A compound of Formula: or a pharmaceutically acceptable salt or isotopic derivative; wherein: A is CR 8 R 9 , C=O, C=S, C=CH 2 , SO 2 , S(O), P(O)Oalkyl, P(O)NHalkyl, P(O)N(alkyl) 2 , P(O)alkyl, P(O)OH, or P(O)NH 2 ; Z is O, S, CH 2 , CH(C 1 -C 4 alkyl), or C(C 1 -C 4 alkyl) 2 ; R 8 and R 9 are independently selected from hydrogen, alkyl, hydroxyl, alkoxy, amine, - NH(aliphatic), and -Nalkyl 2 ; or R 8 and R 9 form a 3-, 4-, 5-, or 6-membered spirocarbocycle, or a 4-, 5-, or 6-membered spiroheterocycle comprising 1 or 2 heteroatoms selected from N and O; Q 1 , Q 2 , Q 3 , and Q 4 are independently selected from CH, CR 12 , and N; and R 12 is independently selected from alkyl, alkenyl, alkynyl, halogen, hydroxyl, alkoxy, azide, amino, -C(O)H, -C(O)OH, -C(O)(aliphatic), -C(O)O(aliphatic), -NH(aliphatic), - N(aliphatic) 2 , -NHSO 2 (aliphatic), -N(aliphatic)SO 2 (aliphatic), -NHSO 2 (aryl or hetereoaryl), - N(aliphatic)SO 2 aryl, -NHSO 2 alkenyl, -N(alkyl)SO 2 alkenyl, -NHSO 2 alkynyl, - N(alkyl)SO 2 alkynyl, cyano, nitro, nitroso, -SH, -Salkyl, and haloalkyl, aliphatic, heteroaliphatic, aryl, heteroaryl and heterocyclic. or a pharmaceutically acceptable salt or isotopic derivative; wherein: A is CR 8 R 9 , C=O, C=S, C=CH 2 , SO 2 , S(O), P(O)Oalkyl, P(O)NHalkyl, P(O)N(alkyl) 2 , P(O)alkyl, P(O)OH, or P(O)NH 2 ; Z is O, S, CH 2 , CH(C 1 -C 4 alkyl), or C(C 1 -C 4 alkyl) 2 ; R 8 and R 9 are independently selected from hydrogen, alkyl, hydroxyl, alkoxy, amine, - NH(aliphatic), and -Nalkyl 2 ; or R 8 and R 9 form a 3-, 4-, 5-, or 6-membered spirocarbocycle, or a 4-, 5-, or 6-membered spiroheterocycle comprising 1 or 2 heteroatoms selected from N and O; Q 1 , Q 2 , Q 3 , and Q 4 are independently selected from CH, CR 12 , and N; and R 12 is independently selected from alkyl, alkenyl, alkynyl, halogen, hydroxyl, alkoxy, azide, amino, -C(O)H, -C(O)OH, -C(O)(aliphatic), -C(O)O(aliphatic), -NH(aliphatic), - N(aliphatic) 2 , -NHSO 2 (aliphatic), -N(aliphatic)SO 2 (aliphatic), -NHSO 2 (aryl or hetereoaryl), - N(aliphatic)SO 2 aryl, -NHSO 2 alkenyl, -N(alkyl)SO 2 alkenyl, -NHSO 2 alkynyl, - N(alkyl)SO 2 alkynyl, cyano, nitro, nitroso, -SH, -Salkyl, and haloalkyl, aliphatic, heteroaliphatic, aryl, heteroaryl and heterocyclic. A is CR 8 R 9 , C=O, C=S, C=CH 2 , SO 2 , S(O), P(O)Oalkyl, P(O)NHalkyl, P(O)N(alkyl) 2 , P(O)alkyl, P(O)OH, or P(O)NH 2 ; Z is O, S, CH 2 , CH(C 1 -C 4 alkyl), or C(C 1 -C 4 alkyl) 2 ; R 8 and R 9 are independently selected from hydrogen, alkyl, hydroxyl, alkoxy, amine, - NH(aliphatic), and -Nalkyl 2 ; or R 8 and R 9 form a 3-, 4-, 5-, or 6-membered spirocarbocycle, or a 4-, 5-, or 6-membered spiroheterocycle comprising 1 or 2 heteroatoms selected from N and O; Q 1 , Q 2 , Q 3 , and Q 4 are independently selected from CH, CR 12 , and N; and R 12 is independently selected from alkyl, alkenyl, alkynyl, halogen, hydroxyl, alkoxy, azide, amino, -C(O)H, -C(O)OH, -C(O)(aliphatic), -C(O)O(aliphatic), -NH(aliphatic), - N(aliphatic) 2 , -NHSO 2 (aliphatic), -N(aliphatic)SO 2 (aliphatic), -NHSO 2 (aryl or hetereoaryl), - N(aliphatic)SO 2 aryl, -NHSO 2 alkenyl, -N(alkyl)SO 2 alkenyl, -NHSO 2 alkynyl, - N(alkyl)SO 2 alkynyl, cyano, nitro, nitroso, -SH, -Salkyl, and haloalkyl, aliphatic, heteroaliphatic, aryl, heteroaryl and heterocyclic. <EOS>