A compound having the structure of Formula I: or a pharmaceutically acceptable salt thereof, wherein: is a double bond or a single bond; Ar is an optionally substituted aryl or heteroaryl, wherein one, two, or three optional substituents are independently selected from halogen, hydroxyl, cyano, -C(O)NH 2 , -C(O)N(R a ) 2 , -C(O)O(R a ), -C(O)R a , -N(R a ) 2 , -O(R a ), C 3 -C 6 cycloalkyl, C 3 -C 7 heterocyclyl, optionally substituted C 1 -C 4 alkyl and optionally substituted C 2 -C 6 alkenyl; R 1 is H, halogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, -O(R a ), C 3 -C 6 cycloalkyl, C 3 -C 7 heterocyclyl or N(Ra) 2 ; X 1 and X 2 are each independently CH or N; Y 1 is (CH 2 ) n or C(O), with the proviso that Y 1 cannot be C(O) when Y 2 or Y 3 is C(O); Y 2 is CH 2 , C(O), S, SO 2 , O or NR a , with the provisos that: Y 2 cannot be C(O) when Y 1 or Y 3 is C(O); and is a single bond; Y 3 is CH 2 or C(O), with the provisos that: Y 3 cannot be C(O) when Y 1 or Y 2 is C(O); and is a single bond; or Y 2 and Y 3 are CH and is a double bond; Z is CH 2 , O, S or NH; R a in each instance is independently H, C 1 -C 4 alkyl or C 3 -C 6 cycloalkyl; m is 0, 1, 2 or 3; and n is 1 or 2. or a pharmaceutically acceptable salt thereof, wherein: is a double bond or a single bond; Ar is an optionally substituted aryl or heteroaryl, wherein one, two, or three optional substituents are independently selected from halogen, hydroxyl, cyano, -C(O)NH 2 , -C(O)N(R a ) 2 , -C(O)O(R a ), -C(O)R a , -N(R a ) 2 , -O(R a ), C 3 -C 6 cycloalkyl, C 3 -C 7 heterocyclyl, optionally substituted C 1 -C 4 alkyl and optionally substituted C 2 -C 6 alkenyl; R 1 is H, halogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, -O(R a ), C 3 -C 6 cycloalkyl, C 3 -C 7 heterocyclyl or N(Ra) 2 ; X 1 and X 2 are each independently CH or N; Y 1 is (CH 2 ) n or C(O), with the proviso that Y 1 cannot be C(O) when Y 2 or Y 3 is C(O); Y 2 is CH 2 , C(O), S, SO 2 , O or NR a , with the provisos that: Y 2 cannot be C(O) when Y 1 or Y 3 is C(O); and is a single bond; Y 3 is CH 2 or C(O), with the provisos that: Y 3 cannot be C(O) when Y 1 or Y 2 is C(O); and is a single bond; or Y 2 and Y 3 are CH and is a double bond; Z is CH 2 , O, S or NH; R a in each instance is independently H, C 1 -C 4 alkyl or C 3 -C 6 cycloalkyl; m is 0, 1, 2 or 3; and n is 1 or 2. is a double bond or a single bond; Ar is an optionally substituted aryl or heteroaryl, wherein one, two, or three optional substituents are independently selected from halogen, hydroxyl, cyano, -C(O)NH 2 , -C(O)N(R a ) 2 , -C(O)O(R a ), -C(O)R a , -N(R a ) 2 , -O(R a ), C 3 -C 6 cycloalkyl, C 3 -C 7 heterocyclyl, optionally substituted C 1 -C 4 alkyl and optionally substituted C 2 -C 6 alkenyl; R 1 is H, halogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, -O(R a ), C 3 -C 6 cycloalkyl, C 3 -C 7 heterocyclyl or N(Ra) 2 ; X 1 and X 2 are each independently CH or N; Y 1 is (CH 2 ) n or C(O), with the proviso that Y 1 cannot be C(O) when Y 2 or Y 3 is C(O); Y 2 is CH 2 , C(O), S, SO 2 , O or NR a , with the provisos that: Y 2 cannot be C(O) when Y 1 or Y 3 is C(O); and is a single bond; Y 2 cannot be C(O) when Y 1 or Y 3 is C(O); and is a single bond; Y 3 is CH 2 or C(O), with the provisos that: Y 3 cannot be C(O) when Y 1 or Y 2 is C(O); and is a single bond; or Y 3 cannot be C(O) when Y 1 or Y 2 is C(O); and is a single bond; or Y 2 and Y 3 are CH and is a double bond; Z is CH 2 , O, S or NH; R a in each instance is independently H, C 1 -C 4 alkyl or C 3 -C 6 cycloalkyl; m is 0, 1, 2 or 3; and n is 1 or 2. <EOS>