RU2004111295A - NEW LIGANDS FOR HISB10ZN2 + HEXAMER INSULIN SITES IN R-STATE - Google Patents

Claims (204)

1. Zinc-binding ligand of the following General formula (III)

where A represents a chemical group that reversibly binds to His ^B10 Zn ²⁺ site of the insulin hexamer; B is a linker selected from valence bond chemical group G ^{B of the} formula -B ¹ -B ² -C (O) -, -B ¹ -B ² -SO ₂ -, -B ¹ -B ² -CH ₂ - or –B ¹ -B ² -NH-, where In ¹ represents a valence bond, -O-, -S- or -NR ⁶ -, B ² represents a valence bond, C ₁ -C ₁₈ -alkylene, C ₂ -C ₁₈ -alkenylene, C ₂ -C ₁₈ -alkynylene, arylene, heteroarylene, -C ₁ -C ₁₈ -alkylaryl, -C ₂ -C _18- alkenylaryl-, -C ₂ -C ₁₈ -alkynylaryl-, -C (= O) -C ₁ -C ₁₈ -alkyl-C (= O) -, -C (= O) -C ₁ -C ₁₈ - alkenyl-C (= O) -, -C (= O) -C ₁ -C ₁₈ -alkyl-O-C ₁ -C ₁₈ -alkyl-C (= O) -, -C (= O) -C ₁ -C ₁₈ -alkyl-S-C ₁ -C ₁₈ -alkyl-C (= O) -, -C (= O) -C ₁ -C ₁₈ -alkyl-NR ⁶ -C ₁ -C ₁₈ -alkyl-C (= O) -, -C (= O) -aryl-C (= O) -, -C (= O) -heteroaryl-C (= O) -, where the fragments of alkylene, alkenylene and alkynylene are optionally substituted with —CN, —CF ₃ , —OCF ₃ , —OR ⁶ or –NR ⁶ R ⁷ , and the fragments of arylene and heteroarylene are optionally substituted with halogen, —C (O) OR ⁶ , —C ( O) H, OCOR ⁶ , -SO ₂ , -CN, -CF ₃ , -OCF ₃ , -NO ₂ , -OR ⁶ , -NR ⁶ R ⁷ , C ₁ -C ₁₈ alkyl or C ₁ -C ₁₈ - alkanoyl; R ⁶ and R ⁷ independently represent H, C ₁ -C ₄ alkyl; C is a fragment consisting of 0-5 neutral amino acids, where the individual neutral amino acids are the same or different; D is a fragment comprising 1-20 positively charged groups independently selected from amino or guanidino groups, where the individual positively charged groups are the same or different; and X represents —OH, —NH _2, or a diamino group, or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers, including a racemic mixture or any tautomeric forms. 2. The zinc-binding ligand according to claim 1, where A is a chemical structure selected from the group consisting of carboxylates, dithiocarboxylates, phenolates, thiophenolates, alkylthiolates, sulfonamides, imidazoles, triazoles, 4-cyano-1,2,3-triazoles, benzimidazoles, benzotriazoles, purines, thiazolidinediones, tetrazoles, 5-mercaptotetrazoles, rhodanines, N-hydroxyazoles, hydantoins, thiohydantoins, barbiturates, naphthoic acids and salicylic acids. 3. The zinc binding ligand according to claim 2, wherein A is a chemical structure selected from the group consisting of benzotriazoles, 3-hydroxy-2-naphthoic acids, salicylic acids, tetrazoles, thiazolidinediones, 5-mercaptotetrazoles or 4-cyano-1, 2,3-triazoles. 4. Zinc-binding ligand according to any one of claims 1 to 3, where A represents

or

where X represents = O, = S or = NH; Y represents —S—, —O— or —NH—; R ⁸ and R ¹¹ independently represent hydrogen or C ₁ -C ₆ alkyl; R ⁹ represents hydrogen or C ₁ -C ₆ alkyl or aryl, R ⁸ and R ⁹ may optionally combine to form a double bond; R ¹⁰ and R ¹² independently represent hydrogen, aryl, C ₁ -C ₆ alkyl or —C (O) NR ¹⁶ R ¹⁷ ; E and G independently are C ₁ -C ₆ alkylene, arylene, -aryl-C ₁ -C ₆ -alkyl-, aryl-C ₂ -C ₆ -alkylene- or heteroarylene, where alkylene or alkenylene is optionally substituted with one or more substituents independently selected from halogen, —CN, —CF ₃ , —OCF ₃ , aryl, —COOH and –NH ₂ , and arylene or heteroarylene are optionally substituted with up to four substituents R ¹³ , R ¹⁴ , R ¹⁵ and R ^15A ; E and R ¹⁰ may be joined by one or two valence bonds, G and R ¹² may be joined by one or two valence bonds; R ¹³ , R ¹⁴ , R ¹⁵ and R ^{15A are} independently selected from hydrogen, halogen, —CN, —CH ₂ CN, —CHF ₂ , —CF ₃ , —OCF ₃ , —OCHF ₂ , —OCH ₂ CF ₃ , —OCF ₂ CHF ₂ , -S (O) ₂ CF ₃ , -OS (O) ₂ CF ₃ , -SCF ₃ , -NO ₂ , -OR ¹⁶ , -NR ¹⁶ R ¹⁷ , -SR ¹⁶ , -NR ¹⁶ S (O ) ₂ R ¹⁷ , -S (O) ₂ NR ¹⁶ R ¹⁷ , -S (O) NR ¹⁶ R ¹⁷ , -S (O) R ¹⁶ , -S (O) ₂ R ¹⁶ , -OS (O) ₂ R ¹⁶ , -C (O) NR ¹⁶ R ¹⁷ , -OC (O) NR ¹⁶ R ¹⁷ , -NR ¹⁶ C (O) R ¹⁷ , -CH ₂ C (O) NR ^l6 R ¹⁷ , -OC ₁ -C ₆ -alkyl-C (O) ONR ¹⁶ R ¹⁷ , -CH ₂ OR ¹⁶ , -CH ₂ OC (O) R ¹⁶ , -CH ₂ NR ¹⁶ R ¹⁷ , -OC (O) R ¹⁶ , -OC ₁ -C ₆ -alkyl-C (O) OR ¹⁶ , -OC ₁ -C ₆ -alkyl-OR ¹⁶ , -SC ₁ -C ₆ -alkyl-C (O) OR ¹⁶ , -C ₂ -C ₆ -alkenyl-C (= O) OR ¹⁶ , -NR ¹⁶ -C (= O) -C ₁ -C ₆ -alkyl-C (= O) OR ¹⁶ , -NR ¹⁶ -C (= O) -C ₁ -C ₆ -alkenyl-C (= O) OR ¹⁶ , —C (O) OR ¹⁶ or —C ₂ -C ₆ alkenyl-C (= O) R ¹⁶ , = O or —C ₂ -C ₆ alkenyl-C (= O) - NR ¹⁶ R ¹⁷ , C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl or C ₂ -C ₆ alkynyl, which may optionally be substituted with one or more substituents selected from halogen, —CN, —CF ₃ , —OCF ₃ , —OR ¹⁶ and —NR ¹⁶ R ¹⁷ , aryl, aryloxy, aryloxycarbonyl, aroyl, arylsulfanyl, aryl-C ₁ -C ₆ alkoxy, aryl-C ₁ -C ₆ -alkyl, aryl-C ₂ -C ₆ alkenyl, aroyl-C ₂ -C ₆ alkenyl, aryl-C ₂ -C ₆ - alkynyl, heteroaryl, heteroaryl-C ₁ -C ₆ -alkyl, heteroaryl-C ₂ -C ₆ -alkenyl or heteroaryl-C ₂ -C ₆ -alkynyl, cyclic fragments of which may optionally be substituted with one or more substituents selected from halogen, -C (O) OR ¹⁶ , -CH ₂ C (O) OR ¹⁶ , -CH ₂ OR ¹⁶ , —CN, —CF ₃ , —OCF ₃ , —NO ₂ , —OR ¹⁶ , —NR ¹⁶ R ¹⁷ , S (O) ₂ R ¹⁶ , aryl, and C ₁ -C ₆ alkyl; R ¹⁶ and R ¹⁷ independently represent hydrogen, OH, C ₁ -C ₂₀ -alkyl, aryl-C ₁ -C ₆ -alkyl or aryl, where the alkyl groups may optionally be substituted with one or more substituents selected from halogen, -CN , -CF ₃ , -OCF ₃ , -OC ₁ -C ₆ -alkyl, -C (O) OC ₁ -C ₆ -alkyl, -COOH and -NH ₂ , and aryl groups may optionally be substituted with halogen, -C ( O) OC ₁ —C ₆ alkyl, —COOH, —CN, —CF ₃ , —OCF ₃ , —NO ₂ , —OH, —OC ₁ —C ₆ alkyl, —NH ₂ , C (= O) or C ₁ -C ₆ alkyl; R ¹⁶ and R ¹⁷ , when attached to the same nitrogen atom, can form a 3-8 membered heterocyclic ring with the indicated nitrogen atom, the heterocyclic ring optionally includes one or two additional heteroatoms selected from nitrogen, oxygen and sulfur, and optionally contains one or two double bonds. 5. The zinc-binding ligand according to claim 4, where X represents = O or = S. 6. The zinc-binding ligand according to claim 5, where X represents = O. 7. The zinc-binding ligand according to claim 5, where X represents = S. 8. The zinc binding ligand of claim 4, wherein Y is —O — or —S—. 9. The zinc binding ligand of claim 8, wherein Y is —O—. 10. The zinc binding ligand of claim 8, wherein Y is —S—. 11. The zinc binding ligand according to claim 4, wherein E is arylene optionally substituted with up to four substituents R ¹³ , R ¹⁴ , R ¹⁵ and R ^15A . 12. The zinc binding ligand according to claim 11, wherein E is phenylene or naphthylene, optionally substituted with up to four substituents R ¹³ , R ¹⁴ , R ¹⁵ and R ^15A . 13. Zinc-binding ligand according to item 12, where E represents

or

14. Zinc-binding ligand according to item 13, where E represents

or

15. The zinc-binding ligand according to claim 12, wherein E is phenylene. 16. The zinc-binding ligand according to claim 4, where E is heteroarylene, optionally substituted with up to four substituents R ¹³ , R ¹⁴ , R ¹⁵ and R ^15A . 17. The zinc binding ligand of claim 16, wherein E is benzofuranilidene optionally substituted with up to four substituents R ¹³ , R ¹⁴ , R ¹⁵ and R ^15A . 18. Zinc-binding ligand according to 17, where E represents

19. The zinc binding ligand of claim 16, wherein E is carbazolylidene optionally substituted with up to four substituents R ¹³ , R ¹⁴ , R ¹⁵ and R ^15A . 20. The zinc-binding ligand according to claim 19, where E represents

21. The zinc binding ligand of claim 16, wherein E is quinolylidene optionally substituted with up to four substituents R ¹³ , R ¹⁴ , R ¹⁵ and R ^15A . 22. Zinc-binding ligand according to item 21, where E represents

or

23. The zinc binding ligand of claim 16, wherein E is indolylene optionally substituted with up to four substituents R ¹³ , R ¹⁴ , R ¹⁵ and R ^15A . 24. Zinc-binding ligand according to item 23, where E represents

25. The zinc binding ligand according to claim 4, wherein R ⁸ is hydrogen. 26. The zinc binding ligand according to claim 4, wherein R ⁹ is hydrogen. 27. The zinc binding ligand according to claim 4, wherein R ⁸ and R ^{9 are} connected to form a double bond. 28. The zinc binding ligand according to claim 4, wherein R ¹⁰ is C ₁ -C ₆ alkyl. 29. The zinc binding ligand of claim 28, wherein R ¹⁰ is methyl. 30. The zinc binding ligand according to claim 4, wherein G is phenylene optionally substituted with up to four substituents R ¹³ , R ¹⁴ , R ¹⁵ and R ^15A . 31. The zinc binding ligand according to claim 4, wherein R ¹¹ is hydrogen. 32. The zinc binding ligand according to claim 4, wherein R ¹² is hydrogen. 33. The zinc binding ligand according to claim 4, where R ¹³ , R ¹⁴ , R ¹⁵ and R ^{15A are} independently selected from hydrogen, halogen, —NO ₂ , —OR ⁶ , —NR ¹⁶ R ¹⁷ , —SR ¹⁶ , —NR ¹⁶ S (O) ₂ R ¹⁷ , -S (O) ₂ NR ¹⁶ R ¹⁷ , -S (O) NR ¹⁶ R ¹⁷ , -S (O) R ¹⁶ , -S (O) ₂ R ¹⁶ , -OS (O) ₂ R ¹⁶ , -NR ¹⁶ C (O) R ¹⁷ , -CH ₂ OR ¹⁶ , -CH ₂ OS (O) R ¹⁶ , -CH ₂ NR ¹⁶ R ¹⁷ , -OC (O) R ¹⁶ , -OC ₁ - C ₆ -alkyl-C (O) OR ¹⁶ , -OC ₁ -C ₆ -alkyl-C (O) NR ¹⁶ R ¹⁷ , -OC ₁ -C ₆ -alkyl-OR ¹⁶ , -SC ₁ -C ₆ -alkyl -C (O) OR ¹⁶ , -C ₂ -C ₆ alkenyl-C (= O) OR ¹⁶ , -C (O) OR ¹⁶ or-C ₂ -C ₆ alkenyl-C (= O) R ¹⁶ , C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl or C ₂ -C ₆ alkynyl, which may optionally be substituted with one or more substituents selected from halogen, —CN, —CF ₃ , —OCF ₃ , - OR ¹⁶ and –NR ¹⁶ R ¹⁷ , aryl, arylok si, aroyl, arylsulfanyl, aryl-C ₁ -C ₆ -alkoxy, aryl-C ₁ -C ₆ -alkyl, aryl-C ₂ -C ₆ -alkenyl, aroyl-C ₂ -C ₆ -alkenyl, aryl-C ₂ -C ₆ -alkynyl, heteroaryl, heteroaryl-C ₁ -C ₆ -alkyl, the cyclic fragments of which may optionally be substituted with one or more substituents selected from halogen, -C (O) OR ¹⁶ , -CH ₂ C (O) OR ¹⁶ , —CH ₂ OR ¹⁶ , —CN, —CF ₃ , —OCF ₃ , —NO ₂ , —OR ¹⁶ , —NR ¹⁶ R ^17, and C ₁ -C ₆ alkyl. 34. The zinc binding ligand according to claim 33, wherein R ¹³ , R ¹⁴ , R ¹⁵ and R ^{15A are} independently selected from hydrogen, halogen, —NO ₂ , —OR ⁶ , —NR ¹⁶ R ¹⁷ , —SR ¹⁶ , —S (O ) ₂ R ¹⁶ , -OS (O) ₂ R ¹⁶ , -CH ₂ OC (O) R ¹⁶ , -OC (O) R ¹⁶ , -OC ₁ -C ₆ -alkyl-C (O) OR ¹⁶ , -OC ₁ -C ₆ -alkyl-OR ¹⁶ , -SC ₁ -C ₆ -alkyl-C (O) OR ¹⁶ , -C (O) OR ¹⁶ or -C ₂ -C ₆ -alkenyl-C (= O) R ¹⁶ , C ₁ -C ₆ alkyl or C ₁ -C ₆ alkenyl, which may optionally be substituted with one or more substituents selected from halogen, —CN, —CF ₃ , —OCF ₃ , —OR ¹⁶ and —NR ¹⁶ R ¹⁷ , aryl, aryloxy, aroyl, aryl-C ₁ -C ₆ -alkoxy, aryl-C ₁ -C ₆ -alkyl, heteroaryl, cyclic fragments of which may optionally be substituted with one or more substituents selected from halogen, —C (O) OR ¹⁶ , —CH ₂ C (O) OR ¹⁶ , —CH ₂ OR ¹⁶ , —CN, —CF ₃ , —OCF ₃ , —NO ₂ , —OR ¹⁶ , —NR ¹⁶ R ^17, and C ₁ -C ₆ alkyl. 35. The zinc binding ligand according to claim 34, wherein R ¹³ , R ¹⁴ , R ¹⁵ and R ^{15A are} independently selected from hydrogen, halogen, —NO ₂ , —OR ⁶ , —NR ¹⁶ R ¹⁷ , —SR ¹⁶ , —S (O ) ₂ R ¹⁶ , -OS (O) ₂ R ¹⁶ , -CH ₂ OC (O) R ¹⁶ , -OC (O) R ¹⁶ , -OC ₁ -C ₆ -alkyl-C (O) OR ¹⁶ , -OC ₁ -C ₆ -alkyl-OR ¹⁶ , -SC ₁ -C ₆ -alkyl-C (O) OR ¹⁶ , -C (O) OR ¹⁶ or -C ₂ -C ₆ -alkenyl-C (= O) R ¹⁶ , C ₁ -C ₆ alkyl or C ₁ -C ₆ alkenyl, which may optionally be substituted with one or more substituents selected from halogen, —CF ₃ , —OR ¹⁶ and —NR ¹⁶ R ¹⁷ , aryl, aryloxy, aroyl aryl-C ₁ -C ₆ alkoxy, aryl-C ₁ -C ₆ -alkyl, heteroaryl, cyclic moieties of which may optionally be substituted with one or more substituents selected from halogen, C (O) OR ¹⁶ , —CN, —NO ₂ , —OR ¹⁶ , —NR ¹⁶ R ^17, and C ₁ -C ₆ alkyl. 36. The zinc binding ligand according to claim 35, wherein R ¹³ , R ¹⁴ , R ^15, and R ^{15A are} independently selected from hydrogen, halogen, —OR ⁶ , —OC ₁ —C ₆ -alkyl-C (O) OR ¹⁶ or —C (O) OR ¹⁶ , C ₁ -C ₆ alkyl, which may optionally be substituted with one or more substituents selected from halogen, -OR ¹⁶ and –NR ¹⁶ R ¹⁷ , aryl, aryloxy, aryl-C ₁ -C ₆ - alkoxy, cyclic fragments of which may optionally be substituted with one or more substituents selected from halogen, C (O) OR ¹⁶ , OR ¹⁶ and C ₁ -C ₆ alkyl. 37. The zinc binding ligand according to claim 4, wherein R ¹⁶ and R ^{17 are} independently hydrogen, C ₁ -C ₂₀ alkyl or aryl, where the alkyl groups may optionally be substituted with one or more substituents selected from halogen, —CF ₃ , —OCF ₃ , —OC ₁ —C ₆ -alkyl, —COOH and —NH ₂ , and the aryl groups may optionally be substituted with halogen, —COOH, —CN, —CF ₃ , —OCF ₃ , —NO ₂ , —OH, -OC ₁ -C ₆ -alkyl, -NH ₂ , C (= O) or C ₁ -C ₆ -alkyl; R ¹⁶ and R ¹⁷ , when attached to the same nitrogen atom, can form a 3-8 membered heterocyclic ring with the indicated nitrogen atom, the heterocyclic ring optionally includes one or two additional heteroatoms selected from nitrogen, oxygen and sulfur and optionally contains one or two double bonds. 38. The zinc binding ligand of claim 37, wherein R ¹⁶ and R ^{17 are} independently hydrogen, C ₁ -C ₂₀ alkyl, or aryl, where the alkyl groups may optionally be substituted with one or more substituents selected from halogen, —CF ₃ , —OC ₁ —C ₆ -alkyl, —COOH and —NH ₂ and aryl groups may optionally be substituted with halogen, —COOH, —CN, —CF ₃ , —OCF ₃ , —OH, —NH _2, or C ₁ —C _6- alkyl. 39. Zinc-binding ligand according to any one of claims 1 to 3, where A represents

or

or

where R ²⁰ represents hydrogen or C ₁ -C ₆ alkyl; R ²¹ represents hydrogen or C ₁ -C ₆ alkyl; U and V are a valence bond or C ₁ -C ₆ alkylene optionally substituted with one or more hydroxy, C ₁ -C ₆ alkyl or independently aryl; J represents C ₁ -C ₆ alkylene, arylene or heteroarylene, wherein arylene or heteroarylene is optionally substituted with R ²² , R ²³ and R ²⁴ in an amount of up to three; L is C ₁ -C ₆ alkylene, arylene or heteroarylene, wherein arylene or heteroarylene is optionally substituted with up to three substituents R ²⁵ , R ²⁶ and R ²⁷ ; R ¹⁸ , R ¹⁹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ²⁶ and R ^{27 are} independently selected from hydrogen, halogen, —CN, —CH ₂ CN, —CHF ₂ , —CF ₃ , —OCF ₃ , -OCHF ₂ , -OCH ₂ CF ₃ , -OCF ₂ CHF ₂ , -S (O) ₂ CF ₃ , -SCF ₃ , -NO ₂ , -OR ²⁸ , -NR ²⁸ R ²⁹ , -SR ²⁸ , -NR ²⁸ S (O) ₂ R ²⁹ , -S (O) ₂ NR ²⁸ R ²⁹ , -S (O) NR ²⁸ R ²⁹ , -S (O) R ²⁸ , -S (O) ₂ R ²⁸ , -C (O ) NR ²⁸ R ²⁹ , -OC (O) NR ²⁸ R ²⁹ , -NR ²⁸ C (O) R ²⁹ , -NR ²⁸ C (O) OR ²⁹ , -CH ₂ C (O) NR ²⁸ R ²⁹ , -OCH ₂ C (O) NR ²⁸ R ²⁹ , -CH ₂ OR ²⁸ , -CH ₂ NR ²⁸ R ²⁹ , -OC (O) R ²⁸ , -OC ₁ -C ₆ -alkyl-C (O) OR ²⁸ , -SC ₁ -C ₆ -alkyl-C (O) OR ²⁸ , -C ₂ -C ₆ -alkenyl-C (= O) OR ²⁸ , -NR ²⁸ -C (= O) -C ₁ -C ₆ -alkyl-C (= O) OR ²⁸ , -NR ²⁸ -C (= O) -C ₁ -C ₆ alkenyl-C (= O) OR ²⁸ , -C (= O) NR ²⁸ -C ₁ -C ₆ -alkyl- C (= O) OR ²⁸ , -C ₁ -C ₆ -alkyl-C (= O) OR ²⁸ or -C (O) OR ²⁸ , C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl or C C ₂ -C ₆ -alkynyl, which may be neobyazate no substituted with one or more substituents selected from halogen, -CN, -CF _3, -OCF _3, -OR ²⁸ and -NR ²⁸ R ^29, aryl, aryloxy, aryloxycarbonyl, aroyl, aryl-C ₁ -C ₆ alkoxy, aryl-C ₁ -C ₆ -alkyl, aryl-C ₂ -C ₆ -alkenyl, aryl-C ₂ -C ₆ -alkynyl, heteroaryl, heteroaryl-C ₁ -C ₆ -alkyl, heteroaryl-C ₂ -C ₆ - alkenyl or heteroaryl-C ₂ -C ₆ alkynyl, the cyclic fragments of which may optionally be substituted with one or more substituents selected from halogen, —C (O) OR ²⁸ , —CN, —CF ₃ , —OCF ₃ , —NO ₂ , -OR ²⁸ , -NR ²⁸ R ²⁹ and C ₁ -C ₆ alkyl; R ²⁸ and R ²⁹ independently represent hydrogen, C ₁ -C ₆ alkyl, aryl-C ₁ -C ₆ alkyl or aryl, or R ²⁸ and R ²⁹ when attached to the same nitrogen atom, together with the specified a nitrogen atom can form a 3-8 membered heterocyclic ring, optionally containing one or two additional heteroatoms selected from nitrogen, oxygen and sulfur, and optionally containing one or two double bonds. 40. The zinc binding ligand according to claim 39, wherein U is a valence bond. 41. The zinc binding ligand according to claim 39, wherein U is C ₁ -C ₆ alkylene optionally substituted with one or more hydroxy, C ₁ -C ₆ alkyl or aryl. 42. The zinc binding ligand of claim 39, wherein J is arylene or heteroarylene, wherein arylene or heteroarylene is optionally substituted with substituents R ²² , R ²³ and R ²⁴ , in an amount of up to three. 43. The zinc binding ligand according to claim 42, wherein J is arylene optionally substituted with substituents R ²² , R ²³ and R ²⁴ , in an amount of up to three. 44. The zinc binding ligand according to claim 43, wherein J is phenylene, optionally substituted with substituents R ²² , R ²³ and R ²⁴ , in an amount of up to three. 45. Zinc-binding ligand according to item 44, where J represents

46. The zinc binding ligand according to claim 39, wherein R ²² , R ²³ and R ^{24 are} independently selected from hydrogen, halogen, —CHF ₂ , —CF ₃ , —OCF ₃ , —OCHF ₂ , —OCH ₂ CF ₃ , —OCF ₂ CHF ₂ , -SCF ₃ , -NO ₂ , -OR ²⁸ , -NR ²⁸ R ²⁹ , -SR ²⁸ , -C (O) NR ²⁸ R ²⁹ , -OC (O) NR ²⁸ R ²⁹ , -NR ²⁸ C ( O) R ²⁹ , -NR ²⁸ C (O) OR ²⁹ , -CH ₂ C (O) NR ²⁸ R ²⁹ , -OCH ₂ C (O) NR ²⁸ R ²⁹ , -CH ₂ OR ²⁸ , -CH ₂ NR ²⁸ R ²⁹ , -OC (O) R ²⁸ , -OC ₁ -C ₆ -alkyl-C (O) OR ²⁸ , -SC ₁ -C ₆ -alkyl-C (O) OR ²⁸ , -C ₂ -C ₆ - alkenyl-C (= O) OR ²⁸ , -NR ²⁸ -C (= O) -C ₁ -C ₆ -alkyl-C (= O) OR ²⁸ , -NR ²⁸ -C (= O) -C ₁ -C _6- alkenyl-C (= O) OR ²⁸ , -C (= O) NH ²⁸ -C ₁ -C ₆ -alkyl-C (= O) OR ²⁸ , -C ₁ -C ₆ -alkyl-C (= O ) OR ²⁸ or —C (O) OR ²⁸ , C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl, or C ₂ -C ₆ alkynyl, which may optionally be substituted with one or more substituents selected from halogen, —CN, —CF ₃ , —OCF ₃ , —OR ^28, and —NR ²⁸ R ²⁹ , aryl, aryloxy, aryloxycarbonyl, aroyl, aryl-C ₁ -C ₆ alkoxy, aryl-C ₁ -C _6- alkyl, aryl-C ₂ -C ₆ alkenyl, aryl-C ₂ -C ₆ -alkynyl, heteroaryl, heteroaryl-C ₁ -C ₆ -alkyl, heteroaryl-C ₂ -C ₆ -alkenyl or heteroaryl-C ₁ -C ₆ alkynyl, the cyclic fragments of which may optionally be substituted with one or more substituents selected from halogen, -C (O) OR ²⁸ , -CN, -CF ₃ , -OCF ₃ , -NO ₂ , -OR ²⁸ , - NR ²⁸ R ²⁹ and C ₁ -C ₆ alkyl. 47. The zinc binding ligand according to claim 46, wherein R ²² , R ²³ and R ^{24 are} independently selected from hydrogen, halogen, —OCF ₃ , —OR ²⁸ , —NR ²⁸ R ²⁹ , —SR ²⁸ , —NR ²⁸ R ²⁹ , - NR ²⁸ C (O) OR ²⁹ , -OC (O) R ²⁸ , -OC ₁ -C ₆ -alkyl-C (O) OR ²⁸ , -SC ₁ -C ₆ -alkyl-C (O) OR ²⁸ , - C ₁ -C ₆ alkenyl-C (= O) OR ²⁸ , -C (= O) NR ²⁸ -C ₁ -C ₆ -alkyl-C (= O) OR ²⁸ , C ₁ -C ₆ -alkyl-C (= O) OR ²⁸ or —C (O) OR ²⁸ , C ₁ -C ₆ alkyl optionally substituted with one or more substituents selected from halogen, —CN, —CF ₃ , —OCF ₃ , —OR ^28, and - NR ²⁸ R ²⁹ , aryl, aryloxy, aroyl, aryl-C ₁ -C ₆ alkoxy, aryl-C ₁ -C ₆ -alkyl, heteroaryl, heteroaryl-C ₁ -C ₆ -alkyl, the cyclic fragments of which may optionally be substituted one or more substituents selected from halogen, —C (O) OR ²⁸ , —CN, —CF ₃ , —OCF ₃ , —NO ₂ , —OR ²⁸ , —NR ²⁸ R ^29, and C ₁ -C ₆ alkyl . 48. The zinc binding ligand of claim 47, wherein R ²² , R ^23, and R ^{24 are} independently selected from - hydrogen, halogen, -OCF ₃ , -OR ²⁸ , -NR ²⁸ R ²⁹ , -SR ²⁸ , -NR ²⁸ C (O) R ²⁹ , -NR ²⁸ C (O) OR ²⁹ , -OC (O) R ²⁸ , -OC ₁ -C ₆ -alkyl-C (O) OR ²⁸ , -SC ₁ -C ₆ -alkyl-C (O) OR ²⁸ , -C ₂ -C ₆ -alkenyl-C (= O) OR ²⁸ , -C (= O) NR ²⁸ -C ₁ -C ₆ -alkyl-C (= O) OR ²⁸ , -C ₁ -C ₆ -alkyl-C (= O) OR ²⁸ or -C (O) OR ²⁸ , C ₁ -C ₆ alkyl optionally substituted with one or more substituents selected from halogen, —CN or —CF ₃ , aryl, aryloxy, aroyl, aryl-C ₁ -C ₆ -alkoxy, aryl-C ₁ -C ₆ - alkyl, heteroaryl, heteroaryl-C ₁ -C ₆ -alkyl, the cyclic fragments of which may optionally be substituted with one or more substituents selected from halogen, —C (O) OH, —CN, —CF ₃ , —NO ₂ or C ₁ - ₆ alkyl. 49. The zinc binding ligand according to claim 39, wherein R ²⁰ is hydrogen or methyl. 50. The zinc binding ligand of claim 49, wherein R ²⁰ is hydrogen. 51. The zinc binding ligand according to claim 39, wherein R ²⁸ is hydrogen, C ₁ -C ₆ alkyl or aryl. 52. The zinc binding ligand according to claim 51, wherein R ²⁸ is hydrogen or C ₁ -C ₆ alkyl. 53. The zinc binding ligand according to claim 39, wherein R ²⁹ is hydrogen or C ₁ -C ₆ alkyl. 54. The zinc binding ligand of claim 39, wherein V is a valence bond. 55. The zinc binding ligand according to claim 39, wherein V is C ₁ -C ₆ alkylene optionally substituted with one or more hydroxy, C ₁ -C ₆ alkyl or aryl. 56. The zinc binding ligand according to claim 39, wherein L is C ₁ -C ₆ alkylene or arylene, where arylene is optionally substituted with substituents R ²⁵ , R ²⁶ and R ²⁷ , in an amount of up to three. 57. The zinc binding ligand according to claim 56, wherein L is C ₁ -C ₆ alkylene. 58. The zinc binding ligand according to claim 56, wherein L is phenylene, optionally substituted with substituents R ²⁵ , R ²⁶ and R ²⁷ , in an amount of up to three. 59. The zinc binding ligand according to claim 39, wherein R ²⁵ , R ²⁶ and R ^{27 are} independently selected from hydrogen, halogen, —CHF ₂ , —CF ₃ , —OCF ₃ , —OCHF ₂ , —OCH ₂ CF ₃ , —OCF ₂ CHF ₂ , -SCF ₃ , -NO ₂ , -OR ²⁸ , -NR ²⁸ R ²⁹ , -SR ²⁸ , -C (O) NR ²⁸ R ²⁹ , -OC (O) NR ²⁸ R ²⁹ , -NR ²⁸ C ( O) OR ²⁹ , -NR ²⁸ C (O) OR ²⁹ –CH ₂ C (O) NR ²⁸ R ²⁹ , -OCH ₂ C (O) NR ²⁸ R ²⁹ , -CH ₂ OR ²⁸ , -CH ₂ NR ²⁸ R ²⁹ , -OC (O) R ²⁸ , -OC ₁ -C ₆ -alkyl-C (O) OR ²⁸ , -SC ₁ -C ₆ -alkyl-C (O) OR ²⁸ , -C ₂ -C ₆ -alkenyl -C (= O) OR ²⁸ , -NR ²⁸ -C (= O) -C ₁ -C ₆ -alkyl-C (= O) OR ²⁸ , -NR ²⁸ -C (= O) -C ₁ -C ₆ -alkenyl-C (= O) OR ²⁸ , -C (= O) NR ²⁸ -C ₁ -C ₆ -alkyl-C (= O) OR ²⁸ , -C ₁ -C ₆ -alkyl-C (= O) OR ²⁸ or —C (O) OR ²⁸ , C ₁ -C ₆ alkyl, C ₁ -C ₆ alkenyl, or C ₂ -C ₆ alkynyl, which may optionally be substituted with one or more substituents selected from halogen, —CN, —CF ₃ , —OCF ₃ , —OR ^28, and —NR ²⁸ R ²⁹ , aryl, aryloxy, aryloxycarbonyl, aroyl, aryl-C ₁ -C ₆ alkoxy, aryl-C ₁ -C _6- alkyl, aryl-C ₂ -C ₆ alkenyl, aryl-C ₂ -C ₆ -alkynyl, heteroaryl, heteroaryl-C ₁ -C ₆ -alkyl, heteroaryl-C ₂ -C ₆ -alkenyl or heteroaryl-C ₂ -C ₆ alkynyl, the cyclic fragments of which may optionally be substituted with one or more substituents selected from halogen, -C (O) OR ²⁸ , -CN, -CF ₃ , -OCF ₃ , -NO ₂ , -OR ²⁸ , - NR ²⁸ R ²⁹ and C ₁ -C ₆ alkyl. 60. The zinc binding ligand of claim 59, wherein R ²⁵ , R ^26, and R ^{27 are} independently selected from hydrogen, halogen, —OCF ₃ , —OR ²⁸ , —NR ²⁸ R ²⁹ , —SR ²⁸ , —NR ²⁸ C (O) R ²⁹ , -NR ²⁸ C (O) OR ²⁹ , -OC (O) R ²⁸ , -OC ₁ -C ₆ -alkyl-C (O) OR ²⁸ , -SC ₁ -C ₆ -alkyl-C (O) OR ²⁸ , -C ₂ -C ₆ alkenyl-C (= O) OR ²⁸ , -C (= O) NR ²⁸ -C1-C ₆ -alkyl-C (= O) OR ²⁸ , -C ₁ -C ₆ -alkyl-C (= O) OR ²⁸ or -C (O) OR ²⁸ , C ₁ -C ₆ alkyl optionally substituted with one or more substituents selected from halogen, —CN, —CF ₃ , —OCF ₃ , - OR ²⁸ and –NR ²⁸ R ²⁹ , aryl, aryloxy, aroyl, aryl-C ₁ -C ₆ -alkoxy, aryl-C ₁ -C ₆ -alkyl, heteroaryl, heteroaryl-C ₁ -C ₆ -alkyl, the cyclic fragments of which may optionally be deputy scheny one or more substituents selected from halogen, -C (O) OR ^28, -CN, -CF _3, -OCF _3, -NO _2, -OR ^28, -NR ²⁸ R ²⁹ and C ₁ -C ₆ alkyl . 61. The zinc binding ligand according to claim 60, wherein R ²⁵ , R ²⁶ and R ^{27 are} independently selected from hydrogen, halogen, —OCF ₃ , —OR ²⁸ , —NR ²⁸ R ²⁹ , —SR ²⁸ , —NR ²⁸ C (O ) R ²⁹ , -NR ²⁸ C (O) OR ²⁹ , -OC (O) R ²⁸ , -OC ₁ -C ₆ -alkyl-C (O) OR ²⁸ , -SC ₁ -C ₆ -alkyl-C (O ) OR ²⁸ , -C ₂ -C ₆ alkenyl-C (= O) OR ²⁸ , -C (= O) NR ²⁸ -C ₁ -C ⁶ -alkyl-C (= O) OR ²⁸ , -C ₁ - C ₆ -alkyl-C (= O) OR ²⁸ or -C (O) OR ²⁸ , C ₁ -C ₆ -alkyl optionally substituted with one or more substituents selected from halogen, —CN or —CF ₃ , aryl, aryloxy , aroyl, aryl-C ₁ -C ₆ alkoxy, aryl-C ₁ -C ₆ -alkyl, heteroaryl, heteroaryl-C ₁ -C ₆ -alkyl, the cyclic fragments of which may optionally be substituted with one yl and more substituents selected from halogen, —C (O) OH, —CN, —CF ₃ , —NO ₂ , or C ₁ –C ₆ alkyl. 62. The zinc binding ligand of 39, wherein R ²¹ is hydrogen or methyl. 63. The zinc binding ligand according to claim 62, wherein R ²¹ is hydrogen. 64. The zinc binding ligand according to claim 39, wherein R ²⁸ is hydrogen, C ₁ -C ₆ alkyl or aryl. 65. The zinc binding ligand according to claim 64, wherein R ²⁸ is hydrogen or C ₁ -C ₆ alkyl. 66. The zinc binding ligand according to claim 39, wherein R ²⁹ is hydrogen or C ₁ -C ₆ alkyl. 67. The zinc binding ligand according to claim 39, wherein R ¹⁸ and R ^{19 are} independently selected from — hydrogen, halogen, —CN, —CF ₃ , —OCF ₃ , —NO ₂ , —OR ²⁸ , —NR ²⁸ R ²⁹ , —SR ²⁸ , -S (O) R ²⁸ , -S (O) ₂ R ²⁸ , -C (O) NR ²⁸ R ²⁹ , -CH ₂ OR ²⁸ , -OC (O) R ²⁸ , -OC ₁ -C ₆ - alkyl-C (O) OR ²⁸ , -SC ₁ -C ₆ -alkyl-C (O) OR ²⁸ or -C (O) OR ²⁸ , C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkenyl or C ₂ -C ₆ alkynyl, which may optionally be substituted with one or more substituents selected from halogen, —CN, —CF ₃ , —OCF ₃ , —OR ²⁸ and —NR ²⁸ R ²⁹ , aryl, aryloxy, aryl-C ₁ -C ₆ alkoxy, aryl-C ₁ -C ₆ -alkyl, heteroaryl, heteroaryl-C ₁ -C ₆ -alkyl, the cyclic fragments of which may optionally be substituted one or more substituents selected from halogen, —C (O) OR ²⁸ , —CN, —CF ₃ , —OCF ₃ , —NO ₂ , —OR ²⁸ , —NR ²⁸ R ^29, and C ₁ -C ₆ alkyl . 68. The zinc binding ligand according to claim 67, wherein R ¹⁸ and R ^{19 are} independently selected from hydrogen, halogen, —CN, —CF ₃ , —NO ₂ , —OR ²⁸ , —NR ²⁸ R ^29, or —C (O) OR ²⁸ , C ₁ -C ₆ alkyl optionally substituted with one or more substituents selected from halogen, —CN, —CF ₃ , —OCF ₃ , —OR ²⁸ and —NR ²⁸ R ²⁹ , aryl, aryloxy, aryl-C ₁ - C ₆ -alkyl, heteroaryl, cyclic fragments of which may optionally be substituted with one or more substituents selected from halogen, —C (O) OR ²⁸ , —CN, —CF ₃ , —OCF ₃ , —NO ₂ , —OR ²⁸ , -NR ²⁸ R ²⁹ and C ₁ -C ₆ alkyl. 69. The zinc binding ligand according to claim 39, wherein A is

70. The zinc-binding ligand according to any one of claims 1 to 3, where A represents the formula M-Q-T-, where M is

or

or

where W ¹ , W ² and W ³ independently represent OH, SH or NH ₂ and the phenyl, naphthalene or benzocarbazole rings are optionally independently substituted with one or more R ³⁴ ; Q is selected from the following: valence bond; - CH ₂ N (R ³⁰ ) - or -SO ₂ N (R ³¹ ) -; compounds of the formula

where Z ¹ represents S (O) ₂ or CH ₂ , Z ² represents N, —O— or —S— and n is 1 or 2; T represents C ₁ -C ₆ alkylene, C ₂ -C ₆ alkenylene or C ₂ -C ₆ alkynylene, which may optionally be substituted with one or more substituents selected from halogen, —CN, —CF ₃ , —OCF ₃ , -OR ³² or –NR ³² R ³³ , arylene, aryleneoxy, aryloxycarbonyl-, arooyl, aryl-C ₁ -C ₆ alkoxy, aryl-C ₁ -C ₆ -alkyl-, aryl -C ₂ -C ₆ -alkenyl-, -aryl-C ₁ -C ₆ -alkynyl-, heteroarylene, -heteroaryl-C ₁ -C ₆ -alkyl-, -heteroaryl-C ₁ -C ₆ -alkenyl- or -heteroaryl —C ₂ -C ₆ alkynyl— wherein the cyclic moieties are optionally substituted with one or more substituents selected from halogen, —C (O) OR ³² , —C (O) H , —CN, —CF ₃ , —OCF ₃ , —NO ₂ , —OR ³² , —NR ³² R ³³ , C ₁ -C ₆ alkyl or C ₁ -C ₆ alkanoyl, valence bond; R ³² and R ³³ independently represent hydrogen, C ₁ -C ₆ -alkyl, aryl-C ₁ -C ₆ -alkyl or aryl, or R ³² and R ³³ when attached to the same nitrogen atom, together with the specified a nitrogen atom can form a 3-8 membered heterocyclic ring, optionally containing one or two additional heteroatoms selected from nitrogen, oxygen and sulfur, and optionally containing one or two double bonds; R ³⁰ and R ³¹ independently represent hydrogen, C ₁ -C ₆ alkyl or C ₁ -C ₆ alkanoyl; R ³⁴ represents hydrogen, halogen, —CN, —CH ₂ CN, —CHF ₂ , —CF ₃ , —OCF ₃ , —OCHF ₂ , —OCH ₂ CF ₃ , —OCF ₂ CHF ₂ , —S (O) 2CF ₃ , -SCF ₃ , -NO ₂ , -OR ³² , -C (O) R ³² , -NR ³² R ³³ , -SR ³² , -NR ³² S (O) ₂ R ³³ , -S (O) ₂ NR ³² R ³³ , -S (O) NR ³² R ³³ , -S (O) R ³² , -S (O) ₂ R ³² , -C (O) NR ³² R ³³ , -OC (O) NR ³² R ³³ , -NR ³² C (O) R ³³ , -CH ₂ C (O) NR ³² R ³³ , -OCH ₂ C (O) NR ³² R ³³ , -CH ₂ OR ³² , -CH ₂ NR ³² R ³³ , - OC (O) R ³² , -OC ₁ -C ₆ -alkyl-C (O) OR ³² , -SC ₁ -C ₆ -alkyl-C (O) OR ³² , -C ₂ -C ₆ -alkenyl-C ( = O) OR ³² , -NR ³² -C (= O) -C ₁ -C ₆ -alkyl-C (= O) OR ³² , -NR ³² -C (= O) -, C ₁ -C ₆ alkenyl -C (= O) OR ³² , C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkanoyl or -C (O) OR ³² . 71. The zinc binding ligand of claim 70, wherein M is

or

72. The zinc binding ligand of claim 71, wherein M is

73. The zinc binding ligand of claim 71, wherein M is

74. The zinc binding ligand of claim 71, wherein M is

75. The zinc binding ligand of claim 71, wherein M is

76. The zinc binding ligand according to claim 70, wherein Q is a valence bond, —CH ₂ N (R ³⁰ ) - or —SO ₂ N (R ³¹ ) -. 77. The zinc binding ligand of claim 76, wherein Q is a valence bond. 78. The zinc binding ligand of claim 70, wherein T is a valence bond, C ₁ -C ₆ alkylene, C ₂ -C ₆ alkenylene, or C ₂ -C ₆ alkynylene, which may optionally be substituted with one or more substituents, selected from halogen, —CN, —CF ₃ , —OCF ₃ , —OR ^32, and —NR ³² R ³³ , arylene or heteroarylene, the cyclic moieties of which are optionally substituted as defined in claim 70. 79. The zinc binding ligand according to claim 78, wherein T is a valence bond, arylene or heteroarylene, the cyclic moieties of which are optionally substituted, as defined in clause 70. 80. The zinc binding ligand according to claim 70, wherein T is phenylene or naphthalene. 81. The zinc binding ligand according to claim 70, wherein the cyclic moiety in T is optionally substituted with halogen, —C (O) OR ³² , —CN, —CF ₃ , —OR ³² , —NR ³² R ³³ , C ₁ -C ₆ alkyl or C ₁ -C ₆ alkanoyl. 82. The zinc binding ligand of claim 81, wherein the cyclic moiety in T is optionally substituted with halogen, —C (O) OR ³² , —OR ³² , —NR ³² R ³³ , C ₁ -C ₆ alkyl, or C ₁ -C ₆ - alkanoyl. 83. The zinc binding ligand of claim 81, wherein the cyclic moiety in T is optionally substituted with halogen, —C (O) OR ³² or —OR ³² . 84. The zinc binding ligand of claim 70, wherein T is a valence bond. 85. The zinc binding ligand of claim 70, wherein R ³⁰ and R ³¹ are independently hydrogen or C ₁ -C ₆ alkyl. 86. The zinc binding ligand of claim 70, wherein R ³⁴ is hydrogen, halogen, —CN, —CF ₃ , —OCF ₃ , —SCF ₃ , —NO ₂ , —OR ³² , —C (O) R ³² , - NR ³² R ³³ , -SR ³² , -C (O) NR ³² R ³³ , -ОС (О) NR ³² R ³³ , -NR ³² C (О) R ³³ , -OC (O) R ³² , -ОС ₁ -C ₆ -alkyl-C (O) OR ³² , -SC ₁ -C ₆ -alkyl-C (O) OR ³² or C (O) OR ³² . 87. The zinc binding ligand of claim 86, wherein R ³⁴ is hydrogen, halogen, —CF ₃ , —NO ₂ , —OR ³² , —NR ³² R ³³ , —SR ³² , —NR ³² C (O) R ^33, or -C (O) OR ³² . 88. The zinc binding ligand of claim 87, wherein R ³⁴ is hydrogen, halogen, —CF ₃ , —NO ₂ , —OR ³² , —NR ³² R ^33, or —NR ³² C (O) R ³³ . 89. The zinc binding ligand of claim 88, wherein R ³⁴ is hydrogen, halogen, or —OR ³² . 90. The zinc binding ligand according to claim 70, wherein R ³² and R ^{33 are} independently hydrogen, C ₁ -C ₆ alkyl or aryl. 91. The zinc binding ligand according to claim 90, wherein R ³² and R ³³ independently represent hydrogen or C ₁ -C ₆ alkyl. 92. The zinc-binding ligand according to any one of claims 1 to 3, where A represents

where A ¹ represents a valence bond, C ₁ -C ₆ alkylene, -NH-C (= 0) -A ² , -C ₁ -C ₆ -alkyl-S-, -C ₁ -C ₆ -alkyl-O -, -C (= O) -or -C (= O) NH-, where any C ₁ -C ₆ -alkyl moiety is optionally substituted with R ^1A ; And ² represents a valence bond, C ₁ -C ₆ -alkylene, C ₁ -C ₆ -alkenylene or -C ₁ -C ₆ -alkyl-O-; R ^1A is C ₁ -C ₆ alkyl, aryl, wherein the alkyl or aryl moieties are optionally substituted with one or more halogen, cyano, nitro, amino; AR ¹ is a valence bond, arylene or heteroarylene, wherein the aryl or heteroaryl moieties are optionally independently substituted with one or more R ^1B ; R ^{1B is} selected from hydrogen, halogen, —CN, —CH ₂ CN, —CHF ₂ , —CF ₃ , —OCF ₃ , —OCHF ₂ , —OCH ₂ CF ₃ , —OCF ₂ CHF ₂ , —S (O) ₂ CF ₃ , -OS (O) ₂ CF ₃ , -SCF ₃ , -NO ₂ , -OR ^1C , -NR ^1C R ^1D , -SR ^1C , -NR ^1C S (O) ₂ R ^1D , -S (O) ₂ NR ^1C R ^1D , -S (O) NR ^1C R ^1D , -S (O) R ^1C , -S (O) ₂ R ^1C , -OS (O) ₂ R ^1C , -C (O) NR ^1C R ^1D , -OC (O) NR ^1C R ^1D , -NR ^1C C (O) R ^1D , -CH ₂ C (O) NR ^1C R ^1D , -OC ₁ -C ₆ -alkyl-C (O) NR ^1C R ^1D , -CH ₂ OR ^1C , -CH ₂ OC (O) R ^1C , -CH ₂ NR ^1C R ^1D , -OC (O) R ^1C , -OC ₁ -C ₆ -alkyl-C (O) OR ^lC , -OC ₁ -C ₆ -alkyl-OR ^1C , -SC ₁ -C ₆ -alkyl-C (O) OR ^1C , -C ₂ -C ₆ -alkenyl-C (= O) OR ^1C , -NR ^1C -C (= O) -C ₁ -C ₆ -alkyl-C (= O) OR ^1C , -NR ^1C -C (= O) -C ₁ -C ₆ -alkenyl-C (= O) OR ^1C , -C ( O) OR ^1C , -C ₂ -C ₆ alkenyl-C (= O) OR ^1C , = O, -NH-C (= O) -OC ₁ -C ₆ -alkyl or -NH-C (= O) -C (= O) -OC ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl or C ₂ -C ₆ -alkynyl a, which may optionally be substituted with one or more substituents selected from halogen, —CN, —CF ₃ , —OCF ₃ , —OR ¹⁰ and –NR ^1C R ^1D , aryl, aryloxy, aryloxycarbonyl, aroyl, arylsulfanyl, aryl-C ₁ -C ₆ alkoxy, aryl-C ₁ -C ₆ -alkyl, aryl-C ₂ -C ₆ -alkenyl, aroyl-C ₂ -C ₆ -alkenyl, aryl-C ₂ -C ₆ -alkynyl, heteroaryl, heteroaryl -C ₁ -C ₆ -alkyl, heteroaryl-C ₂ -C ₆ -alkenyl or heteroaryl-C ₁ -C ₆ -alkynyl, cyclic fragments of which may optionally be substituted with one or more substituents selected from halogen, -C (O) OR ^1C , -CH ₂ C (O) OR ^1C , -CH ₂ OR ^1C , -CN, -CF ₃ , -OCF ₃ , -NO ₂ , -OR ^1C , -NR ^1C R ^1D and C ₁ -C ₆ alkyl; R ^1C and R ^{1D are} independently hydrogen, —OH, C ₁ -C ₆ alkyl, C ₁ -C ₆ alkenyl, aryl-C ₁ -C ₆ alkyl or aryl, where the alkyl moieties may optionally be substituted with one or more substituents selected from halogen, —CN, —CF ₃ , —OCF ₃ , —OC ₁ —C ₆ alkyl, —C (O) —OC ₁ —C ₆ alkyl, —COOH and —NH ₂ , and aryl the fragments may optionally be substituted with halogen, —C (O) OC ₁ —C ₆ alkyl, —COOH, —CN, —CF ₃ , —OCF ₃ , —NO ₂ , —OH, —OC ₁ —C ₆ alkyl, -NH ₂ , C (= O) or C ₁ -C ₆ alkyl; R ^1C and R ^1D , when attached to the same nitrogen atom, together with the specified nitrogen atom can form a 3-8-membered heterocyclic ring, optionally containing one or two additional heteroatoms selected from nitrogen, oxygen and sulfur, and optionally containing one or two double bonds; C ¹ represents a valence bond, C ₁ -C ₆ alkylene, -C ₁ -C ₆ -alkyl-O-, -C ₁ -C ₆ -alkyl-NH-, -NH-C ₁ -C ₆ -alkyl, -NH-C (= O) -, -C (= O) -NH, -OC ₁ -C ₆ -alkyl, -C (= O) - or -C ₁ -C ₆ -alkyl-C (= O) —N (R ^1E ) -, wherein the alkyl moieties are optionally substituted with one or more R ^1F independently; R ^1E and R ^{1F are} independently selected from C ₁ -C ₆ alkyl, aryl optionally substituted with one or more halogen, —COOH; AR ² is a valence bond, C ₁ -C ₆ alkylene, C ₂ -C ₆ alkenylene, C ₂ -C ₆ alkynylene, where the alkyl, alkenyl and alkynyl moieties are optionally substituted with one or more R ^2A independently, arylene, - aryloxy-, aryloxycarbonyl-, aryl-C ₁ -C ₆ -alkyl, -arylo-, -aryl-C ₁ -C ₆ -alkoxy-, -aryl-C ₂ -C ₆ -alkenyl-, aryl-C ₁ -C ₆ -alkynyl-, heteroarylene, -heteroaryl-C ₁ -C ₆ -alkyl-, -heteroaryl-C ₂ -C ₆ -alkenyl-, -heteroaryl-C ₂ -C ₆ -alkynyl-, where aryl and heteroaryl fragments optionally substituted with one or more R ^2A independently; R ^2A represents C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, aryl, aryloxy, aryl-C ₁ -C ₆ alkoxy, -C (= O) -NH-C ₁ -C ₆ alkylaryl , heteroaryl, heteroaryl-C ₁ -C ₆ alkoxy, -C ₁ -C ₆ -alkyl-COOH, -OC ₁ -C ₆ -alkyl-COOH, -S (O) ₂ R ^2B , -C ₂ -C ₆ -alkenyl-COOH, -OR ^2B , -NO ₂ , halogen, -COOH, -CF ₃ , -CN, -N (R ^2B R ^2C ), where the aryl and heteroaryl moieties are optionally substituted with one or more C ₁ -C ₆ - alkyl, C ₁ -C ₆ alkoxy, -C ₁ -C ₆ -alkyl-COOH, -C ₂ -C ₆ -alkenyl-COOH, -OR ^2B , -NO ₂ , halogen, -COOH, -CF ₃ , - CN or -N (R ^2B R ^2C ); R ^2B and R ^{2C are} independently selected from hydrogen and C ₁ -C ₆ alkyl. 93. The zinc binding ligand according to claim 92, wherein A ¹ is a valence bond, C ₁ -C ₆ alkylene, -NH-C (= O) -A ² -, -C ₁ -C ₆ -alkyl-S-, -C ₁ -C ₆ -alkyl-O- or -C (= O) -, where any fragment of C ₁ -C ₆ -alkyl is optionally substituted with R ^1A . 94. The zinc binding ligand according to claim 93, wherein A ¹ is a valence bond, C ₁ -C ₆ alkylene, -NH-C (= O) -A ² -, -C ₁ -C ₆ -alkyl-S- or -C ₁ -C ₆ -alkyl-O-, where any fragment of C ₁ -C ₆ -alkyl is optionally substituted with R ^1A . 95. The zinc binding ligand according to claim 94, wherein A ¹ is a valence bond, C ₁ -C ₆ alkylene or -NH-C (= O) -A ² , where any fragment of C ₁ -C ₆ alkyl is optionally substituted with R ^1A . 96. The zinc binding ligand according to claim 95, wherein A ¹ is a valence bond or C ₁ -C ₆ alkylene, where any fragment of C ₁ -C ₆ alkyl is optionally substituted with R ^1A . 97. The zinc binding ligand of claim 96, wherein A ¹ is a valence bond. 98. The zinc binding ligand of claim 92, wherein A ² is a valence bond or —C ₁ -C ₆ -alkyl-O—. 99. The zinc binding ligand of claim 98, wherein A ² is a valence bond. 100. The zinc binding ligand of claim 92, wherein AR ¹ is arylene or heteroarylene, wherein the fragments of arylene or heteroarylene are optionally substituted with one or more R ¹⁸ independently. 101. The zinc binding ligand according to claim 100, wherein AR ^{1 is} selected from the group of compounds consisting of phenylene, biphenylylene, naphthylene, anthracene, phenanthrene, fluorenylene, indenylene, azulelen, furylene, thienylene, pyrrolylene, oxazolylene, thiazolylene, isazazole, imidaz , 1,2,3-triazolylene, 1,2,4-triazolylene, pyranylene, pyridylene, pyridazinylene, pyrimidinyl, pyrazinylene, 1,2,3-triazinylene, 1,2,4-triazinylene, 1,3,5-triazinyl , 1,2,3-oxadiazolylene, 1,2,4-oxadiazolylene, 1,2,5-oxadiazolylene, 1,3,4-oxadiazolylene, 1,2,3-t adiazolylene, 1,2,4-thiadiazolylene, 1,2,5-thiadiazolylene, 1,3,4-thiadiazolylene, tetrazolylene, thiadiazinylene, indolylene, isoindolylene, benzofurylene, benzothienylene, indazolylene, benzimidazolylene, benzothiazoleazoleazoleazoleazole, benzene purinylene, quinazolinylene, quinolisinylene, quinolinylylene, isoquinolinylene, quinoxalininyl, naphthyridinylylene, pteridinylylene, carbazolylene, azepinylene, diazepinylene or acridinylene, optionally substituted with one or more R ^1B independently. 102. The zinc binding ligand of claim 101, wherein AR ^{1 is} selected from phenylene, biphenylylene, naphthylene, pyridinyl, furylene, indolylene or carbazolylene, optionally substituted with one or more R ^1B independently. 103. The zinc binding ligand of claim 102, wherein AR ^{1 is} selected from the group of compounds consisting of phenylene, indolylene or carbazolylene, optionally substituted with one or more R ^1B independently. 104. The zinc binding ligand of claim 103, wherein AR ¹ is phenylene optionally substituted with one or more R ^1B independently. 105. The zinc binding ligand of claim 103, wherein AR ¹ is indolylene optionally substituted with one or more R ^1B independently. 106. The zinc binding ligand of claim 105, wherein AR ¹ is

107. The zinc binding ligand of claim 103, wherein AR ¹ is carbazolylene optionally substituted with one or more R ^1B independently. 108. The zinc binding ligand of claim 107, wherein AR ¹ is

109. The zinc binding ligand according to claim 92, wherein R ^{1B is} selected from hydrogen, halogen, —CN, —CF ₃ , —OCF ₃ , —NO ₂ , —OR ^1C , —NR ^1C R ^1D , —SR ^1C , —S ( O) ₂ R ^1C , -NR ^1C C (O) R ^1D , -OC ₁ -C ₆ -alkyl-C (O) NR ^1C R ^1D , -C ₂ -C ₆ -alkenyl-C (= O) OR ^lC , -C (O) OR ^1C , = O, -NH-C (= O) -OC ₁ -C ₆ -alkyl or -NH-C (= O) -С (= O) -OC ₁ -C ₆ - alkyl, C ₁ -C ₆ alkyl or C ₁ -C ₆ alkenyl, which may optionally be substituted with one or more substituents selected from halogen, —CN, —CF ₃ , —OCF ₃ , —OR ^1C, and —NR ^1C R ^1D , aryl, aryloxy, aryl-C ₁ -C ₆ -alkoxy, aryl-C ₁ -C ₆ -alkyl, aryl-C ₂ -C ₆ -alkenyl, heteroaryl, heteroaryl-C ₁ -C ₆ -alkyl or heteroaryl -C ₂ -C ₆ alkenyl cyclic moiety which may optionally be substituted with one or more substituents selected from halogen, —C (O) OR ^1C , —CN, —CF ₃ , —OCF ₃ , —NO ₂ , —OR ^1C , —NR ^1C R ^1D and C ₁ -C ₆ -alkyl. 110. The zinc binding ligand of claim 109, wherein R ^{13 is} selected from hydrogen, halogen, —CF ₃ , —NO ₂ , —OR ^1C , —NR ^1C R ^1D , —C (O) OR ^1C , = O, —NH— C (= O) -OC ₁ -C ₆ -alkyl or -NH-C (= O) -C (= O) -OC ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkyl. 111. The zinc binding ligand of claim 92, wherein R ^1C and R ^{1D are} independently hydrogen, C ₁ -C ₆ alkyl or aryl, where the aryl moieties may optionally be substituted with halogen or —COOH. 112. The zinc binding ligand of claim 111, wherein R ^1C and R ^{1D are} independently hydrogen, methyl, ethyl, or phenyl, wherein the phenyl moieties may optionally be substituted with halogen or —COOH. 113. The zinc binding ligand of claim 92, wherein C ¹ is a valence bond, —C ₁ -C ₆ alkylene, —C ₁ -C ₆ -alkyl-O—, -C ₁ -C ₆ -alkyl-NH—, -NH-C ₁ -C ₆ -alkyl, -NH-C (= O) -, -C (= O) -NH-, -OC ₁ -C ₆ -alkyl, -C (= O) - or -C ₁ -C ₆ -alkyl-C (= O) -N (R ^1E ) -, where the alkyl moieties are optionally substituted with one or more R ^1F independently. 114. The zinc binding ligand according to claim 113, wherein C ¹ is a valence bond, —CH ₂ -, —CH ₂ —CH ₂ -, —CH ₂ —O—, —CH ₂ —CH ₂ —O—, —CH ₂ -NH-, -CH ₂ -CH ₂ -NH-, -NH-CH ₂ -, -NH-CH ₂ -CH ₂ -, -NH-C (= O) -, -C (= O) -NH- , —O — CH ₂ , —O — CH ₂ —CH ₂ -, or —C (= O) -. 115. The zinc binding ligand of claim 92, wherein R ^1E and R ^{1F are} independently selected from C ₁ -C ₆ alkyl. 116. The zinc binding ligand of claim 92, wherein AR ² is a valence bond, C ₁ -C ₆ alkylene, wherein the alkyl is optionally substituted with one or more R ^2A independently, arylene, aryl-C ₁ -C ₆ alkyl, heteroarylene, where fragments of arylene and heteroarylene are optionally substituted with one or more R ^2A independently. 117. The zinc binding ligand of claim 116, wherein AR ² is a valence bond, C ₁ -C ₆ alkylene, where alkylene is optionally substituted with one or more R ^2A independently, phenyl, phenyl-C ₁ -C ₆ alkyl, where the fragments phenylene is optionally substituted with one or more R ^2A independently. 118. The zinc binding ligand of claim 92, wherein R ^2A is C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, aryl, aryloxy, heteroaryl, -C ₁ -C ₆ alkyl-COOH, -OC ₁ -C ₆ -alkyl-COOH, -S (O) ₂ R ^2B , -C ₂ -C ₆ -alkenyl-COOH, -OR ^2B , -NO ₂ , halogen, -COOH, -CF ₃ , -CN, -N (R ^2B R ^2C ), wherein the aryl or heteroaryl moieties are optionally substituted with one or more C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, -C ₁ -C ₆ -alkyl-COOH, -C ₂ -C ₆ -alkenyl-COOH, -OR ^2B , -NO ₂ , halogen, -COOH, -CF ₃ , -CN or –N (R ^2B R ^2C ). 119. The zinc-binding ligand of claim 118, wherein R ^2A is C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, aryl, -OR ^2B , -NO ₂ , halogen, -COOH, -CF ₃ , - CN, —N (R ^2B R ^2C ), wherein the aryl is optionally substituted with one or more C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, -OR ^2B , -NO ₂ , halogen, —COOH, —CF ₃ , —CN or –N (R ^2B R ^2C ). 120. The zinc binding ligand according to claim 19, wherein R ^2A is C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, aryl, halogen, -CF ₃ , where aryl is optionally substituted with one or more C ₁ -C ₆ -alkyl, halogen, -COOH, -CF ₃ or -CN. 121. The zinc binding ligand of claim 120, wherein R ^2A is C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, phenyl, halogen, —CF ₃ , where phenyl is optionally substituted with one or more C ₁ -C ₆ -alkyl, halogen, -COOH, -CF ₃ or -CN. 122. The zinc-binding ligand according to any one of claims 1 to 3, where A represents

where AR ³ is C ₁ -C ₆ alkylene, arylene, heteroarylene, -aryl-C _1-6 -alkyl- or -aryl-C _2-6 -alkenyl-, where alkylene or alkenylene is optionally substituted with one or more substituents, independently selected from halogen, —CN, —CF ₃ , —OCF ₃ , aryl, —COOH and —NH ₂ , and arylene or heteroarylene are optionally substituted with one or more R ^3A independently; R ^{3A is} independently selected from hydrogen, halogen, —CN, —CH ₂ CN, —CHF ₂ , —CF ₃ , —OCF ₃ , —OCHF ₂ , —OCH ₂ CF ₃ , —OCF ₂ CHF ₂ , —S (O) ₂ CF ₃ , -OS (O) ₂ CF ₃ , -SCF ₃ , -NO ₂ , -OR ^3B , -NR ^3B R ^3C , -SR ^3B , -NR ^3B S (O) ₂ R ^3C , -S (O ) ₂ NR ^3B R ^4C , -S (O) NR ^3B R ^3C , -S (O) R ^3B , -S (O) ₂ R ^3B , -OS (O) 2R ^3B , -C (O) NR ^3B R ^3C , -OC (O) NR ^3B R ^3C , -NR ^3B C (O) R ^3C , -CH ₂ C (O) NR ^3B R ^3C , -OC ₁ -C ₆ -alkyl-C (O) NR ^3B R ^3C , -CH ₂ OR ^3B , -CH ₂ OC (O) R ^3B , -CH ₂ NR ^3B R ^3C , -OC (O) R ^3B , -OC ₁ -C ₆ -alkyl-C (O) OR ^3B , -OC ₁ -C ₆ -alkyl-OR ^3B , -SC ₁ -C ₆ -alkyl-C (O) OR ^3B , -C ₂ -C ₆ -alkenyl-C (= O) OR ^3B , -NR ^3B -C (= O) -C ₁ -C ₆ -alkyl-C (= O) OR ^3B , -NB ^3B -C (= O) -C ₁ -C ₆ -alkenyl-C (= O) OR ^3B , -C ( O) OR ^3B or —C ₂ -C ₆ alkenyl-C (= O) R ^3B , C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl or C ₂ -C ₆ alkynyl, which may be optional o are substituted by one or more substituents selected from halogen, —CN, —CF ₃ , —OCF ₃ , —OR ^3B, and —NR ^3B R ^3C , aryl, aryloxy, aryloxycarbonyl, aroyl, arylsulfanyl, aryl-C ₁ -C ₆ - alkoxy, aryl-C ₁ -C ₆ -alkyl, aryl-C ₂ -C ₆ -alkenyl, aroyl-C ₂ -C ₆ -alkenyl, aryl-C ₂ -C ₆ -alkynyl, heteroaryl, heteroaryl-C ₁ -C _6- alkyl, heteroaryl-C ₂ -C ₆ alkenyl or heteroaryl-C ₂ -C ₆ -alkynyl, the cyclic fragments of which may optionally be substituted with one or more substituents selected from halogen, —C (O) OR ^3B , —CH ₂ C (O) OR ^3B , —CH ₂ OR ^3B , —CN, —CF ₃ , —OCF ₃ , —NO ₂ , —OR ^3B , —NR ^3B R ^3C, and C ₁ -C ₆ alkyl; R ^3B and R ^3C independently represent hydrogen, OH, CF ₃ , C ₁ -C ₁₂ -alkyl, aryl-C ₁ -C ₆ -alkyl, -C (= O) -C ₁ -C ₆ -alkyl or aryl, wherein the alkyl groups may optionally be substituted with one or more substituents selected from halogen, —CN, —CF ₃ , —OCF ₃ , —OC ₁ —C ₆ alkyl, —C (O) —OC ₁ —C ₆ alkyl, —C (═O) R ^3D , —COOH and —NH ₂ , and the aryl groups may optionally be substituted with halogen, —C (O) OC ₁ —C ₆ alkyl, —COOH, —CN, —CF ₃ , —OCF ₃ , -NO ₂ , -OH, -OC ₁ -C ₆ -alkyl, -NH ₂ , C (= O) or C ₁ -C ₆ -alkyl; R ^3B and R ^3C , when attached to the same nitrogen atom, together with the specified nitrogen atom can form a 3-8-membered heterocyclic ring, optionally containing one or two additional heteroatoms selected from nitrogen, oxygen and sulfur, and optionally containing one or two double bonds; R ^3D is C ₁ -C ₆ alkyl, aryl optionally substituted with one or more halogens or heteroaryl optionally substituted with one or more C ₁ -C ₆ alkyl. 123. The ligand of Tsinksvyazyvayuschy p.122 wherein AR ³ is arylene, heteroarylene or aryl-C ₁ - ₆ alkyl, wherein alkyl is optionally substituted with one or more substituents independently selected from halogen, -CN, -CF _3, —OCF ₃ , aryl, —COOH and –NH ₂ , and arylene or heteroarylene are optionally substituted with one or more R ^3A independently. 124. The zinc binding ligand of claim 123, wherein AR ³ is arylene optionally substituted with one or more R ^3A independently. 125. The zinc binding ligand of claim 124, wherein AR ³ is phenylene, naphthalene, or anthranylene, optionally substituted with one or more R ^3A independently. 126. The zinc binding ligand of claim 125, wherein AR ³ is phenylene optionally substituted with one or more R ^3A independently. 127. The zinc binding ligand of claim 122, wherein R ^{3A is} independently selected from halogen, —CN, —CF ₃ , —NO ₂ , —OR ^3B , —NR ^3B R ^3C , —SR ^3B , —OC ₁ —C ₆ -alkyl —C (O) OR ^3B or —C (O) OR ^3B , C ₁ -C ₆ alkyl optionally substituted with one or more substituents selected from halogen, —CN, —CF ₃ , —OCF ₃ , —OR ^3B, and -NR ^3B R ^3C , aryl, aryl-C ₁ -C ₆ -alkyl, heteroaryl or heteroaryl-C ₁ -C ₆ -alkyl, the cyclic fragments of which may optionally be substituted with one or more substituents selected from halogen, -C (O (O ) OR ^3B , —CN, —CF ₃ , —OCF ₃ , —NO ₂ , —OR ^3B , —NR ^3B R ^3C, and C ₁ -C ₆ alkyl. 128. The zinc binding ligand of claim 127, wherein R ^{3A is} independently selected from halogen, —OR ^3B , —NR ^3B R ^3C , —C (O) OR ^3B , —OC ₁ —C ₆ -alkyl-C (O) OR ^3B or C ₁ -C ₆ alkyl. 129. The zinc-binding ligand of claim 122, wherein R ^3B and R ^{3C are} independently hydrogen, CF ₃ , C ₁ -C ₁₂ alkyl or —C (═O) —C ₁ -C ₆ alkyl; R ^3B and R ^3C , when attached to the same nitrogen atom, can form a 3-8 membered heterocyclic ring together with the specified nitrogen atom. 130. The zinc-binding ligand according to any one of claims 1 to 3, where A represents

wherein AR ⁴ is C ₁ -C ₆ alkylene, arylene, heteroarylene, aryl-C _1-6 alkyl, or aryl C _2-6 alkenyl, wherein alkylene or alkenylene is optionally substituted with one or more substituents, independently selected from halogen, —CN, —CF ₃ , —OCF ₃ -, aryl, —COOH and –NH ₂ , and arylene or heteroarylene are optionally substituted with one or more R ^4A independently; R ^{4A is} independently selected from hydrogen, halogen, —CN, —CH ₂ CN, —CHF ₂ , —CF ₃ , —OCF ₃ , —OCHF ₂ , OCH ₂ CF ₃ , —OCF ₂ CHF ₂ , —S (O) ₂ CF ₃ , -OS (O) ₂ CF ₃ , -SCF ₃ , -NO ₂ , -OR ^4B , -NR ^4B R ^4C , -SR ^4B , -NR ^4B S (O) ₂ R ^4C , -S (O) ₂ NR ^4B R ^4C , -S (O) NR ^4B R ^4C , -S (O) R ^4B , -S (O) ₂ R ^4B , -OS (O) ₂ R ^4B , -C (O) NR ^4B R ^4C , -OC (O) NR ^4B R ^4C , -NR ^4B C (O) R ^4C , -CH ₂ C (O) NR ^4B R ^4C , -OC ₁ -C ₆ -alkyl-C (O) NR ^4B R ^4C , -CH ₂ OR ^4B , -CH ₂ OC (O) R ^4B , -CH ₂ NB ^4B R ^4C , -OC (O) R ^4B , -OC ₁ -C ₆ -alkyl-C (O) OR ^4c , -OC ₁ -C ₆ -alkyl-OR ^4B , -SC ₁ -C ₆ -alkyl-C (O) OR ^4B , -C ₂ -C ₆ -alkenyl-C (= O) OR ^4B , -NR ^4B -C (= O) -C ₁ -C ₆ -alkyl-C (= O) OR ^4c , -NR ^4B -C (= O) -C ₁ -C ₆ -alkenyl-C (= O) OR ^4B , -C ( O) oR ^4B, or -C ₂ -C ₆ -alkenyl-C (= O) oR ^4B, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl or C ₂ -C ₆ -alkynyl, which may be optional of substituted with one or more substituents selected from halogen, -CN, -CF _3, -OCF _3, -OR ^4B, and -NR ^4B R ^4C, aryl, aryloxy, aryloxycarbonyl, aroyl, arylsulfanyl, aryl-C ₁ -C ₆ - alkoxy, aryl-C ₁ -C ₆ -alkyl, aryl-C ₂ -C ₆ -alkenyl, aroyl-C ₂ -C ₆ -alkenyl, aryl-C ₂ -C ₆ -alkynyl, heteroaryl, heteroaryl-C ₁ -C _6- alkyl, heteroaryl-C ₂ -C ₆ -alkenyl or heteroaryl-C ₂ -C ₆ -alkynyl, the cyclic fragments of which may optionally be substituted with one or more substituents selected from halogen, —C (O) OR ^4B , —CH ₂ C (O) OR ^4B , —CH ₂ OR ^4B , —CN, —CF ₃ , —OCF ₃ , —NO ₂ , —OR ^4B , —NR ^4B R ^4C, and C ₁ -C ₆ alkyl; R ^4B and R ^4C independently represent hydrogen, OH, CF ₃ , C ₁ -C ₁₂ -alkyl, aryl-C ₁ -C ₆ -alkyl, -C (= O) -R ^4D or aryl, where alkyl groups may optionally be substituted by one or more substituents selected from halogen, —CN, —CF ₃ , —OCF ₃ , —OC ₁ —C ₆ alkyl, —C (O) OC ₁ —C ₆ alkyl, —COOH, and —NH ₂ , and the aryl groups may optionally be substituted with halogen, —C (O) OC ₁ —C ₆ alkyl, —COOH, —CN, —CF ₃ , —OCF ₃ , —NO ₂ , —OH, —OC ₁ —C ₆ -alkyl, -NH ₂ , C (= O) or C ₁ -C ₆ -alkyl; R ^4B and R ^4C , when attached to the same nitrogen atom, can form a 3-8 membered heterocyclic ring with the indicated nitrogen atom, optionally containing one or two additional heteroatoms selected from nitrogen, oxygen and sulfur, and optionally containing one or two double bonds; R ^4D is C ₁ -C ₆ alkyl, aryl optionally substituted with one or more halogens or heteroaryl optionally substituted with one or more C ₁ -C ₆ alkyl. 131. The zinc binding ligand of claim 130, wherein AR ⁴ is arylene, heteroarylene or aryl-C ₁ -C ₆ -alkyl-, where the alkyl is optionally substituted with one or more substituents independently selected from halogen, —CN, —CF ₃ , —OCF ₃ , aryl, —COOH and —NH ₂ , and arylene or heteroaryl are optionally substituted with one or more R ^4A independently. 132. The zinc binding ligand of claim 131, wherein AR ⁴ is arylene or heteroarylene optionally substituted with one or more R ^4A independently. 133. The zinc binding ligand according to Claim 131, wherein AR ⁴ is phenylene, naphthylene, antrylene, thienylene, pyridylene or benzodioxylene, optionally substituted with one or more R ^4A independently. 134. The zinc binding ligand of claim 133, wherein AR ⁴ is phenylene optionally substituted with one or more R ^4A independently. 135. The zinc binding ligand of claim 130, wherein R ^{4A is} independently selected from hydrogen, halogen, —CF ₃ , —OR ^4B , —NR ^4B R ^4C , C ₁ -C ₆ alkyl, aryl-C ₂ -C ₆ alkenyl or aryl, optionally substituted with one or more substituents selected from halogen, —CF ₃ or —OR ^4B . 136. The zinc binding ligand of claim 130, wherein R ^4B and R ^{4C are} independently hydrogen, CF ₃ , C ₁ -C ₁₂ alkyl, —C (═O) —R ^4D, or aryl. 137. The zinc binding ligand of claim 130, wherein R ^4D is C ₁ -C ₆ alkyl, phenyl optionally substituted with one or more halogens, or heteroaryl selected from isoxazole and thiadiazole optionally substituted with one or more C ₁ -C ₆ -alkyls. 138. The zinc binding ligand according to claim 1, where G ^B has the formula –B ¹ -B ² -C (O) -, -B ¹ -B ² -SO ₂ - or –B ¹ -B ² -CH ₂ -, where B ¹ and B ² are as defined in claim 1. 139. The zinc-binding ligand according to claim 1, where G ^B has the formula –B ¹ -B ² -C (O) -, -B ¹ -B ² -SO ₂ - or –B ¹ -B ² -NH-, where B ¹ and B ² are as defined in claim 1. 140. The zinc-binding ligand according to claim 1, where G ^B has the formula –B ¹ -B ² -C (O) -, -B ¹ -B ² -CH ₂ - or –B ¹ -B ² -NH-, where B ¹ and B ² are as defined in claim 1. 141. The zinc-binding ligand according to claim 1, where G ^B has the formula –B ¹ -B ² -CH ₂ -, -B ¹ -B ² -SO ₂ - or –B ¹ -B ² -NH-, where B ¹ and In ² such as defined in claim 1. 142. The zinc-binding ligand according to claim 1, where G ^B has the formula –B ¹ -B ² -C (O) - or –B ¹ -B ² -SO ₂ -, where B ¹ and B ² are as defined in .1. 143. The zinc binding ligand according to claim 1, where G ^B has the formula —B ¹ —B ² —C (O) - or —B ¹ —B ² —CH ₂ -, where B ¹ and B ² are as defined in .1. 144. The zinc binding ligand according to claim 1, where G ^B has the formula —B ¹ —B ² —C (O) - or —B ¹ —B ² —NH—, where B ¹ and B ² are as defined in 1. 145. The zinc-binding ligand according to claim 1, where G ^B has the formula —B ¹ -B ² -CH ₂ - or -B ¹ -B ² -SO ₂ -, where B ¹ and B ² are as defined in claim 1 . 146. The zinc binding ligand according to claim 1, wherein G ^B has the formula —B ¹ —B ² —NH— or —B ¹ —B ² —SO ₂ -, wherein B ¹ and B ² are as defined in claim 1. 147. The zinc-binding ligand according to claim 1, where G ^B has the formula —B ¹ -B ² -CH ₂ - or –B ¹ -B ² -NH-, where B ¹ and B ² are as defined in claim 1. 148. The zinc binding ligand according to claim 1, where G ^B has the formula —B ¹ —B ² —C (O) -. 149. The zinc-binding ligand according to claim 1, where G ⁱⁿ has the formula –B ¹ -B ² -CH ₂ -. 150. The zinc binding ligand according to claim 1, wherein G ^B has the formula —B ¹ —B ² —SO ₂ -. 151. The zinc-binding ligand according to claim 1, where G ^B has the formula –B ¹ -B ² -NH-. 152. The zinc binding ligand according to claim 1, wherein B ¹ is a valence bond, —O— or —S—. 153. The zinc binding ligand according to claim 1, wherein B ¹ is a valence bond, —O— or —N (R ⁶ ) -. 154. The zinc binding ligand according to claim 1, wherein B ¹ is a valence bond, —S— or —N (R ⁶ ) -. 155. The zinc binding ligand according to claim 1, wherein B ¹ is —O—, —S— or —N (R ⁶ ) -. 156. The zinc binding ligand according to claim 1, wherein B ¹ is a valence bond or —O—. 157. The zinc binding ligand according to claim 1, wherein B ¹ is a valence bond or —S—. 158. The zinc binding ligand according to claim 1, wherein B ¹ is a valence bond or —N (R ⁶ ) -. 159. The zinc binding ligand according to claim 1, wherein B ¹ is —O— or —S—. 160. The zinc binding ligand according to claim 1, wherein B ¹ is —O— or —N (R ⁶ ) -. 161. The zinc binding ligand according to claim 1, wherein B ¹ is —S— or —N (R ⁶ ) -. 162. The zinc binding ligand according to claim 1, wherein B ¹ is a valence bond. 163. The zinc binding ligand according to claim 1, wherein B ¹ is —O—. 164. The zinc binding ligand according to claim 1, wherein B ¹ is —S—. 165. The zinc binding ligand according to claim 1, wherein B ¹ is —N (R ⁶ ) -. 166. The zinc binding ligand according to claim 1, where B ² is a valence bond, C ₁ -C ₁₈ alkylene, C ₂ -C ₁₈ alkenylene, C ₂ -C ₁₈ alkynylene, arylene, heteroarylene, -C ₁ -C _18- alkylaryl-, -C (= O) -C ₁ -C ₁₈ -alkyl-С (= O) -, -С (= O) -С ₁ -С ₁₈ -alkyl-O-С ₁ -С ₁₈ - alkyl-C (= O) -, -C (= O) -C ₁ -C ₁₈ -alkyl-S-C ₁ -C ₁₈ -alkyl-C (= O) -, -C (= O) -C ₁ -C ₁₈ -alkyl-NR ⁶ -C ₁ -C ₁₈ -alkyl-C (= O) -; and alkylene and arylene fragments are optionally substituted as defined in claim 1. 167. The zinc binding ligand of claim 166, wherein B ² is a valence bond, C ₁ -C ₁₈ alkylene, C ₂ -C ₁₈ alkenylene, C ₂ -C ₁₈ alkynylene, arylene, heteroarylene, -C ₁ -C _18- alkylaryl-, -C (= O) -C ₁ -C ₁₈ -alkyl-C (= O) -, -C (= O) -C ₁ -C ₁₈ -alkyl-O-C ₁ -C ₁₈ - alkyl-C (= O) -, and fragments of alkylene and arylene are optionally substituted as defined in claim 1. 168. The zinc binding ligand according to Claim 167, wherein B ² is a valence bond, C ₁ -C ₁₈ alkylene, C ₂ -C ₁₈ alkenylene, C ₂ -C ₁₈ alkynylene, arylene, heteroarylene, -C ₁ -C _18- alkylaryl-, -C (= O) -C ₁ -C ₁₈ -alkyl-C (= O) -, and fragments of alkylene and arylene are optionally substituted as defined in claim 1. 169. The zinc binding ligand according to Claim 168, wherein B ² is a valence bond, C ₁ -C ₁₈ alkylene, arylene, heteroarylene, -C ₁ -C ₁₈ -alkylaryl, -C (= O) -C ₁ -C ₁₈ -alkyl-C (= O) -, and fragments of alkylene and arylene are optionally substituted as defined in claim 1. 170. The zinc binding ligand of claim 169, wherein B is a valence bond, C ₁ -C ₁₈ alkylene, arylene, heteroarylene, -C ₁ -C ₁₈ alkylaryl, and fragments of alkylene and arylene are optionally substituted as defined in .1. 171. The zinc binding ligand of claim 170, wherein B ² is a valence bond, C ₁ -C ₁₈ -alkylene, arylene, -C ₁ -C ₁₈ -alkylaryl, and fragments of alkylene and arylene are optionally substituted as defined in 1. 172. The zinc-binding ligand according to Claim 171, wherein B ² is a valence bond or —C ₁ -C ₁₈ alkylene, and alkylene moieties are optionally substituted as defined in claim 1. 173. The zinc binding ligand according to claim 1, wherein C consists of 0-5 neutral amino acids independently selected from the group consisting of Abz, Gly, Ala, Thr and Ser. 174. The zinc binding ligand according to Claim 173, wherein C is 0-5 Gly. 175. The zinc binding ligand of claim 174, wherein C is 0 Gly. 176. Zinc-binding ligand according to 174, where C consists of 1 Gly. 177. Zinc-binding ligand according to 174, where C consists of 2 Gly. 178. Zinc-binding ligand according to 174, where C consists of 3 Gly. 179. Zinc-binding ligand according to 174, where C consists of 4 Gly. 180. The zinc binding ligand according to Claim 174, wherein C is composed of 5 Gly. 181. The zinc binding ligand according to Claim 173, wherein C is -Abz- (Gly) _0-4 -. 182. The zinc-binding ligand according to claim 1, where D includes 1-16 positively charged groups. 183. The zinc binding ligand according to Claim 182, wherein D includes 1-12 positively charged groups. 184. The zinc binding ligand according to Claim 183, wherein D includes 1-10 positively charged groups. 185. The zinc binding ligand according to claim 1, wherein D is a fragment containing basic amino acids selected from the group consisting of Lys and Arg and their D isomers. 186. The zinc binding ligand of claim 185, wherein the basic amino acid is Arg. 187. The zinc binding ligand according to claim 1, wherein X is —OH or —NH ₂ . 188. The zinc binding ligand according to Claim 187, wherein X is —NH ₂ . 189. An insulin hexamer in the R state, comprising 6 insulin molecules, at least 2 zinc ions, and a zinc binding ligand according to any one of the preceding claims. 190. The insulin hexamer in the R state according to claim 189, wherein the insulin is selected from the group consisting of human insulin, its analogue, its derivative, and combinations of any of them. 191. The insulin hexamer in the R state according to claim 190, wherein the insulin is an analog of human insulin selected from the group consisting of v. an analogue where position B28 is Asp, Lys, Leu, Val or Ala, and position B29 is Lys or Pro; and vi. des (B28-B30), des (B27) or des (B30) human insulin. 192. The insulin hexamer in the R state according to Claim 191, wherein the insulin is an analog of human insulin, where position B28 is Asp or Lys, and position B29 is Lys or Pro. 193. The insulin hexamer in the R state according to Claim 191, wherein the insulin is des (B30) human insulin. 194. The insulin hexamer in the R state according to claim 190, wherein the insulin is a derivative of human insulin containing one or more lipophilic substituents. 195. The insulin hexamer in the R state according to claim 194, wherein the insulin derivative is selected from the group consisting of B29-Nε-myristoyl des (B30) human insulin, B29-Nε-palmitoyl des (B30) human insulin, B29- Nε-myristoyl of human insulin, B29-Nε-palmitoyl of human insulin, B28-Nε-myristoyl Lys ^B28 Pro ^B29 human insulin, B28-Nε-palmitoyl Lys ^B28 Pro ^B29 human insulin, B30-Nε-myristoyl-Thr ^B29 Lys ^B30 human insulin , B30-Nε -palmitoyl-Thr ^B29 Lys ^B30 human insulin, B29-Nε - (N-palmitoyl-γ-glutamyl) -des (B30) human insulin, B29-Nε - (N-lit. holil-γ-glutamyl) -des (B30) human insulin, B29-Nε - (ω -karboksigeptadekanoil) -des (B30) human insulin and B29-Nε - (ω -karboksigeptadekanoil) human insulin. 196. The insulin hexamer in the R state according to Claim 195, wherein the insulin derivative is B29-Nε-myristoyl des (B30) human insulin. 197. The insulin hexamer according to any one of claims 189-196, further comprising at least 3 phenolic molecules. 198. An aqueous insulin preparation comprising insulin hexamers in the R-state according to any one of claims 189-197. 199. A method of prolonging the action of an insulin preparation, which comprises adding a zinc-binding ligand according to any one of claims 1 to 188 to an insulin preparation. 200. The aqueous insulin preparation according to p, where the ratio between precipitated insulin and dissolved insulin is in the range from 99: 1 to 1:99. 201. The aqueous insulin preparation according to claim 200, where the ratio between precipitated insulin and dissolved insulin is in the range from 95: 5 to 5:95. 202. An aqueous insulin preparation according to claim 201, where the ratio between precipitated insulin and dissolved insulin is in the range from 80:20 to 20:80. 203. The aqueous insulin preparation according to claim 202, wherein the ratio between precipitated insulin and dissolved insulin is in the range from 70:30 to 30:70. 204. A method of producing a zinc-binding ligand according to claim 1, comprising the steps of identification of the starting compounds that are capable of displacing the ligand from His ^{B10 —} Zn ²⁺ site in the R state; optional attachment of a fragment consisting of 0-5 neutral α - or β-amino acids; the addition of a fragment comprising 1-20 positively charged groups independently selected from amino or guanidino groups.