Salt of (R)-3-(6-amino-pyridin-3-yl)-2-(1-Cyclohexyl-1H-imidazol-4-yl) ethyl propionate

Patent metadata

Field	Value
Publication number	US-9156815-B2
Application number	US-201214359737-A
Country	US
Kind code	B2
Filing date	Nov 22, 2012
Priority date	Nov 25, 2011
Publication date	Oct 13, 2015
Grant date	Oct 13, 2015

Abstract

The invention relates to the salt of naphthalene-1,5-disulfonic acid with (R)-3-(6-amino-pyridin-3-yl)-2-(1-cyclohexyl-1H-imidazol-4-yl)ethyl propionate, which can be represented by the following structural formula of formula (I), to methods for the production thereof, to drugs containing said salt, and to the use of said drugs to treat diseases that are accompanied by thromboses, embolisms, hypercoagulability, or fibrotic changes.

First claim

What is claimed:

1. A salt of formula (I)

wherein n has a value from 0.5 to 1.8 and indicates the molar ratio of (R)-3-(6-aminopyridin-3-yl)-2-(1-cyclohexyl-1H-imidazol-4-yl)propionic acid ethyl ester to naphthalene-1,5-disulfonic acid, wherein
the salt of formula (I) exhibits an XRPD measured with CuKα radiation at the angular positions having reflections at the following 2 theta values: 7.35; 11.4; 13.69; 14.96; 17.49; 19.3 and 22.48 in each case ±0.2 degrees 2 theta.

2. The salt of formula (I) as claimed in claim 1 , wherein the XRPD measured with CuKα radiation has reflections that are essentially identical to those shown in FIG. 1 .

3. The salt of formula (I) as claimed in claim 1 , wherein the Raman spectrum has characteristic bands at the following wavelengths [cm −1 ]: 2936; 1570; 1401; 1352; 998 and 856, in each case ±2 cm −1 .

4. A method for the production of the salt as claimed in claim 1 , the method comprising:
dissolving naphthalene-1,5-disulfonic acid in a solvent A;
adding a solution of (R)-3-(6-aminopyridin-3-yl)-2-(1-cyclohexyl-1H-imidazol-4-yl)propionic acid ethyl ester in a solvent B;
obtaining the naphthalene-1,5-disulfonic acid salt of (R)-3-(6-aminopyridin-3-yl)-2-(1-cyclohexyl-1H-imidazol-4-yl)propionic acid ethyl ester of formula (I); and
optionally partially or completely removing the solvents.

5. The method of claim 4 , wherein the solvents A and B are the same or different, and are selected from the group consisting of ethanol, acetone, methyl ethyl ketone, acetonitrile, tetrahydrofuran, dimethyl sulfoxide, dimethylformamide, N-methylpyrrolidinone, methanol, propanol, butanol and water.

6. A pharmaceutical composition comprising a salt as claimed in claim 1 and a pharmaceutically suitable and physiologically compatible carrier substance, additive and/or auxiliary.

7. The salt of formula (I) as claimed in claim 2 , wherein the Raman spectrum has characteristic bands at the following wavelengths [cm −1 ]: 2936; 1570; 1401; 1352; 998 and 856, in each case ±2 cm −1 .

8. A pharmaceutical composition comprising a salt as claimed in claim 2 and a pharmaceutically suitable and physiologically compatible carrier substance, additive and/or auxiliary.

9. A pharmaceutical composition comprising a salt as claimed in claim 3 and a pharmaceutically suitable and physiologically compatible carrier substance, additive and/or auxiliary.

10. A pharmaceutical composition comprising a salt as claimed in claim 7 and a pharmaceutically suitable and physiologically compatible carrier substance, additive and/or auxiliary.

Assignees

• Sanofi Sa

Inventors

• Rossen Kai
• Wehlan Hermut

Classifications

• C07D401/06 Primary

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07C309/35

  Naphthalene sulfonic acids · CPC title

• A61K31/4439

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title