| abstract |
The present invention is in the field of medicine,nparticularly in the treatment of Type II diabetes andnobesity. More specifically, the present invention relatesnto selective b 3 receptor agonists useful in the treatment ofnType II diabetes and obesity. The invention providesncompounds and methods of treating type II diabetes andnobesity, comprising administering to a mammal in neednthereof compounds of the Formula I:n nwherein:n X 1 is -OCH 2 -, -SCH 2 -, or a bond; R 1 is a heterocycle of the formula:n R 2 and R 3 are independently hydrogen, C 1 -C 4 alkyl,nor aryl; R 4 is an optionally substituted heterocycle or anmoiety selected from the group consisting of: n X 2 is a bond, or a 1 to 5 carbon straight ornbranched alkylene; R 5 is hydrogen or C 1 -C 4 alkyl; R 6 is hydrogen or C 1 -C 4 alkyl; or R 5 and R 6 combine with the carbon to which eachnis attached to form a C 3 -C 6 cycloalkyl; or R 6 combines with X 2 and the carbon to whichneach is attached to form a C 3 -C 8 cycloalkyl; or R 6 combines with X 2 , R 4 , and the carbon tonwhich each is attached to form:n nprovided that R 5 is hydrogen; R 7 is hydrogen, hydroxy, cyano, oxo, CO n R 2 ,nCONHR 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 noptionally substituted alkyl, (CH 2 ) n aryl,n(CH 2 ) n heterocycle, (CH 2 ) n optionally substituted aryl, orn(CH 2 ) n optionally substituted heterocycle; R 8 is independently hydrogen, halo, or C 1 -C 4 nalkyl; R 9 is halo, CN, OR 10 , C 1 -C 4 alkyl, C 1 -C 4 nhaloalkyl, CO 2 R 2 , CONR 11 R 12 , CONH(C 1 -C 4 alkyl or C 1 -C 4 nalkoxy), SR 2 , CSNHR 2 , CSNR 11 R 12 , SO 2 R 2 , SOR 2 , NR 11 R 12 ,noptionally substituted aryl, optionally substitutednheterocycle, or C 2 -C 4 alkenyl substituted with CN, CO 2 R 2 , ornCONR 11 R 12 ; R 10 is C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, (CH 2 ) n C 3 -C 8 ncycloalkyl, (CH 2 ) n aryl, (CH 2 ) n heterocycle, (CH 2 ) n C 3 -C 8 noptionally substituted cycloalkyl, (CH 2 ) n optionallynsubstituted aryl, or (CH 2 ) n optionally substitutednheterocycle; R 11 and R 12 are independently hydrogen, C 1 -C 4 nalkyl, aryl, (CH 2 ) n aryl, or combine with the nitrogen tonwhich each is bound to form morpholinyl, piperidinyl,npyrrolidinyl, or piperazinyl; R 13 is hydrogen, halo, aryl, or C 1 -C 4 alkyl; m is 0 or 1; n is 0, 1, 2, or 3; nor a pharmaceutically acceptable salt thereof. |