Substituted carbamate compounds

Patent metadata

Field	Value
Publication number	US-9388172-B2
Application number	US-201514707524-A
Country	US
Kind code	B2
Filing date	May 8, 2015
Priority date	Nov 8, 2012
Publication date	Jul 12, 2016
Grant date	Jul 12, 2016

Abstract

The invention is concerned with the compounds of formula (I):

and pharmaceutically acceptable salts thereof. In addition, the present invention relates to methods of manufacturing and using the compounds of formula (I) as well as pharmaceutical compositions containing such compounds. The compounds of formula (I) are antagonists of the TRPA1 channel and may be useful in treating inflammatory diseases and disorders associated with that channel.

First claim

The invention claimed is:

1. A compound of formula (I):

wherein:
X is —CH 2 — or oxygen; and
R1 is benzoimidazolyl, benzimidazole ring substituted with a halogen, benzooxazolyl, benzoxazole ring substituted with a halogen, an unsubstituted 5-membered heteroaryl ring or a 5-membered heteroaryl ring substituted with halo-phenyl, methyl-pyridinyl or halo-pyridinyl, or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein X is —CH 2 —.

3. The compound according to claim 1 , wherein said 5-membered heteroaryl ring is imidazolyl, oxazolyl or oxadiazolyl.

4. The compound according to claim 1 , wherein said halo moiety is fluorine or chlorine.

5. The compound according to claim 1 , wherein said compound is:
5-Chloro-2-{3,3,3-trifluoro-2-[3-(3-trifluoromethylphenyl)-piperidin-1-ylmethyl]-propyl}-1H-benzoimidazole hydrochloride;
1-{2-[5-(4-Chlorophenyl)-1H-imidazol-2-ylmethyl]-3,3,3-trifluoropropyl}-3-(3-trifluoromethyl-phenyl)piperidine hydrochloride;
1-{2-[5-(4-Chlorophenyl)-[1,3,4]oxadiazol-2-ylmethyl]-3,3,3-trifluoropropyl}-3-(3-trifluoromethylphenyl)-piperidine hydrochloride;
6-Chloro-2-{3,3,3-trifluoro-2-[3-(3-trifluoromethylphenyl)-piperidin-1-ylmethyl]-propyl}-benzooxazole hydrochloride;
3-(3-Trifluoromethylphenyl)-1-[3,3,3-trifluoro-2-(5-phenyl-1H-imidazol-2-ylmethyl)-propyl]-piperidine hydrochloride;
1-{2-[5-(3-Chlorophenyl)-1H-imidazol-2-ylmethyl]-3,3,3-trifluoropropyl}-3-(3-trifluoromethyl-phenyl)piperidine hydrochloride;
1-{3,3,3-Trifluoro-2-[5-(4-fluorophenyl)-1H-imidazol-2-ylmethyl]-propyl}-3-(3-trifluoromethylphenyl)-piperidine hydrochloride;
1-{3,3,3-Trifluoro-2-[5-(4-fluorophenyl)-[1,3,4]oxadiazol-2-ylmethyl]-propyl}-3-(3-trifluoromethylphenyl)-piperidine hydrochloride;
1-{2-[5-(3-Chlorophenyl)-[1,3,4]oxadiazol-2-ylmethyl]-3,3,3-trifluoro-propyl}-3-(3-trifluoromethylphenyl)-piperidine hydrochloride;
2-Methyl-5-(5-{3,3,3-trifluoro-2-[3-(3-trifluoromethylphenyl)-piperidin-1-ylmethyl]-propyl}-[1,3,4]oxadiazol-2-yl)-pyridine;
5-Chloro-2-(5-{3,3,3-trifluoro-2-[3-(3-trifluoromethylphenyl)-piperidin-1-ylmethyl]-propyl}-[1,3,4]oxadiazol-2-yl)-pyridine hydrochloride;
4-{3,3,3-Trifluoro-2-[5-(4-fluoro-phenyl)-[1,3,4]oxadiazol-2-ylmethyl]-propyl}-2-(3-trifluoromethylphenyl)-morpholine hydrochloride;
1-{2-[5-(4-Chlorophenyl)-oxazol-2-ylmethyl]-3,3,3-trifluoro-propyl}-3-(3-trifluoromethyl-phenyl)-piperidine hydrochloride;
1-{2-[3-(4-Chlorophenyl)-[1,2,4]oxadiazol-5-ylmethyl]-3,3,3-trifluoropropyl}-3-(3-trifluoromethylphenyl)-piperidine hydrochloride;
1-{3,3,3-Trifluoro-2-[5-(4-fluoro-phenyl)-[1,2,4]oxadiazol-3-ylmethyl]-propyl}-3-(3-trifluoromethylphenyl)-piperidine hydrochloride;
4-{2-[5-(4-Chlorophenyl)-[1,3,4]oxadiazol-2-ylmethyl]-3,3,3-trifluoropropyl}-2-(3-trifluoromethylphenyl)-morpholine hydrochloride;
4-{3,3,3-Trifluoro-2-[5-(4-fluorophenyl)-[1,3,4]oxadiazol-2-ylmethyl]-propyl}-2-(4-trifluoromethylphenyl)-morpholine hydrochloride; or
4-{2-[5-(4-Chlorophenyl)-[1,3,4]oxadiazol-2-ylmethyl]-3,3,3-trifluoropropyl}-2-(4-trifluoromethylphenyl)-morpholinehydrochloride.

6. A pharmaceutical composition, comprising a therapeutically effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier.

7. A method of treating a respiratory disorder mediated by TRPA1, the method comprising administering a therapeutically effective amount of a compound according to claim 1 to a subject in need thereof.

8. The method of claim 7 , wherein the respiratory disorder is selected from the group consisting of chronic obstructive pulmonary disorder (COPD), asthma, allergic rhinitis, and bronchospasm.

Assignees

• Hoffmann La Roche

Inventors

• Brotherton-Pleiss Christine E
• Erickson Shawn David
• Li Hongju
• So Sung-Sau

Classifications

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P11/02

  Nasal agents, e.g. decongestants · CPC title

• A61P11/06

  Antiasthmatics · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• C07D413/06 Primary

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