Selective beta 3 adrenergic agonists

The present invention is in the field of medicine, particularly in the treatment of Type II diabetes and obesity. More specifically, the present invention relates to selective b3 receptor agonists useful in the treatment of Type II diabetes and obesity. The invention provides compounds and methods of treating type II diabetes and obesity, comprising administering to a mammal in need thereof compounds of the Formula I: wherein: X1 is -OCH2-, -SCH2-, or a bond; R1 is a heterocycle of the formula: R2 and R3 are independently hydrogen, C1-C4 alkyl, or aryl; R4 is an optionally substituted heterocycle or a moiety selected from the group consisting of: X2 is a bond, or a 1 to 5 carbon straight or branched alkylene; R5 is hydrogen or C1-C4 alkyl; R6 is hydrogen or C1-C4 alkyl; or R5 and R6 combine with the carbon to which each is attached to form a C3-C6 cycloalkyl; or R6 combines with X2 and the carbon to which each is attached to form a C3-C8 cycloalkyl; or R6 combines with X2, R4, and the carbon to which each is attached to form: provided that R5 is hydrogen; R7 is hydrogen, hydroxy, cyano, oxo, COnR2, CONHR2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 optionally substituted alkyl, (CH2)n aryl, (CH2)nheterocycle, (CH2)n optionally substituted aryl, or (CH2)n optionally substituted heterocycle; R8 is independently hydrogen, halo, or C1-C4 alkyl; R9 is halo, CN, OR10, C1-C4 alkyl, C1-C4 haloalkyl, CO2R2, CONR11R12, CONH(C1-C4 alkyl or C1-C4 alkoxy), SR2, CSNHR2, CSNR11R12, SO2R2, SOR2, NR11R12, optionally substituted aryl, optionally substituted heterocycle, or C2-C4 alkenyl substituted with CN, CO2R2, or CONR11R12; R10 is C1-C4 alkyl, C1-C4 haloalkyl, (CH2)nC3-C8 cycloalkyl, (CH2)naryl, (CH2)nheterocycle, (CH2)nC3-C8 optionally substituted cycloalkyl, (CH2)n optionally substituted aryl, or (CH2)n optionally substituted heterocycle; R11 and R12 are independently hydrogen, C1-C4 alkyl, aryl, (CH2)naryl, or combine with the nitrogen to which each is bound to form morpholinyl, piperidinyl, pyrrolidinyl, or piperazinyl; R13 is hydrogen, halo, aryl, or C1-C4 alkyl; m is 0 or 1; n is 0, 1, 2, or 3; or a pharmaceutically acceptable salt thereof.k