Heterocyclic beta-3 adrenergic receptor agonists

A method of treating type II diabetes in a mammal in need thereof which comprises providing to said mammal, an effective amount of a compound of Formula I having the structure

• wherein,
• (a) a 5-6 membered heterocyclic ring having 1-4 heteroatoms selected from O, N, and S, substituted with (R1)m;
• (b) a phenyl ring substituted with (R1)m;
• (c) a naphthyl ring substituted with (R1)m;
• or
• (d) a phenyl fused heterocycle selected from the group consisting of
• U is —OCH2— or a bond;
• V is O or a bond;
• W is O, S(O)a;
• NR2, or NCOR2;
• X is SO2, CO, —(CH2)b—, a bond, or Ar;
• Y is —NR3R4, Het, Ar, alkyl of 1-8 carbon atoms, or —O(CH2)dR5;
• R1 is alkyl of 1-8 carbon atoms, alkenyl of 2-7 carbon atoms, —OR6, halogen, cyano, trifluoromethyl, —CO2R6, —CONR6R7, —NHCOR6, or NHSO2R8;
• R2 is hydrogen, alkyl of 1-8 carbon atoms, or arylalkyl having 1-8 carbon atoms in the alkyl moiety;
• R3 and R4 are each, independently, hydrogen, alkyl of 1-8 carbon atoms, cycloalkyl of 3-8 carbon atoms, arylalkyl having 1-8 carbon atoms in the alkyl group, —(CH2)gR9, —(CH2)hCOR9, —(CH2)jCR10R11(CH2)jR9, or —(CH2)kCONR12R13;
• or R3 and R4 may be taken together together with the nitrogen to which they are attached to form a 3-7 membered saturated heterocycle, which may optionally contain 1-2 additional heteroatoms selected from O and S, and said heterocycle may optionally be substituted with R14;
• R5 is hydrogen;
• alkyl of 1-8 carbon atoms optionally substituted by 1-3 substituents selected from hydroxy, halogen, and aryl;
• cycloalkyl of 1-8 carbon atoms;
• Ar or Het;
• R6, R7, and R8 are each, independently, hydrogen, or alkyl of 1-8 carbon atoms, or aryl of 6-10 carbon atoms;
• R9 is hydrogen;
• alkyl optionally substituted with 1-3 substitutents selected from hydroxy, halogen, and aryl;
• cycloalkyl of 3-8 carbon atoms;
• Ar, or Het;
• R10 and R11 are each, independently, hydrogen, alkyl, or aryl optionally substituted with alkyl of 1-8 carbon atoms or halogen;
• or R10 and R11 are taken together to form a spiro fused cycloalkyl ring of 3-8 carbon atoms;
• R12 and R13 are each, independently, hydrogen, alkyl of 1-8 carbon atoms, aryl optionally substituted with alkyl of 1-8 carbon atoms or halogen;
• or R12 and R13 are taken together with the nitrogen to which they are attached to form a 3-7 membered saturated heterocycle, which may optionally contain 1-2 additional heteroatoms selected from O and S, and said heterocycle may optionally be substituted with R14;
• R14 is CO2R15 or aryl optionally substituted with a 1-3 substituents selected from —OR15 and cycloalkyloxy of 3-8 carbon atoms;
• R15 is alkyl of 1-8 carbon atoms or arylalkyl having 1-8 carbon atoms in the alkyl moiety;
• Ar is an aromatic ring system containing 1-2 carbocyclic aromatic rings having 6-10 carbon atoms optionally mono-, di-, or tri-substituted with R16;
• Het is (a) a 5-6 membered heterocyclic ring having 1-4 heteroatoms selected from O, S, and N which may be optionally mono- or di-substituted with R16;
• or (b) a heterocyclic ring system optionally mono- or di-substituted by R16 containing a 5-6 membered heterocyclic ring fused to one or two carbocyclic or heterocyclic rings such that the heterocyclic ring system contains 1-4 heteroatoms selected from O, S, and N;
• R16 is halogen, alkyl of 1-8 carbon atoms, —OR17, cycloalkyl of 3-8 carbon atoms, trifluoromethyl, cyano, —CO2R17, —CONR17R18, —SO2NR17R18, —NR19CONR17R18, —NR17R18, —NR17COR18, —NO2, —O(CH2)pCO2R17, —OCONR17R18, —O(CH2)qOR17, or a 5-6 membered heterocyclic ring containing 1-4 heteroatoms selected from O, S, and N;
• R17, R18, and R19 are each, independently, hydrogen, alkyl of 1-8 carbon atoms, arylalkyl having 1-8 carbon atoms in the alkyl moiety, or aryl optionally mono-, di-, or tri-substituted with halogen, cyano, nitro, hydroxy, alkyl of 1-8 carbon atoms, or alkoxy of 1-8 carbon atoms;
• or when R17 and R18 are contained on a common nitrogen, R17 and R18 may be taken together with the nitrogen to which they are attached to form a 3-7 membered saturated heterocycle, which may optionally contain 1-2 additional heteroatoms selected from O and S;
• a=0-2;
• b=1-6;
• d=0-3;
• g=0-6;
• h=0-6;
• j=0-6;
• k=0-6;
• m=0-2;
• p=1-6;
• q=1-6;
• or a pharmaceutically acceptable salt thereof.