A compound according to Formula I: wherein R 1 is hydrogen, hydroxy, halo, trifluoroalkyl, alkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, aralkyl, carboxyl, amido, amino, alkoxy, sulfanyl, sulfenyl, sulfonyl, or ether; R 2 is hydrogen, halo, hydroxy, trifluoromethyl, alkoxy, alkyl, alkenyl, alkynyl, carbocyclic, alkylcarbocyclic, alkylheterocyclic, heterocyclic, or -R 9 -OR 10, wherein R 9 is a covalent bond, or alkylene, and R 10 is hydrogen, alkyl, C-amido, or acyl; or R 2 together with R 3 and the atoms to which they are attached form a carbocyclic ring with 5 to 7 ring members or a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from oxygen or nitrogen; R 3 is hydrogen, hydroxy, halo, trifluoroalkyl, alkyl, alkoxy, sulfanyl, or -R 11 -OR 12, wherein R 11 is a covalent bond or alkylene, and R 12 is alkyl, C-amido, or acyl; or R 3 together with R 2 and the atoms to which they are attached form a carbocyclic ring with 5 to 7 ring members or a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from oxygen or nitrogen; or R 3 is absent when Y is =N-; R 4 is hydrogen, hydroxy, alkyl, arylalkoxy, carboxyl, -R 13 -O-R 14, or -R 13 -R 15; and wherein R 13 is a covalent bond or alkylene, and R 14 is hydrogen, C-amido, or acyl, or R 15 is N-amido, -POR 16 R 17, -SO 2 R 18, or sulfonamido, and wherein R 16, R 17, R 18 are independently alkoxy; R 5 is hydrogen, hydroxy, alkyl, arylalkoxy, alkenyl, alkynyl, aryl, or aralkyl; R 6 is hydrogen, hydroxy, sulfanyl, alkyl, alkenyl, alkynyl, aryl, arylalkyl, alkoxy, aryloxy, arylalkoxy, or a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from oxygen or nitrogen; R 7 is hydrogen, hydroxy, arylalkoxy, alkyl, acyl, carboxyl, or absent; R 8 is hydrogen, hydroxy, or arylalkoxy; X 1 is -CHR 19 - or -CR 19 =, and wherein R 19 is selected from hydrogen, halo, alkyl, alkenyl, or alkynyl; or X 1 together with X 2 form a carbocyclic ring having 3 to 7 ring members; or wherein X 1 -X 2 is -C≡C-; X 2 is -CHR 20 - or =CR 20 -, and wherein R 20 is selected from hydrogen, halo, alkyl, alkenyl, or alkynyl; or X 2 together with X 1 form a carbocyclic ring having 3 to 7 ring members; or wherein X 1 -X 2 is -C≡C-; X 3 is O or CH 2; X is =CR 21 - or =N-, wherein R 21 is hydrogen, halo, trifluoromethyl, alkyl, alkenyl, alkynyl, alkoxy, or hydroxy; R' is H or alkyl; R" is alkyl, alkoxy, haloalkyl, alkylcycloalkyl, or alkylamidoalkyl; Y is =CR 3 - or =N-; Z is CH, or Z-Z 1 is -C=C-; Z 1 is CH, O, S, N, or Z-Z 1 is -C=C-; and n is 0, 1, 2, or 3; or a pharmaceutically acceptable salt thereof. R 1 is hydrogen, hydroxy, halo, trifluoroalkyl, alkyl, alkenyl, alkynyl, carbocyclic, heterocyclic, aryl, aralkyl, carboxyl, amido, amino, alkoxy, sulfanyl, sulfenyl, sulfonyl, or ether; R 2 is hydrogen, halo, hydroxy, trifluoromethyl, alkoxy, alkyl, alkenyl, alkynyl, carbocyclic, alkylcarbocyclic, alkylheterocyclic, heterocyclic, or -R 9 -OR 10, wherein R 9 is a covalent bond, or alkylene, and R 10 is hydrogen, alkyl, C-amido, or acyl; or R 9 is a covalent bond, or alkylene, and R 10 is hydrogen, alkyl, C-amido, or acyl; or R 2 together with R 3 and the atoms to which they are attached form a carbocyclic ring with 5 to 7 ring members or a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from oxygen or nitrogen; R 3 is hydrogen, hydroxy, halo, trifluoroalkyl, alkyl, alkoxy, sulfanyl, or -R 11 -OR 12, wherein R 11 is a covalent bond or alkylene, and R 12 is alkyl, C-amido, or acyl; or R 11 is a covalent bond or alkylene, and R 12 is alkyl, C-amido, or acyl; or R 3 together with R 2 and the atoms to which they are attached form a carbocyclic ring with 5 to 7 ring members or a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from oxygen or nitrogen; or R 3 is absent when Y is =N-; R 4 is hydrogen, hydroxy, alkyl, arylalkoxy, carboxyl, -R 13 -O-R 14, or -R 13 -R 15; and wherein R 13 is a covalent bond or alkylene, and R 14 is hydrogen, C-amido, or acyl, or R 15 is N-amido, -POR 16 R 17, -SO 2 R 18, or sulfonamido, and wherein R 16, R 17, R 18 are independently alkoxy; R 13 is a covalent bond or alkylene, and R 14 is hydrogen, C-amido, or acyl, or R 15 is N-amido, -POR 16 R 17, -SO 2 R 18, or sulfonamido, and wherein R 16, R 17, R 18 are independently alkoxy; R 5 is hydrogen, hydroxy, alkyl, arylalkoxy, alkenyl, alkynyl, aryl, or aralkyl; R 6 is hydrogen, hydroxy, sulfanyl, alkyl, alkenyl, alkynyl, aryl, arylalkyl, alkoxy, aryloxy, arylalkoxy, or a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from oxygen or nitrogen; R 7 is hydrogen, hydroxy, arylalkoxy, alkyl, acyl, carboxyl, or absent; R 8 is hydrogen, hydroxy, or arylalkoxy; X 1 is -CHR 19 - or -CR 19 =, and wherein R 19 is selected from hydrogen, halo, alkyl, alkenyl, or alkynyl; or X 1 together with X 2 form a carbocyclic ring having 3 to 7 ring members; or wherein X 1 -X 2 is -C≡C-; X 2 is -CHR 20 - or =CR 20 -, and wherein R 20 is selected from hydrogen, halo, alkyl, alkenyl, or alkynyl; or X 2 together with X 1 form a carbocyclic ring having 3 to 7 ring members; or wherein X 1 -X 2 is -C≡C-; X 3 is O or CH 2; X is =CR 21 - or =N-, wherein R 21 is hydrogen, halo, trifluoromethyl, alkyl, alkenyl, alkynyl, alkoxy, or hydroxy; R' is H or alkyl; R" is alkyl, alkoxy, haloalkyl, alkylcycloalkyl, or alkylamidoalkyl; Y is =CR 3 - or =N-; Z is CH, or Z-Z 1 is -C=C-; Z 1 is CH, O, S, N, or Z-Z 1 is -C=C-; and n is 0, 1, 2, or 3;