A compound having a structure: wherein Z is a heteroaryl group or R a R b NCO-; Y 1 and Y 2, independently, are N or CR c; Y 3 and Y 4, same or different, are each CR d; X 1, X 2, and X 3, independently, are N or CR 3, wherein at least one of X 1, X 2, and X 3 is N; A is cycloalkyl, heterocycyl, aryl, or heteroaryl; L' is J-(CH 2) n -K, wherein n is an integer 3, 4, 5, 6, 7, 8, or 9, J-(CH 2) m -N(R 7)-(CH 2) p -K, wherein m and p, independently, are integers 0, 1, 2, 3, 4, 5, or 6, and R 7 is H, methyl, ethyl, propyl or butyl, (CH 2 O) l, (CH 2 CH 2 O) l, wherein l is 5,6, 7, 8, or 9, -(NHCHRC(=O)-) q, wherein R, independently, is an amino acid residue, and q is an integer 3, 4, 5, 6, 7, 8, or 9; J and K, independently, are (-C(=O)-, -C(=O)N-, -SO 2 -, or -CH 2 -; R 1 is hydrogen, a halo, cyano, C 1-6 alkyl, C 2-7 alkenyl, carbamoyl, or C 2-7 alkynyl optionally substituted with aC 1-4 acyl group; R 2 is C 1-6 alkyl optionally substituted with halo, OH, C 1-6 C(=O)R a, or CH 2 OC 1-6 alkyl; R 3 is hydrogen or C 1-6 alkyl; R 4 and R 5, independently are hydrogen or C 1-6 alkyl, or R 4 and R 5 are taken together with the carbon to which they are bound to form C 1-6 alkylene, C 1-6 heteroalkylene, C 2-6 alkenylene, or C 2-6 heteroalkenylene; R 6, independently, is cyano, halo, nitro, C 1-6 alkyl, haloC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, C 7-15 aralkyl, heteroaryl, heterocyclyl, -C R e, -C OR e, -C N(R e) 2, -C(NR e)N(R e) 2, -OR e, -OC R e, -OC OR e, -OC N(R e) 2, -OC(=NR e)N(R e) 2, -OS R e, -OS 2 R e, -OS N(R e) 2, -OS 2 N(R e) 2, -N(R e) 2, -NR e C R e, -NR e C N(R e) 2, -NR e C(=NR e)N(R e) 2, -NR e S R e, -NR e S 2 R e, -NR e S N(R e) 2, -NR e S 2 N(R e) 2, -SR e, -S R e, -S 2 R e, -S N(R e) 2, or -S 2 (NR e) 2, wherein q is 0, 1, 2, or 3; R a and R b, independently, are hydrogen, C 1-6 alkoxy, C 3-8 cycloalkyl, or a C 1-6 alkyl optionally substituted with a substituent selected from the group consisting of cyano, halo, hydroxy, C 1-6 alkoxy, and -N(R f) 2, or R a and R b are taken together with the nitrogen to which they are attached to form a heterocyclyl ring; R c is hydrogen, halo, C 1-6 alkyl, C 1-4 acyl, C 1-4 acyloxy, or -N(R g) 2; R d is hydrogen, halo, or C 1-6 alkyl; R e, independently, is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, C 7-15 aralkyl, heteroaryl, or heterocyclyl; R f, independently, is hydrogen or C 1-6 alkyl; and R g, independently, is hydrogen or C 1-4 acyl; or a pharmaceutically acceptable salt thereof. wherein Z is a heteroaryl group or R a R b NCO-; Y 1 and Y 2, independently, are N or CR c; Y 3 and Y 4, same or different, are each CR d; X 1, X 2, and X 3, independently, are N or CR 3, wherein at least one of X 1, X 2, and X 3 is N; A is cycloalkyl, heterocycyl, aryl, or heteroaryl; L' is J-(CH 2) n -K, wherein n is an integer 3, 4, 5, 6, 7, 8, or 9, J-(CH 2) m -N(R 7)-(CH 2) p -K, wherein m and p, independently, are integers 0, 1, 2, 3, 4, 5, or 6, and R 7 is H, methyl, ethyl, propyl or butyl, (CH 2 O) l, (CH 2 CH 2 O) l, wherein l is 5,6, 7, 8, or 9, -(NHCHRC(=O)-) q, wherein R, independently, is an amino acid residue, and q is an integer 3, 4, 5, 6, 7, 8, or 9; J and K, independently, are (-C(=O)-, -C(=O)N-, -SO 2 -, or -CH 2 -; R 1 is hydrogen, a halo, cyano, C 1-6 alkyl, C 2-7 alkenyl, carbamoyl, or C 2-7 alkynyl optionally substituted with aC 1-4 acyl group; R 2 is C 1-6 alkyl optionally substituted with halo, OH, C 1-6 C(=O)R a, or CH 2 OC 1-6 alkyl; R 3 is hydrogen or C 1-6 alkyl; R 4 and R 5, independently are hydrogen or C 1-6 alkyl, or R 4 and R 5 are taken together with the carbon to which they are bound to form C 1-6 alkylene, C 1-6 heteroalkylene, C 2-6 alkenylene, or C 2-6 heteroalkenylene; R 6, independently, is cyano, halo, nitro, C 1-6 alkyl, haloC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, C 7-15 aralkyl, heteroaryl, heterocyclyl, -C R e, -C OR e, -C N(R e) 2, -C(NR e)N(R e) 2, -OR e, -OC R e, -OC OR e, -OC N(R e) 2, -OC(=NR e)N(R e) 2, -OS R e, -OS 2 R e, -OS N(R e) 2, -OS 2 N(R e) 2, -N(R e) 2, -NR e C R e, -NR e C N(R e) 2, -NR e C(=NR e)N(R e) 2, -NR e S R e, -NR e S 2 R e, -NR e S N(R e) 2, -NR e S 2 N(R e) 2, -SR e, -S R e, -S 2 R e, -S N(R e) 2, or -S 2 (NR e) 2, wherein q is 0, 1, 2, or 3; R a and R b, independently, are hydrogen, C 1-6 alkoxy, C 3-8 cycloalkyl, or a C 1-6 alkyl optionally substituted with a substituent selected from the group consisting of cyano, halo, hydroxy, C 1-6 alkoxy, and -N(R f) 2, or R a and R b are taken together with the nitrogen to which they are attached to form a heterocyclyl ring; R c is hydrogen, halo, C 1-6 alkyl, C 1-4 acyl, C 1-4 acyloxy, or -N(R g) 2; R d is hydrogen, halo, or C 1-6 alkyl; R e, independently, is hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 6-14 aryl, C 7-15 aralkyl, heteroaryl, or heterocyclyl; R f, independently, is hydrogen or C 1-6 alkyl; and R g, independently, is hydrogen or C 1-4 acyl; or a pharmaceutically acceptable salt thereof.