2-((4-((s)-2-(4-chloro-2-fluorophenyl)-2-methylbenzo[d][1,3]dioxol-4-yl)piperidin-1-yl)methyl)-1-(((s)-oxetan-2-yl)methyl)-1h-imidazole derivatives as activators of the glp1 receptor for the treatment of obesity

A compound of formula (I):

• or a pharmaceutically acceptable salt thereof, wherein
• is a single or double bond;
• is
• wherein
• indicates the point of attachment to the rest of the molecule;
• W is O or CH2;
• X is O or CH2;
• R1 and R2 are each independently selected from H, C1-3-alkyl, halo and CN;
• R3 is selected from H and C1-3-alkyl;
• R4 and R5 are selected from:
• (aa) R4 is selected from H, C1-6-alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6-cycloalkyl, 4-10 membered heterocycloalkyl, phenyl, C3-6-cycloalkyl-C1-3-alkyl-, (4-10 membered heterocycloalkyl)-C1-3-alkyl-, phenyl-C1-3-alkyl-, halo, CN, NO2, OR4a, SR4a, C(O)R4b, C(O)NR4cR4d, C(O)NR4c(OR4a), C(O)NR4c(S(O)2R4b), C(O)NR4c(S(O)2NR4cR4d), NR4cOR4a, NR4cR4d, NR4c(C(O)R4b), NR4c(C(O)OR4a), N(OR4a)(C(O)R4b), NR4c(C(O)NR4cR4d), NR4c(C(O)NR4c(C(O)R4b)), NR4c(S(O)2R4), NR4c(S(O)2NR4cR4d), NR4c(C(O)NR4c(S(O)2R4b)), OC(O)R4b, OC(O)NR4cR4d, ONR4c(C(O)R4b), OS(O)2R4b, OP(O)(OR4e)(OR4f), S(O)OR4a, S(O)R4b, S(O)2R4b, S(O)2NR4cR4d, S(O)2OR4a, S(═NR4g)(O)R4b, S(═NR4g)(O)NR4cNR4d, P(O)(OR4e)(OR4f), and P(O)(OR4e)(R4f), wherein the C1-6-alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6-cycloalkyl, 4-10 membered heterocycloalkyl, phenyl, C3-6-cycloalkyl-C1-3-alkyl-, (4-10 membered heterocycloalkyl)-C1-3-alkyl-, and phenyl-C1-3-alkyl- of R4 are each optionally substituted with 1, 2, or 3 groups independently selected from halo, CN, NO2, OR4A, SR4A, C(O)R4B, C(O)NR4CR4D, C(O)NR4C(OR4A), C(O)NR4C(S(O)2R4B), C(O)NR4C(S(O)2NR4CR4D), NR4COR4A, NR4CR4D, NR4C(C(O)R4B), NR4C(C(O)OR4A), N(OR4A)(C(O)R4B), NR4C(C(O)NR4CR4D), NR4C(C(O)NR4C(C(O)R4B)), NR4C(S(O)2R4B), NR4C(S(O)2NR4CR4D), NR4C(C(O)NR4C(S(O)2R4B)), OC(O)R4B, OC(O)NR4CR4D, ONR4C(C(O)R4B), OS(O)2R4B, OP(O)(OR4E)(OR4F), S(O)OR4A, S(O)R4B, S(O)2R4B, S(O)2NR4CR4D, S(O)2OR4A, S(═NR4G)(O)R4B, S(═NR4G)(O)NR4CNR4D, P(O)(OR4E)(OR4F), and P(O)(OR4E)(R4F), and
• R5 is 5-10 membered heteroaryl or (5-10 membered heteroaryl)-C1-3-alkyl-, wherein the 5-10 membered heteroaryl and (5-10 membered heteroaryl)-C1-3-alkyl- are each substituted with C(O)OR5A or with a carboxylic acid isostere, and optionally with 1, 2, or 3 groups independently selected from halo, CN, NO2, OR5A, SR5A, C1-3-alkyl, C1-3-alkyl substituted with 1, 2 or 3 halo, C(O)R5B, C(O)NR5CR5D, C(O)NR5C(OR5A), C(O)NR5C(S(O)2R5B), C(O)NR5C(S(O)2NR5CR5D), NR5COR5A, NR5CR5D, NR5C(C(O)R5B), NR5C(C(O)OR5A), N(OR5A)(C(O)R5B), NR5C(C(O)NR5CR5D), NR5C(C(O)NR5C(C(O)R5B)), NR5C(S(O)2R5B), NR5C(S(O)2NR5CR5D), NR5C(C(O)NR5C(S(O)2R5B)), OC(O)R5B, OC(O)NR5CR5D, ONR5C(C(O)R5B), OS(O)2R5B, OP(O)(OR5E)(OR5F), S(O)OR5A, S(O)R5B, S(O)2R5B, S(O)2NR5CR5D, S(O)2OR5A, S(═NR5G)(O)R5B, S(═NR5G)(O)NR5CNR5D, P(O)(OR5E)(OR5F), and P(O)(OR5E)(R5F);
• or
• (bb) R4 is 5-10 membered heteroaryl or (5-10 membered heteroaryl)-C1-3-alkyl-, wherein the 5-10 membered heteroaryl and (5-10 membered heteroaryl)-C1-3-alkyl- are each substituted with C(O)OR4A or with a carboxylic acid isostere, and optionally with 1, 2, or 3 groups independently selected from halo, CN, NO2, OR4A, SR4A, C1-3-alkyl, C1-3-alkyl substituted with 1, 2 or 3 halo, C(O)R4B, C(O)NR4CR4D, C(O)NR4C(OR4A), C(O)NR4C(S(O)2R4B), C(O)NR4C(S(O)2NR4CR4D), NR4COR4A, NR4CR4D, NR4C(C(O)R4B), NR4C(C(O)OR4A), N(OR4A)(C(O)R4B), NR4C(C(O)NR4CR4D), NR4C(C(O)NR4C(C(O)R4B)), NR4C(S(O)2R4B), NR4C(S(O)2NR4CR4D), NR4C(C(O)NR4C(S(O)2R4B)), OC(O)R4B, OC(O)NR4CR4D, ONR4(C(O)R4B), OS(O)2R4B, OP(O)(OR4E)(OR4F), S(O)OR4A, S(O)R4B, S(O)2R4B, S(O)2NR4CR4D, S(O)2OR4A, S(═NR4G)(O)R4B, S(═NR4G)(O)NR4CNR4D, P(O)(OR4E)(OR4F), and P(O)(OR4E)(R4F), and
• R5 is selected from H, C1-6-alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6-cycloalkyl, 4-10 membered heterocycloalkyl, phenyl, C3-6-cycloalkyl-C1-3-alkyl, (4-10 membered heterocycloalkyl)-C1-3-alkyl-, phenyl-C1-3-alkyl-, halo, CN, NO2, OR5a, SR5a, C(O)R5b, C(O)NR5cR5d, C(O)NR5c(OR5a), C(O)NR5c(S(O)2R5b), C(O)NR5c(S(O)2NR5cR5d), NR5cOR5a, NR5cR5d, NR5c(C(O)R5b), NR5c(C(O)OR5a), N(OR5a)(C(O)R5b), NR5c(C(O)NR5cR5d), NR5c(C(O)NR5c(C(O)R5b)), NR5c(S(O)2R5b), NR5c(S(O)2NR5cR5d), NR5c(C(O)NR5c(S(O)2R5b)), OC(O)R5b, OC(O)NR5cR5d, ONR5c(C(O)R5b), OS(O)2R5b, OP(O)(OR5e)(OR5f), S(O)OR5a, S(O)R5b, S(O)2R5b, S(O)2NR5cR5d, S(O)2OR5a, S(═NR5g)(O)R5b, S(═NR5g)(O)NR5cNR5d, P(O)(OR5e)(OR5), and P(O)(OR5e)(R5), wherein the C1-6-alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6-cycloalkyl, 4-10 membered heterocycloalkyl, phenyl, C3-6-cycloalkyl-C1-3-alkyl-, (4-10 membered heterocycloalkyl)-C1-3-alkyl-, and phenyl-C1-3-alkyl- of R5 are each optionally substituted with 1, 2, or 3 groups independently selected from halo, CN, NO2, OR5A, SR5A, C(O)R5B, C(O)NR5CR5D, C(O)NR5C(OR5A), C(O)NR5C(S(O)2R5B), C(O)NR5C(S(O)2NR5CR5D), NR5COR5A, NR5CR5D, NR5C(C(O)R5B), NR5C(C(O)OR5A), N(OR5A)(C(O)R5B), NR5C(C(O)NR5CR5D), NR5C(C(O)NR5C(C(O)R5B)), NR5C(S(O)2R5B), NR5C(S(O)2NR5CR5D), NR5C(C(O)NR5C(S(O)2R5B)), OC(O)R5B, OC(O)NR5CR5D, ONR5C(C(O)R5B), OS(O)2R5B, OP(O)(OR5E)(OR5F), S(O)OR5A, S(O)R5B, S(O)2R5B, S(O)2NR5CR5D, S(O)2OR5A, S(═NR5G)(O)R5B, S(═NR5G)(O)NR5CNR5D, P(O)(OR5E)(OR5F), and P(O)(OR5E)(R5F);
• R6 is selected from (4-10 membered heterocycloalkyl)-C1-3-alkyl- and (5-10 membered heteroaryl)-C1-3-alkyl-, wherein the (4-10 membered heterocycloalkyl)-C1-3-alkyl- and (5-10 membered heteroaryl)-C1-3-alkyl- of R6 are each optionally substituted with 1, 2, or 3 groups independently selected from C1-6-alkyl, —OH, and halo;
• R4a, R4b, R4c, and R4d are each independently selected from H, C1-6-alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6-cycloalkyl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, and phenyl, wherein the C1-6-alkyl, C2-6 alkenyl, and C2-6 alkynyl of R4a, R4b, R4c, and R4d are each optionally substituted with 1, 2, or 3 groups independently selected from —OH and halo;
• and
• the C3-6-cycloalkyl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, and phenyl of R4a, R4b, R4c, and R4d are each optionally substituted with 1, 2, or 3 groups independently selected from C1-6-alkyl, —OH, and halo;
• R4c, R4f, and R4g are each independently selected from H and C1-6-alkyl;
• R4A, R4B, R4C, and R4D are each optionally substituted with 1, 2, or 3 groups independently selected from —OH, halo and —OC(O)—C1-15-alkyl;
• and the C3-6-cycloalkyl, 4-10 membered heterocycloalkyl, 4-10 membered heterocycloalkyl-C1-3-alkyl-, 5-10 membered heteroaryl, and phenyl of R4A, R4B, R4C, and R4D are each optionally substituted with 1, 2, or 3 groups independently selected from C1-6-alkyl, —OH, and halo;
• R4E, R4F, and R4G are each independently selected from H and C1-6-alkyl;
• R5a, R5b, R5c, and R5d are each independently selected from H, C1-6-alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6-cycloalkyl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, and phenyl, wherein the C1-6-alkyl, C2-6 alkenyl, and C2-6 alkynyl of R5a, R5b, R5c, and R5d are each optionally substituted with 1, 2, or 3 groups independently selected from —OH and halo;
• and
• the C3-6-cycloalkyl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, and phenyl of R5a, R5b, R5c, and R5d are each optionally substituted with 1, 2, or 3 groups independently selected from C1-6-alkyl, —OH, and halo;
• R5c, R5f, and R5g are each independently selected from H and C1-6-alkyl;
• R5A, R5B, R5C, and R5D are each optionally substituted with 1, 2, or 3 groups independently selected from —OH, halo and —OC(O)—C1-15-alkyl;
• and the C3-6-cycloalkyl, 4-10 membered heterocycloalkyl, 4-10 membered heterocycloalkyl-C1-3-alkyl-, 5-10 membered heteroaryl, and phenyl of R5A, R5B, R5C, and R5D are each optionally substituted with 1, 2, or 3 groups independently selected from C1-6-alkyl, —OH, and halo;
• and
• R5E, R5F, and R5G are each independently selected from H and C1-6-alkyl.