Benzofuran and dihydrobenzofuran derivatives useful as beta-3 adrenoreceptor agonists

A compound of Formula I:

• 323
• wherein:
• represents a single or double bond;
• R is hydroxy, oxo, halo, cyano, nitro, C1-C10 alkyl, C1-C10 haloalkyl, CF3, NR1R1, SR1, OR1, SO2R2, OCOR2, NR1COR2, COR2, NR1SO2R2, phenyl, or a 5- or 6-membered heterocyclic ring with from 1 to 4 heteroatoms selected from O, S, and N,
• each cyclic moiety being optionally substituted with one or more substituents independently selected from hydroxy, R1, halo, cyano, NR1R1, SR1, CF3, OR1, C3-C8 cycloalkyl, NR1COR2, COR2, SO2R2, OCOR2, NR1SO2R2, C1-C10 alkyl, and C1-C10 alkoxy;
• R1 is hydrogen or C1-C10 alkyl optionally substituted with 1 to 4 substituents each independently selected from hydroxy, halo, CO2H, CO2(C1-C10 alkyl), C1-C10 alkoxy, and phenyl optionally substituted with CO2H, CO2(C1-C10 alkyl) or C1-C10 alkyl;
• or
• C3-C8 cycloalkyl, phenyl or naphthyl, each optionally substituted with 1 to 4 substituents each independently selected from halo, nitro, oxo, C1-C10 alkyl, C1-C10 alkoxy, and C1-C10 alkylthio;
• R2 is R1, OR1, NR1R1 or a 5- or 6-membered heterocyclic ring with one or more heteroatoms selected from O, S, and N, said heterocyclic ring being optionally substituted with R1;
• Ar is phenyl optionally fused to a 5- or 6-membered heterocyclic ring containing 1 to 4 heteroatoms each independently selected from O, S, and N, wherein the heterocyclic ring in turn is optionally fused to another phenyl ring;
• or
• a 5- or 6-membered heterocyclic ring containing 1 to 4 heteroatoms each independently selected from N, S, and O, optionally fused to a phenyl ring;
• Y is C1-C10 alkyl optionally substituted with 1 to 4 substituents each independently selected from hydroxy, halo, CO2H, CO2(C1-C10alkyl), C1-C10alkoxy, C1-C10 alkylthio, and phenyl optionally substituted with CO2H, CO2(C1-C10 alkyl), or C1-C10 alkyl;
• or
• phenyl optionally fused to another phenyl ring or to a 5- or 6-membered heterocyclic ring containing 1 to 4 heteroatoms selected from N, S, and O;
• or
• a 5- or 6-membered heterocyclic ring containing one or more heteroatoms selected from N, S, and O, optionally fused to a phenyl ring;
• each cyclic moiety being optionally substituted with one or more substituents independently selected from COR2, halo, NO2, OR1, R1, SR1, NR1R1, (C1-C10 alkyl) OR2, phenyl or tetrazolo;
• a is 0, 1, 2, 3, 4, or 5;
• and
• d is 1 or 2;
• and pharmaceutically acceptable salts or esters thereof.