Metal coordinated compositions

• US 20080015352A1
• Filed: 06/29/2007
• Published: 01/17/2008
• Est. Priority Date: 10/25/2004
• Status: Active Grant

• Current Assignee: Synthonics Incorporated (Synthonics Technologies, Inc.)
• Original Assignee: Synthonics Incorporated (Synthonics Technologies, Inc.)
• Inventors: Piccariello, Thomas
• Granted Patent: US 7,799,937 B2
• Time in Patent Office: Days
• US Class Current: 544/265
• CPC Class Codes: A61K 47/55 the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
• CPC Class Codes: C07C 229/76 Metal complexes of amino carboxylic acids
• CPC Class Codes: C07C 237/22 having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated peptides C07K
• CPC Class Codes: C07C 245/08 with the two nitrogen atoms of azo groups bound to carbon atoms of six-membered aromatic rings, e.g. azobenzene
• CPC Class Codes: C07C 259/06 having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
• CPC Class Codes: C07C 279/14 being further substituted by carboxyl groups
• CPC Class Codes: C07C 279/26 X and Y being nitrogen atoms, i.e. biguanides
• CPC Class Codes: C07D 285/28 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached in position 3
• CPC Class Codes: C07D 307/14 Radicals substituted by nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 473/18 one oxygen and one nitrogen atom, e.g. guanine
• CPC Class Codes: C07D 473/38 attached in position 6
• CPC Class Codes: C07D 489/08 Oxygen atom
• CPC Class Codes: C07F 17/00 Metallocenes

Abstract

A metal coordination complex of a biologically active moiety and a metal is disclosed. The complex confers to the biologically active moiety an improved performance which can include potency, stability, absorbability, targeted delivery, and combinations thereof.

Claims

1-36. -36. (canceled)

37. A metal coordination complex, comprising:

a biologically active moiety and

a metal atom,

wherein the biologically active moiety comprises a first functional group having a heteroatom and second functional group having a heteroatom,

wherein the first functional group and the second functional group are capable of forming a metal coordination bond,

wherein the first functional group and the second functional group are in a spatial relationship such that the first functional group and the second functional group are capable of participating in the formation of a stable chelate with the metal atom, and

wherein the biologically active moiety is not DOPA, acycloguanosine, or tetracycline antibiotics.

38. The metal coordination complex of claim 37, wherein the biologically active moiety is selected from the group consisting of Acetalzolamide, Vorinostat, Aliskiren, Alvimopan, Bicalutamide, Baclofen, Balsalzide, Brinzolamide, Chlorproguanil, Diclofenac, Dorzolamide, Droxidopa, Clonixin, Ebrotidine, Enfenamic acid, Ethylmethylthambutene, Etodolac, Flufenamic acid, Fosfosal, Lazabemide, Mefenamic acid, 6-Mercaptopurine, Melagatran, Mycopheolate mofetil, Pregabalin, Quinocide, Rilmazafone, Tafenoquine, Tilarginine, Tolfenamic acid, Cidofovir, Didanosine, Dideoxyadenosine, Etidronic acid, Moroxydine, Nelfinavir, Pamidronic acid, Risedronic acid, and Zoledronic acid.

39. The metal coordination complex of claim 37, wherein the metal coordination bond forms a 4 to 8 atom ring encompassing the metal atom, the first functional group, and the second functional group.

40. The metal coordination complex of claim 39, wherein the 4 to 8 atom ring is free of trans double bonds.

41. The metal coordination complex of claim 37, wherein at least one of the heteroatoms is selected from the group consisting of oxygen and sulfur when the metal atom is selected from the group consisting of magnesium and calcium.

42. The metal coordination complex of claim 37, wherein the first functional group comprises a heteroatom selected from the group consisting of nitrogen and sulfur.

43. The metal coordination complex of claim 37, wherein the first functional group and the second functional group comprise a heteroatom selected from the group consisting of nitrogen and sulfur.

44. The metal coordination complex of claim 37, wherein the heteroatom is selected from the group consisting of oxygen, sulfur, and nitrogen.

45. The metal coordination complex of claim 37, wherein the metal atom is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, zinc, vanadium, chromium, cobalt, nickel, and copper.

46. A metal coordination complex, comprising:

a biologically active moiety and

a metal atom,

wherein the biologically active moiety comprises a first protonated heteroatom and a second protonated heteroatom,

wherein the biologically active moiety has a pK_a of approximately equal to water or lower than water,

wherein the first protonated heteroatom and the second protonated heteroatom are in a spatial relationship such that the first protonated heteroatom and the second protonated heteroatom are capable of participating in the formation of a stable chelate with the metal atom, and

wherein the biologically active moiety is not DOPA, acycloguanosine, or tetracycline antibiotics.

47. The metal coordination complex of claim 46, wherein the metal atom is selected from the group consisting of transition metals, p-block metals, and s-block metals.

48. The metal coordination complex of claim 46, wherein the metal atom is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, zinc, vanadium, chromium, cobalt, nickel, and copper.

49. The metal coordination complex of claim 46, wherein the biologically active moiety is selected from the group consisting of Acetalzolamide, Vorinostat, Aliskiren, Alvimopan, Bicalutamide, Baclofen, Balsalzide, Brinzolamide, Chlorproguanil, Diclofenac, Dorzolamide, Droxidopa, Clonixin, Ebrotidine, Enfenamic acid, Ethylmethylthambutene, Etodolac, Flufenamic acid, Fosfosal, Lazabemide, Mefenamic acid, 6-Mercaptopurine, Melagatran, Mycopheolate mofetil, Pregabalin, Quinocide, Rilmazafone, Tafenoquine, Tilarginine, Tolfenamic acid, Cidofovir, Didanosine, Dideoxyadenosine, Etidronic acid, Moroxydine, Nelfinavir, Pamidronic acid, Risedronic acid, and Zoledronic acid.

50. A method of modulating the properties of a biologically active moiety, comprising:

forming a metal coordination complex with the biologically active moiety and a metal atom,

wherein the biologically active moiety comprises a first functional group having a heteroatom and second functional group having a heteroatom,

wherein the first functional group and the second functional group are capable of forming a metal coordination bond,

wherein the first functional group and the second functional group are in a spatial relationship such that the first functional group and the second functional group are capable of participating in the formation of a stable chelate with the metal atom, and

wherein the biologically active moiety is not DOPA, acycloguanosine, or tetracycline antibiotics.

51. The method of claim 50, wherein the metal atom is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, zinc, vanadium, chromium, cobalt, nickel, and copper.

52. The method of claim 50, wherein the biologically active moiety is selected from the group consisting of Acetalzolamide, Vorinostat, Aliskiren, Alvimopan, Bicalutamide, Baclofen, Balsalzide, Brinzolamide, Chlorproguanil, Diclofenac, Dorzolamide, Droxidopa, Clonixin, Ebrotidine, Enfenamic acid, Ethylmethylthambutene, Etodolac, Flufenamic acid, Fosfosal, Lazabemide, Mefenamic acid, 6-Mercaptopurine, Melagatran, Mycopheolate mofetil, Pregabalin, Quinocide, Rilmazafone, Tafenoquine, Tilarginine, Tolfenamic acid, Cidofovir, Didanosine, Dideoxyadenosine, Etidronic acid, Moroxydine, Nelfinavir, Pamidronic acid, Risedronic acid, and Zoledronic acid.

53. A method of claim 50, further comprising

adding an adjuvant selected from the group consisting of amino acids, peptides, carbohydrates and lipids that confer desired performance parameters to the biologically active moiety.

54. The method of claim 50, wherein the properties to be modulated are selected from the group consisting of potency, stability, absorbability, targeted delivery, and combinations thereof.

55. A method of modulating the properties of a biologically active moiety, comprising:

forming a metal coordination complex with the biologically active moiety and a metal atom,

wherein the biologically active moiety comprises a first functional group having a heteroatom and second functional group having a heteroatom,

wherein the first functional group and the second functional group are capable of participating in the formation of a metal coordination bond,

wherein the first functional group and the second functional group are in a spatial relationship such that the first functional group and the second functional group are capable of participating in the formation of a stable chelate with the metal atom,

wherein the biologically active moiety is selected from the group consisting of Acetalzolamide, Vorinostat, Aliskiren, Alvimopan, Bicalutamide, Baclofen, Balsalzide, Brinzolamide, Chlorproguanil, Diclofenac, Dorzolamide, Droxidopa, Clonixin, Ebrotidine, Enfenamic acid, Ethylmethylthambutene, Etodolac, Flufenamic acid, Fosfosal, Lazabemide, Mefenamic acid, 6-Mercaptopurine, Melagatran, Mycopheolate mofetil, Pregabalin, Quinocide, Rilmazafone, Tafenoquine, Tilarginine, Tolfenamic acid, Cidofovir, Didanosine, Dideoxyadenosine, Etidronic acid, Moroxydine, Nelfinavir, Pamidronic acid, Risedronic acid, and Zoledronic acid, and

wherein the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, zinc, vanadium, chromium, cobalt, nickel, and copper.

56. A method of claim 55, further comprising

adding an adjuvant selected from the group consisting of amino acids, peptides, carbohydrates, and lipids that confer desired performance parameters to the biologically active moiety.

57. The method of claim 55, wherein the properties to be modulated are selected from the group consisting of potency, stability, absorbability, targeted delivery, and combinations thereof.