Pyridine derivatives

Patent metadata

Field	Value
Publication number	US-11117903-B2
Application number	US-201916722592-A
Country	US
Kind code	B2
Filing date	Dec 20, 2019
Priority date	Jun 20, 2017
Publication date	Sep 14, 2021
Grant date	Sep 14, 2021

Abstract

The invention relates to compound of formula (I)wherein R1 to R3 are as defined in the description and in the claims. The compound of formula (I) can be used as a medicament.

First claim

The invention claimed is:

1. A compound selected from the group consisting of:
5-(cyclopropylmethoxy)-4-(2,4-dichlorophenyl)-N-[(2S)-1-hydroxy-4-methylpentan-2-yl]pyridine-2-carboxamide;
4-(4-chlorophenyl)-5-(cyclopropylmethoxy)-N-[(1R,2S)-2-hydroxycyclohexyl]pyridine-2-carboxamide;
4-(4-chlorophenyl)-5-(cyclopropylmethoxy)-N-[(1S,2R)-2-hydroxycyclohexyl]pyridine-2-carboxamide;
methyl 2-[[4-(4-chlorophenyl)-5-(cyclopropylmethoxy)pyridine-2-carbonyl]amino]-2-ethylbutanoate;
methyl 2-[[5-(cyclopropylmethoxy)-4-(3,4-dichlorophenyl)pyridine-2-carbonyl]amino]-2-ethylbutanoate;
4-(4-chlorophenyl)-5-(cyclopropylmethoxy)-N-[(1R,2S)-2-methoxycyclohexyl]pyridine-2-carboxamide;
5-chloro-4-(cyclopropylmethoxy)-N-[(1R)-2-hydroxy-1-phenylethyl]pyridine-2-carboxamide;
5-chloro-4-(cyclopropylmethoxy)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]pyridine-2-carboxamide;
5-chloro-4-(cyclopropylmethoxy)-N-[(2S)-4-methyl-1-(methylamino)-1-oxopentan-2-yl]pyridine-2-carboxamide;
5-chloro-4-(cyclopropylmethoxy)-N-[(2R)-4-methyl-1-(methylamino)-1-oxopentan-2-yl]pyridine-2-carboxamide;
5-cyclopropyl-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-4-[(3-methyloxetan-3-yl)methoxy]pyridine-2-carboxamide;
6-[6-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-4-(cyclopropylmethoxy)pyri din-3-yl]-2-oxa-6-azaspiro [3 0.3]heptane;
tert-butyl (2S)-24[2-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-5-cyclopropylpyridin-4-yl]oxymethyl]pyrrolidine-1-carboxylate;
tert-butyl (3R)-3-[2-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-5-cyclopropylpyridin-4-yl]oxypyrrolidine-1-carboxylate;
5-tert-butyl-3-[5-cyclopropyl-4-[(3-methylsulfonylphenyl)methoxy]pyridin-2-yl]-1,2,4-oxadiazole;
N-[1-(azetidin-3-yl)-1-(5-methyl-1,3,4-oxadiazol-2-yl)ethyl]-5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridine-2-carboxamide;
ethyl 2-[[5-cyclopropyl-4-[(3-methyloxetan-3-yl)methoxy]pyridine-2-carbonyl]amino]-2-ethylbutanoate;
5-chloro-N-[1-cyclopropyl-2-(5-methyl-1,2,4-oxadiazol-3-yl)propan-2-yl]-4-[(2,2-difluoro-1-methylcyclopropyl)methoxy]pyridine-2-carboxamide;
4-(benzotriazol-1-yloxy)-N-[1-cyclopropyl-2-(5-methyl-1,2,4-oxadiazol-3-yl)propan-2-yl]-5-(trifluoromethyl)pyridine-2-carboxamide;
N-(4-amino-2-cyclopropyl-4-oxobutan-2-yl)-5-cyclopropyl-4-[(5-fluoropyridin-2-yl)methoxy]pyridine-2-carboxamide; and
N-[(2S)-1-cyclopropyl-2-(5-methyl-1,2,4-oxadiazol 01-3-yl)propan-2-yl]-4-(6-fluoropyridin-3-yl)-5-phenylmethoxypyridine-2-carboxamide;
or a pharmaceutically acceptable salt thereof.

2. A compound selected from the group consisting of:
5-(cyclopropylmethoxy)-4-(2,4-dichlorophenyl)-N-[(2S)-1-hydroxy-4-methylpentan-2-yl]pyridine-2-carboxamide;
methyl 2-[[5-(cyclopropylmethoxy)-4-(3,4-dichlorophenyl)pyridine-2-carbonyl]amino]-2-ethylbutanoate;
5-chloro-4-(cyclopropylmethoxy)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]pyridine-2-carboxamide;
5-cyclopropyl-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-4-[(3-methyloxetan-3-yl)methoxy]pyridine-2-carboxamide; and
N-(4-amino-2-cyclopropyl-4-oxobutan-2-yl)-5-cyclopropyl-4-[(5-fluoropyridin-2-yl)methoxy]pyridine-2-carboxamide;
or a pharmaceutically acceptable salt thereof.

3. A pharmaceutical composition comprising a compound in accordance with claim 1 , or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.

4. A method for the treatment of pain, neuropathic pain, asthma, osteoporosis, inflammation, psychiatric diseases, psychosis, oncology, encephalitis, malaria, allergy, immunological disorders, arthritis, gastrointestinal disorders, psychiatric disorders rheumatoid arthritis, psychosis or allergy, which method comprises administering an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, to a patient in need thereof.

5. A pharmaceutical composition comprising a compound in accordance with claim 2 , or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.

6. A method for the treatment of pain, neuropathic pain, asthma, osteoporosis, inflammation, psychiatric diseases, psychosis, oncology, encephalitis, malaria, allergy, immunological disorders, arthritis, gastrointestinal disorders, psychiatric disorders rheumatoid arthritis, psychosis or allergy, which method comprises administering an effective amount of a compound of claim 2 , or a pharmaceutically acceptable salt thereof, to a patient in need thereof.

Assignees

• Hoffmann La Roche

Inventors

• Frei Beat
• Gobbi Luca
• Grether Uwe
• Ricklin Fabienne
• Roever Stephan
• Rogers-Evans Mark
• Rombach Didier

Classifications

• C07D491/107 Primary

  with only one oxygen atom as ring hetero atom in the oxygen-containing ring · CPC title

• C07D413/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• A61K9/4858

  Organic compounds · CPC title

• A61K9/485

  Inorganic compounds · CPC title

• C07D401/12

  linked by a chain containing hetero atoms as chain links · CPC title