A compound chosen from compounds of Formula 1: and pharmaceutically acceptable salts, solvates, chelates, non-covalent complexes, and mixtures thereof, wherein R is chosen from aryl, heteroaryl and in which; aryl encompasses 5- and 6-membered carbocyclic aromatic rings; bicyclic ring systems wherein at least one ring is carbocyclic and aromatic; and tricyclic ring systems wherein at least one ring is carbocyclic and aromatic; and wherein aryl includes 5- and 6-membered carbocyclic aromatic rings fused to a 5- to 7-membered heterocycloalkyl ring containing 1 or more heteroatoms chosen from N, O, and S; hetero-aryl encompasses 5- to 7-membered aromatic, monocyclic rings containing one or more heteroatoms chosen from N, O, and S, with the remaining ring atoms being carbon; and bicyclic heterocycloalkyl rings containing one or more heteroatoms chosen from N, O, and S, with the remaining ring atoms being carbon and wherein at least one heteroatom is present in an aromatic ring; and wherein heteroaryl includes a 5- to 7-membered heterocycloalkyl, aromatic ring fused to a 5- to 7-membered cycloalkyl ring; R 5 is chosen from hydrogen, hydroxy, alkyl groups having one to four carbons, sulfonyl, amino, alkoxy groups having one to four carbons, alkyl groups having one to four carbons substituted with one or more halo, alkoxy groups having one to four carbons substituted with one or more halo, alkyl groups having one to four carbons substituted with hydroxy, heterocycloalkyl, and heteroaryl; and X is chosen from N and CH; R 4 is chosen from hydrogen, alkyl groups having one to four carbons, alkoxy groups having one to four carbons, halo, and hydroxy; R 21 and R 22 are independently chosen from hydrogen and alkyl groups having one to four carbons; R 16 is chosen from hydrogen, cyano, cycloalkyl, and alkyl groups having one to four carbons; and alkyl groups having one to four carbons substituted with a group chosen from alkoxy, amino, and acyl; L is chosen from C 0 -C 4 alkylene, -O- C 0 -C 4 alkylene, -(C 0 -C 4 alkylene) -, -(C 0 -C 4 alkylene)(SO 2)-; and -(C 0 -C 4 alkylene)(C=O)-; and G is chosen from hydrogen, halo, hydroxy, alkoxy, nitro, alkyl, -NR 7 R 8 wherein R 7 and R 8 are independently chosen from hydrogen, acyl, and (C 1 -C 6)alkyl; or wherein R 7 and R 8, together with the nitrogen to which they are bound, form a 5- to 7-membered nitrogen containing heterocycloalkyl which optionally further includes one or two additional heteroatoms chosen from N, O, and S, carbamimidoyl, heterocycloalkyl, cycloalkyl, aryl, heteroaryl, 4-acyl-piperazin-1-yl, 4-alkyl groups having one to four carbons-piperazin-1-yl, 4-alkyl groups having one to four carbons-piperidin-1-yl, 4-hydroxy-4-alkyl groups having one to four carbons-piperidin-1-yl, 3-oxo-piperazin-1-yl, 4-alkyl groups having one to four carbons-homopiperazin-1-yl. R is chosen from aryl, heteroaryl and aryl encompasses 5- and 6-membered carbocyclic aromatic rings; bicyclic ring systems wherein at least one ring is carbocyclic and aromatic; and tricyclic ring systems wherein at least one ring is carbocyclic and aromatic; and wherein aryl includes 5- and 6-membered carbocyclic aromatic rings fused to a 5- to 7-membered heterocycloalkyl ring containing 1 or more heteroatoms chosen from N, O, and S; hetero-aryl encompasses 5- to 7-membered aromatic, monocyclic rings containing one or more heteroatoms chosen from N, O, and S, with the remaining ring atoms being carbon; and bicyclic heterocycloalkyl rings containing one or more heteroatoms chosen from N, O, and S, with the remaining ring atoms being carbon and wherein at least one heteroatom is present in an aromatic ring; and wherein heteroaryl includes a 5- to 7-membered heterocycloalkyl, aromatic ring fused to a 5- to 7-membered cycloalkyl ring; R 5 is chosen from hydrogen, hydroxy, alkyl groups having one to four carbons, sulfonyl, amino, alkoxy groups having one to four carbons, alkyl groups having one to four carbons substituted with one or more halo, alkoxy groups having one to four carbons substituted with one or more halo, alkyl groups having one to four carbons substituted with hydroxy, heterocycloalkyl, and heteroaryl; and X is chosen from N and CH; R 4 is chosen from hydrogen, alkyl groups having one to four carbons, alkoxy groups having one to four carbons, halo, and hydroxy; R 21 and R 22 are independently chosen from hydrogen and alkyl groups having one to four carbons; R 16 is chosen from hydrogen, cyano, cycloalkyl, and alkyl groups having one to four carbons; and alkyl groups having one to four carbons substituted with a group chosen from alkoxy, amino, and acyl; L is chosen from C 0 -C 4 alkylene, -O- C 0 -C 4 alkylene, -(C 0 -C 4 alkylene) -, -(C 0 -C 4 alkylene)(SO 2)-; and -(C 0 -C 4 alkylene)(C=O)-; and G is chosen from hydrogen, halo, hydroxy, alkoxy, nitro, alkyl, -NR 7 R 8 wherein R 7 and R 8 are independently chosen from hydrogen, acyl, and (C 1 -C 6)alkyl; or wherein R 7 and R 8, together with the nitrogen to which they are bound, form a 5- to 7-membered nitrogen containing heterocycloalkyl which optionally further includes one or two additional heteroatoms chosen from N, O, and S, carbamimidoyl, heterocycloalkyl, cycloalkyl, aryl, heteroaryl, 4-acyl-piperazin-1-yl, 4-alkyl groups having one to four carbons-piperazin-1-yl, 4-alkyl groups having one to four carbons-piperidin-1-yl, 4-hydroxy-4-alkyl groups having one to four carbons-piperidin-1-yl, 3-oxo-piperazin-1-yl, 4-alkyl groups having one to four carbons-homopiperazin-1-yl.