Novel pyridine derivatives

Patent metadata

Field	Value
Publication number	US-2016137606-A1
Application number	US-201615002681-A
Country	US
Kind code	A1
Filing date	Jan 21, 2016
Priority date	Jun 10, 2011
Publication date	May 19, 2016
Grant date	—

Abstract

The invention relates to a compound of formula (I)

wherein R 1 to R 4 are defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.

First claim

1 . A compound of formula (I)

wherein
R 1 is selected from the group consisting of: cycloalkyl, cycloalkylalkoxy, haloalkoxy, alkoxyalkoxy, phenyl, halophenyl, haloalkylphenyl, phenylalkyl, halophenylalkyl, phenylhydroxyalkyl, phenyloxyalkyl, phenylalkoxy, alkoxyphenyl, halophenyloxy, piperidinylsulfonyl, tetrahydropyranyl, 3-alkoxy-azetidinyl, tetrahydropyranylalkyl, tetrahydropyranylalkoxy, tetrahydrothiopyranyl 1,1-dioxide, 1,1-dioxo-[1,2]thiazinan-4-yl, piperidin-2-onyl, tetrahydrofuranylalkoxy, pyridinylalkoxy, alkyloxetanylalkoxy, hydroxylhaloalkyloxy, halophenylhydroxyalkyl, alkylsulfonyl, alkylsulfanyl and (halo)(haloalkyl)phenyl;
R 2 is selected from the group consisting of: hydrogen, halogen, alkyl, haloalkyl, hydroxyalkyl, cycloalkyl, hydroxycycloalkyl, alkoxy, haloalkoxy, alkylamino, haloalkylamino, tetrahydropyranyl, 1H-pyrazolyl, pyrrolidinyl, alkylpyrrolidinyl, halopyrrolidinyl, oxopyrrolidinyl, haloazetidinyl, hydroxyazetidinyl, 1,1-dioxido-2-isothioazolidinyl, tetrahydrofuranyl, cycloalkylamino, hydroxyoxetanyl, alkylsulfonyl, oxetanyl, 6oxa-1-aza-spiro[3.3]heptyl, 3,3-difluoro-2-oxo-azetidinyl, oxo-azetidinyl and oxo-pyrrolidinyl;
or R 1 and R 2 together with the ring to which they are attached form tetrahydroquinolinyl or alkyltetrahydroquinolinyl;
one of R 3 and R 4 is hydrogen and the other one is —(CR 5 R 6 ) m (CR 7 R 8 ) n —R 9 ;
or R 3 and R 4 together with the nitrogen atom to which they are attached form piperidinyl, 1,1-dioxidotetrahydro-2H-thiopyranyl, thiomorpholinyl, 2-oxa-6-aza-spiro[3.3]heptyl or 1-hydroxyalkylpyrrolidinyl;
R 5 and R 6 are each independently selected from the group consisting of: hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, phenyl, pyridazinyl, halophenyl, pyrimidinyl, alkylsulfanylalkyl and alkylsulfonylalkyl;
or R 5 and R 6 together with the carbon atom to which they are attached form cycloalkyl, tetrahydropyranyl or oxetanyl;
R 7 and R 8 are each independently selected from the group consisting of: hydrogen, alkyl and cycloalkyl;
R 9 is selected from the group consisting of: alkyl, hydroxyl, cyano, carboxyl, alkoxycarbonyl, alkyl[1,2,4]oxadiazolyl, oxazolyl, thiazolyl, [1,3,4]oxadiazolyl, cycloalkyl, phenyl, pyridinyl, tetrahydropyranyl, alkyl[1,2,4]thiadiazolyl, [1,2,4]thiadiazolyl, alkylaminocarbonyl, alkyltetrahydropyranyl, alkylisoxazolyl, aminocarbonyl, morpholinyl, dihydro-oxazolyl, [1,2,4]oxadiazolyl, hydroxycycloalkyl, alkoxycarbonylcycloalkyl, alkoxyalkoxy, hydroxyalkylcycloalkyl, alkoxypyridinyl, piperidinyl, hydroxypiperidinyl, hydroxyalkylpiperidinyl, isoxazolyl, azetidine-carbonyl, alkoxyalkylaminocarbonyl, cycloalkyl-alkylaminocarbonyl, haloazetidinylcarbonyl, alkyloxopyrrolidinyl, 1,1-dioxo-tetrahydro-1λ6-thiophenyl, 1,1-dioxo-tetrahydro-1λ6-thiophenylamino, amino[1,2,4]oxadiazolyl, 4-alkyl-5-oxo-4,5-dihydro-[1,2,4]oxadiazolyl, nitro-benzo[1,2,5]oxadiazolyl, alkylsulfonyl, alkyl[1,2,4]thiazolyl, hydroxyalkylaminocarbonyl, oxotetrahydrofuranyl, (cycloalkylalkyl)(alkoxycarbonyl)amino, 2-oxo-[1,3]oxazinanyl, haloalkyl and hydroxypyrrolidinylaminocarbonyl;
m is 0 or 1; and
n is 0, 1 or 2;
or a pharmaceutically acceptable salt or ester thereof.

2 . A compound according to claim 1 , wherein R 1 is selected from the group consisting of: cycloalkyl, cycloalkylalkoxy, haloalkoxy, alkoxyalkoxy, phenyl, halophenyl, haloalkylphenyl, halophenylalkyl, halophenyloxy, piperidinylsulfonyl, tetrahydropyranyl, tetrahydropyranylalkoxy, tetrahydrofuranylalkoxy, pyridinylalkoxy, hydroxyhaloalkyloxy, halophenylhydroxyalkyl, alkylsulfanyl and alkylsulfonyl.

3 . A compound according to claim 1 , wherein R 1 is selected from the group consisting of: cycloalkyl, cycloalkylalkoxy, haloalkoxy, alkoxyalkoxy, hdophenyl, halophenylalkyl, alkoxyphenyl, halophenyloxy, piperidinylsulfonyl, tetrahydropyranyl, tetrahydropyranylalkoxy tetrahydrofuranylalkoxy, hydroxyhaloalkyloxy, halophenylhydroxyalkyl, alkylsulfanyl and alkylsulfonyl.

4 . A compound according to claim 1 , wherein R 1 is selected from the group consisting of: cycloalkylalkoxy, halophenyl, halophenylalkyl, tetrahydropyranylalkoxy, tetrahydrofuranylalkoxy, haloalkoxy, hydroxylhaloalkyloxy, halophenylhydroxyalkyl, alkylsulfanyl and alkylsulfonyl.

5 . A compound according to claim 1 , wherein R 1 is selected from the group consisting of: cyclopropylmethoxy, chlorophenyl, fluorophenylmethyl, fluorochlorophenyl, tetrahydropyranylmethoxy, tetrahydrofuranylmethoxy, pentafluoropopyloxy, trifluorohydroxybutyloxy, fluorophenylhydroxymethyl, butylsulfanyl and butylsulfonyl.

6 . A compound according to claim 1 , wherein R 2 is selected from the group consisting of: hydrogen, halogen, alkyl, haloalkyl, cycloalkyl, hydroxycycloalkyl, alkoxy haloalkylamino, tetrahydropyranyl, 1H-pyrazolyl, pyrrolidinyl, alkylpyrrolidinyl, halopyrrolidinyl, oxopyrrolidinyl, haloazetidinyl, hydroxyazetidinyl, 1,1-dioxido-2-isothioazolidinyl, tetrahydrofuranyl, cycloalkylamino, hydroxyoxetanyl and 6oxa-1-aza-spiro[3.3]heptyl.

7 . A compound according to claim 1 , wherein R 2 is selected from the group consisting of: hydrogen, alkyl, haloalkyl, cycloalkyl, haloalkylamino, tetrahydropyranyl, pyrrolidinyl, alkylpyrrolidinyl, halopyrrolidinyl, haloazetidinyl, tetrahydrofuranyl, cycloalkylamino and 6-oxa-1-aza-spiro[3.3]heptyl.

8 . A compound according to claim 1 , wherein R 2 is selected from the group consisting of: hydrogen, methyl, trifluoromethyl, cyclopropyl, cyclopentyl, bis(trifluoroethyl)amino, tetrahydropyranyl, pyrrolidinyl, methylpyrrolidinyl, difluoropyrrolidinyl, difluoroazetidinyl, tetrahydrofuranyl, cyclopropylamino and 6oxa-1-aza-spiro[3.3]heptyl.

9 . A compound according to claim 1 , wherein R 1 and R 2 together with the ring to which they are attached form dimethyltetrahydroquinolinyl.

10 . A compound according to claim 1 , wherein R 5 and R 6 are each independently selected from the group consisting of: hydrogen, methyl, ethyl, propyl, butyl, pentyl, trifluoromethyl, cyclopropyl, cyclopropylmethyl, phenyl, fluorophenyl and pyridazinyl or R 5 and R 6 together with the carbon atom to which they are attached form cyclobutyl, tetrahydropyranyl or cyclopropyl.

11 . A compound according to claim 1 , wherein R 7 and R 8 are each independently selected from hydrogen and methyl.

12 . A compound according to claim 1 , wherein R 9 is selected from the group consisting of: hydroxyl, cyano, carboxyl, alkoxycarbonyl, alkyl[1,2,4]oxadiazolyl, oxazolyl, thiazolyl, [1,3,4]oxadiazolyl, cycloalkyl, phenyl, pyridinyl, tetrahydropyranyl, alkyl[1,2,4]thiadiazolyl, alkylaminocarbonyl, alkyltetrahydropyranyl, alkylisoxazolyl, aminocarbonyl, morpholinyl, dihydro-oxazolyl, [1,2,4]oxadiazolyl, hydroxycycloalkyl, alkoxycarbonylcycloalkyl, alkoxyalkoxy, hydroxyalkylcycloalkyl, piperidinyl, haloazetidinylcarbonyl, nitro-benzo[1,2,5]oxadiazolyl and alkyl.

13 . A compound according to claim 1 , wherein R 9 is selected from the group consisting of: hydroxyl, carboxyl, alkyl[1,2,4]oxadiazolyl, thiazolyl, alkylaminocarbonyl, aminocarbonyl, morpholinyl, alkoxyalkoxy, piperidinyl, cyano, pyridinyl, haloazetidinylcarbonyl, nitro-benzo[1,2,5]oxadiazolyl, alkoxycarbonyl and alkyl.

14 . A compound according to claim 1 , wherein R 9 is selected from the group consisting of: hydroxyl, methyl[1,2,4]oxadiazolyl, thiazolyl, methylaminocarbonyl, aminocarbonyl, morpholinyl, methoxymethoxy, piperidinyl, cyano, pyridinyl, nitro benzo[1,2,5]oxadiazolyl, di

Assignees

• Hoffmann La Roche

Inventors

• Bissantz Caterina
• Grether Uwe
• Hebeisen Paul
• Kimbara Atsushi
• Liu Qingping
• Nettekoven Matthias
• Prunotto Marco
• Roever Stephan
• Rogers-Evans Mark
• Schulz-Gasch Tanja
• Ullmer Christoph
• Wang Zhiwei
• Yang Wulun

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title