CYCLITOLS AND THEIR DERIVATIVES AND THEIR THERAPEUTIC APPLICATIONS

• US 20140171394A1
• Filed: 12/09/2013
• Published: 06/19/2014
• Est. Priority Date: 12/29/2006
• Status: Abandoned Application

• Current Assignee: Universite De Strasbourg (Financière Meeschaert SA)
• Original Assignee: Universite De Strasbourg (Financière Meeschaert SA), NormOxys, Inc.
• Inventors: Lehn, Jean-Marie, Pothukanuri, Srinivasu, Koumbis, Alexandros, Duarte, Carolina, Nicolau, Claude
• Application Number:
  US14/100,641
• Publication Number:
  US 20140171394A1
• Time in Patent Office: Days
• US Class Current: 514/105
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07F 9/093 Polyol derivatives esterified at least twice by phosphoric acid groups
• CPC Class Codes: C07F 9/144 with cycloaliphatic alcohols
• CPC Class Codes: C07F 9/6561 containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
• CPC Class Codes: C07F 9/65744 condensed with carbocyclic or heterocyclic rings or ring systems
• CPC Class Codes: C07F 9/65746 the molecule containing more than one cyclic phosphorus atom

Abstract

The present invention is directed to polyphosphorylated and pyrophosphate derivatives of cyclitols. More particularly, the invention relates to polyphosphorylated and pyrophosphate derivatives of inositols. The invention also relates to compositions of the polyphosphorylated and pyrophosphate derivatives of inositol and other similar, more lipophilic derivatives, and their use as allosteric effectors, cell-signaling molecule analogs, and therapeutic agents.

Claims

1-31. -31. (canceled)

32. A composition comprising a pyrophosphate inositol which reduces hemoglobin'"'"'s oxygen affinity, wherein:

the pyrophosphate is an internal pyrophosphate;

the inositol is cis-inositol, epi-inositol, allo-inositol, muco-inositol, neo-inositol, scyllo-inositol, (+) chiro-inositol, or (−

) chiro-inositol, and wherein the pyrophosphate inositol is monopyrophosphate, bispyrophosphate, or trispyrophosphate; and

the pyrophosphate inositol comprises a derivatized hydroxyl selected from alkoxy (—

OR) or acyloxy (—

OCOR),

where R is selected from alkyl, aryl, acyl, aralkyl, alkenyl, alkynyl, heterocyclyl, polycyclyl, carbocycle, amino, acylamino, amido, alkylthio, sulfonate, alkoxyl, or sulfoxido, or a salt thereof.

33. The composition of claim 32, wherein the pyrophosphate inositol is complexed with a cation to form a salt, and wherein the cation is an alkali metal cation, an alkaline metal cation, an ammonium, or an organic cation.

34. The composition of claim 32, wherein R is a lower alkyl.

35. The composition of claim 34, where R is methyl.

36. The composition of claim 32, wherein the inositol is scyllo-inositol.

37. The composition of claim 32, wherein the inositol is monopyrophosphate.

38. The composition of claim 32, wherein the inositol is bispyrophosphate.

39. A pharmaceutical composition, comprising a pyrophosphate inositol wherein:

the pyrophosphate is an internal pyrophosphate;

the inositol is cis-inositol, epi-inositol, allo-inositol, muco-inositol, neo-inositol, scyllo-inositol, (+) chiro-inositol, or (−

) chiro-inositol, and wherein the pyrophosphate inositol is monopyrophosphate, bispyrophosphate, or trispyrophosphate; and

the pyrophosphate inositol comprises a derivatized hydroxyl selected from alkoxy (—

OR) or acyloxy (—

OCOR),

where R is selected from alkyl, aryl, acyl, aralkyl, alkenyl, alkynyl, heterocyclyl, carbocycle, amino, acylamino, amido, alkylthio, sulfonate, alkoxyl, or a salt selected from an alkali metal cation, an alkaline metal cation, ammonium, or an organic cation.

40. The pharmaceutical composition of claim 39, wherein R is a lower alkyl.

41. The pharmaceutical composition of claim 40, where R is methyl.

42. The pharmaceutical composition of claim 39, wherein the inositol is scyllo-inositol.

43. The pharmaceutical composition of claim 39, wherein the inositol is monopyrophosphate.

44. The pharmaceutical composition of claim 39, wherein the inositol is bispyrophosphate.

45. A method of treating an ischemia mediated disease comprising administering to a patient with an ischemic disease a therapeutically effective amount of the pharmaceutical composition of claim 39.

46. The method of claim 45, where in the ischemia mediated disease is one of Alzheimer'"'"'s disease, dementia, stroke, chronic obstructive pulmonary disease (COPD), osteoporosis, and adult respiratory distress syndrome (ARDS).