Gip receptor agonist compounds

A compound of the formula:

• wherein
• X is CH2, OCH2 or CH2CH2, Y is CHR18 and is a single bond, or
• X is CH, Y is CR18 and is a double bond, or
• X is CHR14, Y is CHR15, is a single bond and R14 and R15 together with the carbons to which they are attached form a fused cyclopropyl, or
• X is N, Y is CH and is a double bond, or
• X is CH, Y is N and is a double bond;
• R18 is H or CH3;
• A is
• R1 is an 8-, 9- or 10-membered N-containing bicyclic heterocycle, phenyl or a 5- or 6-membered N-containing heterocycle, wherein the heterocycle or phenyl is optionally substituted with 1 to 3 substituents independently selected from:
• CN,
• halo,
• C1-C4alkyl optionally substituted with OCH3,
• C1-C4haloalkyl,
• C1-C4alkoxy,
• C1-C4haloalkoxy,
• CD3,
• oxo,
• phenyl optionally substituted with 1 or 2 substituents independently selected from halo and OH,
• benzyl optionally substituted with OCH3,
• NHC(O)R16, and
• a 9-membered N-containing bicyclic heterocycle optionally substituted with CH3:
• R16 is NHC1-C4alkyl, C3-C6cycloalkyl, NHC3-C6cycloalkyl, pyridyl optionally substituted with halo or CH3, or phenyl optionally substituted with halo;
• R2 and R2′ are independently H, halo or OCH3;
• R3 is:
• i) a 5- or 6-membered N-containing heteroaryl optionally substituted with 1 or 2 substituents selected from:
• CH3, CD3, CHF2, OH and CH2CN, or
• ii) an 8- or 9-membered N-containing bicyclic heterocycle optionally substituted with 1 or 2 substituents selected from oxo, CH3 and halo:
• R4 and R5 are each CH3, or together form a cyclopropyl, cyclobutyl, oxetane, tetrahydrofuran, pyrrolidine or piperidine, wherein the cyclopropyl or cyclobutyl is optionally substituted with 1 or 2 halo and wherein the pyrrolidine or piperidine is optionally substituted with CH3;
• R6 is H, D, OH, CH3, CO2R10, or
• wherein R10 is H or C1-C4alkyl optionally substituted with OC(O)C1-C4alkyl or morpholine, R6′ is H, and R7 is a 5- or 6-membered N-containing heteroaryl, 9-membered N-containing heteroaryl or phenyl, wherein the heteroaryl or phenyl is optionally substituted with R8 or with R8 and R9, or
• R6 is D, R6′ is D and R7 is a 5- or 6-membered N-containing heteroaryl, 9-membered N-containing heteroaryl or phenyl, wherein the heteroaryl or phenyl is optionally substituted with R8 or with R8 and R9, or
• R6 and R7 together form a 9-membered N-containing bicyclic heterocycle optionally substituted with 1 to 3 substituents independently selected from:
• CH3, CF3 and oxo, and R6′ is H;
• R8 is CF3, CF2H, halo, cyclopropyl, CH3 or H;
• R9 is:
• i) a 4-, 5- or 6-membered heterocycle optionally substituted with 1 to 4 substituents independently selected from:
• halo,
• OH,
• C1-C4alkoxy,
• SO2NH2,
• a 4- to 6-membered heterocycle optionally substituted with CH3 or oxo,
• CN,
• C3-C6cycloalkyl,
• CD3,
• C1-C4haloalkyl,
• CR12R13OP(O)(OH)2
• oxo,
• C1-C4haloalkoxy,
• C(O)NR12R13,
• (CH2)mP(O)(R17)2, and
• C1-C4alkyl, wherein the C1-C4alkyl is optionally substituted with OH, OCH3,
• NR12R13, C(O)NR12R13, CN, a 4- to 6-membered heterocycle or C3-C4cycloalkyl optionally substituted with halo,
• ii) a 9- or 10-membered N-containing bicyclic heterocycle optionally substituted with 1 or 2 substituents independently selected from CN, oxo, C(O)O(CH3)3, OH, CH3, and halo,
• iii) C1-C4alkoxy,
• iv) C3-C5cycloalkyl,
• v) halo,
• vi) (CH2)nC(O)R11, wherein n is 0 or 1, R11 is OCH3, NR12R13 or a 4- to 6-membered heterocycle,
• vii) C1-C4alkyl optionally substituted with a 4- to 6-membered heterocycle, phenyl, NHS(O)2(CH3) or NR12R13, which heterocycle or phenyl is optionally substituted with CH3,
• viii) CN,
• ix) phenyl optionally substituted with 1 to 3 substituents independently selected from C(O)OH, (CH2)mP(O)(R17)2, NR12R13 and C1-C4alkyl, wherein the C1-C4alkyl is optionally substituted with OH, or
• x) (CH2)mP(O)(R17)2;
• R12 and R13 are independently H or CH3;
• each R17 is independently C1-C4alkyl;
• and
• m is 0 or 1;
• or a pharmaceutically acceptable salt thereof.