A compound of formula: or tautomer thereof, or their pharmaceutically acceptable salts, wherein: Z 1, Z 2 and Z 3 are each independently N (nitrogen), N R 7 or C R 8, wherein at least one of Z 1, Z 2 or Z 3 is N R 7; R 7 is -C(= Y)N R 1 R 2; R 8 is hydrogen, halo, (C 1 -C 6)alkyl optionally substituted with up to 5 fluoro, or (C 1 -C 6)alkoxy optionally substituted with up to 5 fluoro; Y is O (oxygen) or S (sulfur); R 1 and R 2 are each independently selected from the group consisting of hydrogen, (C 1 -C 6)alkyl, (C 2 -C 6)alkenyl, (C 2 -C 6)alkynyl, hydroxy(C 1 -C 6)alkyl, (C 1 -C 6)alkylO R a, (C 1 -C 6)alkyl optionally substituted with up to 5 fluoro, (C 1 -C 6)alkyl optionally substituted with up to 5 chloro, (C 1 -C 6)alkoxy optionally substituted with up to 5 fluoro, (C 1 -C 6)alkylN R a R b, and aryl, or R 1 and R 2 are taken together with the nitrogen to which they are attached to form a heterocycle group optionally substituted with one or more R c; wherein the heterocycle group optionally include one or more groups selected from O (oxygen), S x, and N R d; x is 0,1 or 2; Ar is aryl, or heteroaryl, each optionally substituted with one or more M; R 3 is hydrogen or oxide; R 4 is selected from the group consisting of hydrogen, hydroxy, halo, hydroxy(C 1 -C 6)alkyl, (C 1 -C 6)alkyl optionally substituted with up to 5 fluoro, and (C 1 -C 6)alkoxy optionally substituted with up to 5 fluoro; each R a and R b is independently hydrogen, (C 1 -C 6)alkyl, aryl, heteroaryl, heterocycle, (C 1 -C 6)alkylaryl, -S x (C 1 -C 6)alkyl, -S x aryl, or -C (C 1 -C 6)alkyl; each R c is independently hydrogen, aryl, heteroaryl, heterocycle or (C 1 -C 6)alkyl optionally substituted with up to 5 fluoro; each R d is independently hydrogen, halo, oxo, hydroxy, -C N R e R f, cyano, nitro, hydroxy(C 1 -C 6)alkyl, aryl, aryl(C 1 -C 6)alkyl, (C 1 -C 6)alkyl optionally substituted with up to 5 fluoro, (C 1 -C 6)alkoxy optionally substituted with up to 5 fluoro, or (C 1 -C 6) alkyl substituted with one or more R dd; R dd is hydroxyl, alkoxy, alkylamino or halo; each M is independently hydrogen, halo, CF 3, CF 2 H, hydroxy, methoxy, trifluoromethoxy, cyano, nitro, (C 1 -C 6)alkyl, hydroxy(C 1 -C 6)alkyl, (C 1 -C 6)alkoxy, -N R a R b, aryl, heteroaryl or heterocycle; and each R e and R f is independently (C 1 -C 6)alkyl. Z 1, Z 2 and Z 3 are each independently N (nitrogen), N R 7 or C R 8, wherein at least one of Z 1, Z 2 or Z 3 is N R 7; R 7 is -C(= Y)N R 1 R 2; R 8 is hydrogen, halo, (C 1 -C 6)alkyl optionally substituted with up to 5 fluoro, or (C 1 -C 6)alkoxy optionally substituted with up to 5 fluoro; Y is O (oxygen) or S (sulfur); R 1 and R 2 are each independently selected from the group consisting of hydrogen, (C 1 -C 6)alkyl, (C 2 -C 6)alkenyl, (C 2 -C 6)alkynyl, hydroxy(C 1 -C 6)alkyl, (C 1 -C 6)alkylO R a, (C 1 -C 6)alkyl optionally substituted with up to 5 fluoro, (C 1 -C 6)alkyl optionally substituted with up to 5 chloro, (C 1 -C 6)alkoxy optionally substituted with up to 5 fluoro, (C 1 -C 6)alkylN R a R b, and aryl, or R 1 and R 2 are taken together with the nitrogen to which they are attached to form a heterocycle group optionally substituted with one or more R c; wherein the heterocycle group optionally include one or more groups selected from O (oxygen), S x, and N R d; x is 0,1 or 2; Ar is aryl, or heteroaryl, each optionally substituted with one or more M; R 3 is hydrogen or oxide; R 4 is selected from the group consisting of hydrogen, hydroxy, halo, hydroxy(C 1 -C 6)alkyl, (C 1 -C 6)alkyl optionally substituted with up to 5 fluoro, and (C 1 -C 6)alkoxy optionally substituted with up to 5 fluoro; each R a and R b is independently hydrogen, (C 1 -C 6)alkyl, aryl, heteroaryl, heterocycle, (C 1 -C 6)alkylaryl, -S x (C 1 -C 6)alkyl, -S x aryl, or -C (C 1 -C 6)alkyl; each R c is independently hydrogen, aryl, heteroaryl, heterocycle or (C 1 -C 6)alkyl optionally substituted with up to 5 fluoro; each R d is independently hydrogen, halo, oxo, hydroxy, -C N R e R f, cyano, nitro, hydroxy(C 1 -C 6)alkyl, aryl, aryl(C 1 -C 6)alkyl, (C 1 -C 6)alkyl optionally substituted with up to 5 fluoro, (C 1 -C 6)alkoxy optionally substituted with up to 5 fluoro, or (C 1 -C 6) alkyl substituted with one or more R dd; R dd is hydroxyl, alkoxy, alkylamino or halo; each M is independently hydrogen, halo, CF 3, CF 2 H, hydroxy, methoxy, trifluoromethoxy, cyano, nitro, (C 1 -C 6)alkyl, hydroxy(C 1 -C 6)alkyl, (C 1 -C 6)alkoxy, -N R a R b, aryl, heteroaryl or heterocycle; and each R e and R f is independently (C 1 -C 6)alkyl.