A compound of Formula or an N-oxide thereof, or a pharmaceutically acceptable salt, solvate, polymorph or tautomer of said compound of Formula or N-oxide thereof: wherein R 7 is halo; Z 1 is absent, O, N(R a), or C(R b R c); X is C(R 0) or N, in which R 0 is H, D, or CF 3; each of Z 2, and Z 3, independently, is absent, O, (CH 2) p O, O(CH 2) p O, N, (CH 2) p, S, C, SO 2, OC, C O, OSO 2, S 2 O, C S, SC, C C, C N, N C, S 2 N, N S 2, OC O, OC S, OC N, N C O, N C S, N C N, (CH 2) p N (CH 2) q, (CH 2) p O(CH 2) q, (CH 2) p N C (CH 2) q, (CH 2) p C N (CH 2) q, OC N (CH 2) p+1 N (CH 2) q, a bivalent alkenyl group, or a bivalent alkynyl group; each of R 1, R 2, R 3, R 4, R 5, and R 6, independently, is H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl, halo, nitro, oxo, cyano,-(CH 2) p R a, -OR a, -SR a, -NH(CH 2) p R a, -C R a, -S R a, -SO 2 R a, -C OR a, -OC R a, -NR b R c,-P R b R c, -C N(R b)R c, -N(R b)C R c, -SO 2 N(R b)R c, or -N(R b)SO 2 R c, in which said alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl is optionally subsitiuted with one or more R d; each of p, and q, independently, is 0, 1, 2, 3, 4, 5, 6, 7, or 8; R a, R b, R c and R d, independently, is H, D, alkyl, alkenyl, alkynyl, halo, cyano, amine, nitro, hydroxy, C NHOH, alkoxy, alkoxyalkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkylcarbonyl, alkoxycarbonyl, alkylcarbonylamino, alkylamino, oxo, halo-alkylamino, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, or heteroaryl; R 4 and R 5, together with the atoms to which they are attached form an optionally substituted cycloalkyl or heterocycloalkyl; and R 1 and R 6, together with the atoms to which they are attached form an optionally substituted cycloalkyl or heterocycloalkyl. R 7 is halo; Z 1 is absent, O, N(R a), or C(R b R c); X is C(R 0) or N, in which R 0 is H, D, or CF 3; each of Z 2, and Z 3, independently, is absent, O, (CH 2) p O, O(CH 2) p O, N, (CH 2) p, S, C, SO 2, OC, C O, OSO 2, S 2 O, C S, SC, C C, C N, N C, S 2 N, N S 2, OC O, OC S, OC N, N C O, N C S, N C N, (CH 2) p N (CH 2) q, (CH 2) p O(CH 2) q, (CH 2) p N C (CH 2) q, (CH 2) p C N (CH 2) q, OC N (CH 2) p+1 N (CH 2) q, a bivalent alkenyl group, or a bivalent alkynyl group; each of R 1, R 2, R 3, R 4, R 5, and R 6, independently, is H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl, halo, nitro, oxo, cyano,-(CH 2) p R a, -OR a, -SR a, -NH(CH 2) p R a, -C R a, -S R a, -SO 2 R a, -C OR a, -OC R a, -NR b R c,-P R b R c, -C N(R b)R c, -N(R b)C R c, -SO 2 N(R b)R c, or -N(R b)SO 2 R c, in which said alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl is optionally subsitiuted with one or more R d; each of p, and q, independently, is 0, 1, 2, 3, 4, 5, 6, 7, or 8; R a, R b, R c and R d, independently, is H, D, alkyl, alkenyl, alkynyl, halo, cyano, amine, nitro, hydroxy, C NHOH, alkoxy, alkoxyalkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkylcarbonyl, alkoxycarbonyl, alkylcarbonylamino, alkylamino, oxo, halo-alkylamino, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, or heteroaryl; R 4 and R 5, together with the atoms to which they are attached form an optionally substituted cycloalkyl or heterocycloalkyl; and R 1 and R 6, together with the atoms to which they are attached form an optionally substituted cycloalkyl or heterocycloalkyl.