkyl optionally substituted with 1-4 groups, 0-4 of which are halo, and 0-1 of which are selected from the group consisting of:
• OC1-6alkyl, OH, CO2H, CO2C1-4alkyl, CO2C1-4haloalkyl, NH2, NHC1-4alkyl, N(C1-4alkyl)2, CN, Hetcy, Aryl and HAR,
• said Hetcy, Aryl and HAR being further optionally substituted with 1-3 halo, C1-4alkyl, C1-4alkoxy, haloC1-4alkyl or haloC1-4alkoxy groups;
• or
• (b) Hetcy, Aryl or HAR, each being optionally substituted with 1-3 members selected from the group consisting of:
• halo, C1-4alkyl, C1-4alkoxy, haloC1-4alkyl and haloC1-4alkoxy groups;
• and R″′ representing H or R″;
• f) phenyl or a 5-6 membered heteroaryl or a Hetcy group attached at any available ring atom and each being optionally substituted with 1-3 groups, 1-3 of which are selected from halo, C1-3alkyl and haloC1-3alkyl groups, and 1-2 of which are selected from OC1-3alkyl and haloOC1-3alkyl groups, and 0-1 of which is selected from the group consisting of:
• i) OH;
• CO2H;
• CN;
• NH2 and S(O)0-2Re wherein Re is as described above;
• ii) NHC1-4alkyl and N(C1-4alkyl)2, the alkyl portions of which are optionally substituted with 1-3 groups, 1-3 of which are halo and 1-2 of which are selected from:
• OH, CO2H, CO2C1-4alkyl, CO2C1-4haloalkyl, NH2, NHC1-4alkyl, N(C1-4alkyl)2 and CN;
• iii) C(O)NH2, C(O)NHC1-4alkyl, C(O)N(C1-4alkyl)2, C(O)NHOC1-4alkyl and C(O)N(C1-4alkyl)(OC1-4alkyl), the alkyl portions of which are optionally substituted as set forth in b) above;
• and
• iv) NR′C(O)R″, NR′SO2R″, NR′CO2R″ and NR′C(O)NR″R″′ wherein R′, R″ and R″′ are as described above.