4-[4-(amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide monohydrate

• US 20100173953A1
• Filed: 09/29/2007
• Published: 07/08/2010
• Est. Priority Date: 10/11/2006
• Status: Active Grant

• Current Assignee: Bayer Intellectual Property GmbH (Bayer AG)
• Original Assignee: Bayer Intellectual Property GmbH (Bayer AG)
• Inventors: Stiehl, Juergen, Grunenberg, Alfons, Keil, Birgit, Tenbieg, Katharina
• Granted Patent: US 9,957,232 B2
• Time in Patent Office: Days
• US Class Current: 514/350
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 17/06 Antipsoriatics
• 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 213/62 Oxygen or sulfur atoms
• CPC Class Codes: C07D 213/78 Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 213/81 Amides; Imides

Abstract

The present invention relates to 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide monohydrate, to processes for its preparation, to pharmaceutical compositions comprising it and to its use in the control of disorders.

Claims

1. A compound of the formula (II)

2. The compound of claim 1 which shows in the X-ray diffractometry a peak maximum of the 2 Theta angel of 21.2.

3. The compound of claim 1 which shows in the FIR spectrum a peak maximum of 353 cm⁻

1.

4. A process for the preparation of the compound of the formula (II) of claim 1 which comprises dissolution of 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide and adding water until precipitation.

5. The preparation of the compound of the formula (II) of claim 1 which comprises suspension of 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide in an aqueous solvent and then stirring or shaking until conversion to the compound of the formula (II).

6. A compound of the formula (II) of claim 1 for the treatment of hyper-proliferative disorders.

7. A compound of the formula (II) of claim 1 for the treatment of solid tumors, lymphomas, sarcomas, leukemias, cancers of the breast, respiratory tract, brain, reproductive organs, digestive tract, urinary tract, eye, liver, skin, head and neck, thyroid and/or parathyroid.

8. A use of the compound of the formula (II) of claim 1 for the preparation of a pharmaceutical composition for the treatment of hyper-proliferative disorders.

9. The use of claim 8 for the treatment of solid tumors, lymphomas, sarcomas, leukemias, cancers of the breast, respiratory tract, brain, reproductive organs, digestive tract, urinary tract, eye, liver, skin, head and neck, thyroid and/or parathyroid.

10. A pharmaceutical composition comprising the compound of the formula (II) of claim 1 mainly, no significant fractions of another form of 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide and one or more inert, nontoxic, pharmaceutically suitable excipients.

11. The pharmaceutical composition of claim 10 containing more than 90 percent by weight of the compound of the formula (II) related to the total amount of the compound of the formula (II) present in the composition.

12. The pharmaceutical composition of claim 10 for the treatment of disorders.

13. A method for treating hyper-proliferative disorders using an effective amount of the compound of the formula (II) of claim 1 or of a pharmaceutical composition as defined in one of claims 10 to 12.

14. A combination comprising the compound of the formula (II) of claim 1 and one or more other pharmaceutical agents.

15. The combination of claim 14 wherein the one or more other pharmaceutical agents are cytotoxic agents, signal transduction inhibitors, anti-cancer agents, or antiemetics.

16. The pharmaceutical composition of claim 10 comprising one or more other pharmaceutical agents.

17. The pharmaceutical composition of claim 16 wherein the one or more other pharmaceutical agents are anti-hyper-proliferative agents, cytotoxic agents, signal transduction inhibitors, anti-cancer agents and/or antiemetics.