Inositol derivatives for use in pathological crystallization

Patent metadata

Field	Value
Publication number	US-10624909-B2
Application number	US-201616060980-A
Country	US
Kind code	B2
Filing date	Dec 12, 2016
Priority date	Dec 11, 2015
Publication date	Apr 21, 2020
Grant date	Apr 21, 2020

Abstract

The present invention relates to inositol derivatives covalently modified with one, two or three solubility functions, particularly polyethylene glycol moieties, for use in therapy or prevention of conditions related to pathological calcium crystallization, such as cardiovascular calcifications, nephrocalcinosis, calcinosis cutis, chondrocalcinosis and kidney stones.

First claim

The invention claimed is:

1. A method for treatment of a condition related to pathological calcium crystallization, comprising administering to a subject in need thereof a compound described by a general formula (II)

wherein
one or two or three X are R 1 and the remaining X independently from each other are selected from OPO 3 2− , OPSO 2 2− , and OSO 3 − ; and
each R 1 independently of any other R 1 is a polyethylene glycol or a polyglycerola.

2. The method for treatment of a condition related to pathological calcium crystallization according to claim 1 , wherein R 1 has a molar mass between 100 g/mol and 3000 g/mol.

3. The method for treatment of a condition related to pathological calcium crystallization according to claim 1 , wherein the compound is characterized by a general formula III a, III b, III c or III d:

wherein each X (independently) and R 1 have the meaning outlined above.

4. The method for treatment of a condition related to pathological calcium crystallization according to claim 1 , wherein more than one R 1 is present and each R 1 is the same as any other R 1 .

5. The method for treatment of a condition related to pathological calcium crystallization according to claim 1 , wherein the compound is characterized by a general formula (IV a), (IV b), (IV c), (IV d), (V a) or (V b)

wherein each X (independently) and R 1 have the meaning outlined above.

6. The method for treatment of a condition related to pathological calcium crystallization according to claim 1 , wherein one or two or three X are R 1 and the remaining X are
all OPO 3 2− or
all OPSO 2 2− or
all OSO 3 − .

7. The method for treatment of a condition related to pathological calcium crystallization according to claim 1 , wherein
one or two or three X are R 1 and the remaining X are OPO 3 2− ; and
R 1 is a polyethylene glycol and has a molar mass between 100 g/mol and 3000 g/mol.

8. The method for treatment of a condition related to pathological calcium crystallization according to claim 1 , wherein
one or two or three X are R 1 and the remaining X are OPSO 2 2− ; and
R 1 is a polyethylene glycol and has a molar mass between 100 g/mol and 3000 g/mol.

9. The method for treatment of a condition related to pathological calcium crystallization according to claim 1 , wherein two X are R 1 .

10. The method according to claim 1 , wherein:
one X is R 1 and of the remaining X
three X are OSO 3 − and two X are OPSO 2 2− , or three X are OSO 3 − and two X are OPO 3 2− , and
R 1 is a polyethylene glycol and has a molar mass between 100 g/mol and 3000 g/mol.

11. The method for treatment of a condition related to pathological calcium crystallization according to claim 1 , wherein R 1 is a polyethylene glycol characterized by a formula R 3 —(O—CH 2 —CH 2 ) n — or R 3 —(O—CH 2 —CH 2 ) n —O— and R 3 is hydrogen, methyl or ethyl.

12. The method for treatment of a condition related to pathological calcium crystallization according to claim 1 , wherein the compound is described by a general formula (III k), (III l), (III m), (III n), (IV e) or (V c)

wherein n has a value from 2 to 200.

13. The method for treatment of a condition related to pathological calcium crystallization according to claim 1 , wherein the compound is described by any one of formulae (III o), (III p), (III q), (III r), (III s), (III t), (III u), (III v), (III w), (III x), (III y), (III z), (IV f), (IV g), (IV h), (IV i), (IV j), (IV k), (V d), (V e), (V f), (V g), (V h) or (V i)

14. The method according to claim 1 , wherein said polyethylene glycol is a monodisperse polyethylene glycol.

15. The method according to claim 1 , wherein the compound is described by any one of formulae (III o), (III p), (III q), (III u), (III v) or (III w)

16. A compound described by a general formula (II)

wherein
two X are R 1 and the remaining X independently from each other X are selected from OPO 3 2− , OPSO 2 2− , and OSO 3 − ; and
each R 1 independently of any other R 1 is a polyethylene glycol or a polyglycerol.

17. The compound according to claim 16 , wherein the compound is described by any one of formulae

wherein each X (independently) and R 1 have the meaning outlined above.

18. The compound according to claim 16 , described by the formula

wherein n has a value from 2 to 200, particularly n is 2 or n is 7 to 50, more particularly n is 2, 7 to 12 or 40 to 50, even more particularly n is 2, 7, 9, 11 or 45.

19. The compound according to claim 16 , described by any one of formulae

20. A compound described by any one of formulae

Assignees

• Eth Zuerich
• Univ Bern

Inventors

• Ivarsson Mattias
• Castagner Bastien
• Leroux Jean-Christophe
• Pasch Andreas

Classifications

• A61K31/6615 Primary

  Compounds having two or more esterified phosphorus acid groups, e.g. inositol triphosphate, phytic acid · CPC title

• A61P13/12

  of the kidneys · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P9/14

  Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers · CPC title

• A61K47/60 Primary

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title