IP Library › Granted Patent US 10,308,659
Granted Patent B2
US 10,308,659 · App. 14/868,305 · Granted Jun 4, 2019

Pyridine derivatives

Inventors: Olivier Gavelle (Hagenthal-le-Bas, FR); Uwe Grether (Efringen-Kirchen, DE); Atsushi Kimbara (Shizuoka, JP); Matthias Nettekoven (Grenzach-Wyhlen, DE); Roever Stephan (Inzlingen, DE); Mark Rogers-Evans (Bottmingen, CH); Didier Rombach (Mulhouse, FR); Tanja Schulz-Gasch (Ziefen, CH)
Assignee: HOFFMANN-LA ROCHE INC.
C07D491/107C07D401/04C07D401/14C07D403/04C07D413/04C07D413/14
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Quick Facts
Patent No.
US 10,308,659
App. No.
14/868,305
Granted
Jun 4, 2019
Kind
B2
Abstract

The invention relates to a compound of formula (I) wherein A and 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.

Claims (106)

1. A compound selected from the group consisting of:

5-[5-cyclopropyl-4-(cyclopropylmethoxy)pyridin-2-yl]-3-methyl-1,2,4-oxadiazole;

5[5-cyclopropyl-4-(cyclopropylmethoxy)pyridin-2-yl]-3-phenyl-1,2,4-oxadiazole;

3-cyclopropyl-5-[5-cyclopropyl-4-(cyclopropylmethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

3-cyclopentyl-5-[5-cyclopropyl-4-(cyclopropylmethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

3-benzyl-5-[5-cyclopropyl-4-(cyclopropylmethoxy)pyridin-2-yl]1,2,4-oxadiazole;

3-tert-butyl-5-[5-cyclopropyl-4-(cyclopropylmethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

3-cyclopropyl-5-[5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-[5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-3-(trifluoromethyl)-1,2,4-oxadiazole;

5-cyclopropyl-3-[5-cyclopropyl-4-(cyclopropylmethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(cyclopropylmethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

3-[5-cyclopropyl-4-(cyclopropylmethoxy)pyridin-2-yl]-5-(methoxymethyl)-1,2,4-oxadiazole;

3-[5-cyclopropyl-4-(cyclopropylmethoxy)pyridin-2-yl]-5-ethyl-1,2,4-oxadiazole;

3-[5-cyclopropyl-4-(cyclopropylmethoxy)pyridin-2-yl]-5-propan-2-yl-1,2,4-oxadiazole;

[3-[5-cyclopropyl-4-(cyclopropylmethoxy)pyridin-2-yl]-1,2,4-oxadiazol-5-yl]methanol;

3-[5-cyclopropyl-4-(cyclopropylmethoxy)pyridin-2-yl]-5-(trifluoromethyl)-1,2,4-oxadiazole;

1-[3-[5-cyclopropyl-4-(cyclopropylmethoxy)pyridin-2-yl]-1,2,4-oxadiazol-5-yl]cyclopropan-1-ol;

3-[5-cyclopropyl-4-(cyclopropylmethoxy)pyridin-2-yl]-5-(1-methylcyclopropyl)-1,2,4-oxadiazole;

1-[3-[5-cyclopropyl-4-(cyclopropylmethoxy)pyridin-2-yl]-1,2,4-oxadiazol-5-yl]cyclopropane-1-carboxamide;

2-[3-[5-cyclopropyl-4-(cyclopropylmethoxy)pyridin-2-yl]-1,2,4-oxadiazol-5-yl]propan-2-ol;

5-tert-butyl-3-[5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

3-[5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-5-(1-methylcyclopropyl)-1,2,4-oxadiazole;

3-[5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-5-propan-2-yl-1,2,4-oxadiazole;

1-[3-[5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-1,2,4-oxadiazol-5-yl]cyclopropan-1-ol;

3-[5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

3-tert-butyl-5-[5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-[5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-3 -propan-2-yl-1,2,4-oxadiazole;

5-tert-butyl-3-[4-(cyclopropylmethoxy)-5-methylsulfonylpyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-[(2S)-1,1,1-trifluoropropan-2-yl]oxypyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-[(2R)-1,1,1-trifluoropropan-2-yl]oxypyridin-2-yl]-1,2,4-oxadiazole;

3-tert-butyl-5-[5-cyclopropyl-4-[(2R)-1,1,1-trifluoropropan-2-yl]oxypyridin-2-yl]-1,2,4-oxadiazole;

3-tert-butyl-5-[5-cyclopropyl-4-[(2S)-1,1,1-trifluoropropan-2-yl]oxypyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3[5-cyclopropyl-4-[(4-fluorophenyl)methoxy]pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-[(3-methyloxetan-3-yl)methoxy]pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(oxolan-2-ylmethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]pyridin -2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(oxetan-2-ylmethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(4-fluorophenoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-methylsulfonyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-chloro-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

3-[5-chloro-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-5-cyclopropyl-1,2,4-oxadiazole;

5-cyclopropyl-3-[5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(4-methylsulfonylphenoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-(5-cyclopropyl-4-cyclopropylsulfonylpyridin-2-yl)-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(2-ethoxyethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(1-methoxybutan-2-yloxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3[5-cyclopropyl-4-[2-[(2-methylpropan-2-yl)oxy]ethoxy]pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-[1-[(2-methylpropan-2-yl)oxy]propan-2-yloxy]pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5cyclopropyl-4-(1-methoxypropan-2-yloxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(3-methoxybutoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(oxetan-3-ylmethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-cyclopropyl-3-[5-cyclopropyl-4-[(2S)-1,1,1-trifluoropropan-2-yl]oxypyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(2-pyrrolidin-l-ylethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(2-piperidin-l-ylethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(1-piperidin-1-ylpropan-2-yloxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-[(1-methylpiperidin-2-yl)methoxy]pyridin-2-yl]-1,2,4-oxadiazole;

2-[2-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-5-cyclopropylpyridin-4-yl]oxy-N,N-diethylpropan-1-amine;

3-[[2-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-5-cyclopropylpyridin-4-yl]oxyethyl]morpholine;

4-[2-[2-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-5-cyclopropylpyridin-4-yl]oxyethyl]morpholine;

5-tert-butyl-3-[5-cyclopropyl-4-[(3-fluorooxetan-3-yl)methoxy]pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-[(2,5-dimethyl-1,3-oxazol-4-yl)methoxy]pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-[(5-methyl-1,2-oxazol-3-yl)methoxy]pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(3-methylsulfonylphenoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-(6-chloro-5-cyclopropyl-4-(4-fluorobenzyloxy)pyridin-2-yl)-1,2,4-oxadiazole;

2-tert-butyl-5-[5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-1,3,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(2,2-difluoroethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(2-fluoroethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(pyridin-2-ylmethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-[(5-fluoropyridin-2-yl)methoxy]pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(pyridin-3-ylmethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

2-tert-butyl-5-[5-cyclopropyl-4-[(2S)-1,1,1-trifluoropropan-2-yl]oxypyridin-2-yl]-1,3,4-oxadiazole;

3-tert-butyl-5-[5-cyclopropyl-4-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]pyridin-2-yl]-1,2,4-oxadiazole; and

3-tert-butyl-5-(5-cyclopropyl-4-(2,2-difluoroethoxy)pyridin-2-yl)-1,2,4-oxadiazole;

or a pharmaceutically acceptable salt thereof.

2. A compound selected from the group consisting of:

5-tert-butyl-3-[5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

3 -tert-butyl-5-[5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-[(3-methyloxetan-3-yl)methoxy]pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(oxolan-2-ylmethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(4-fluorophenoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(2-ethoxyethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(3-methoxybutoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(oxetan-3-ylmethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-[(5-fluoropyridin-2-yl)methoxy]pyridin-2-yl]-1,2,4-oxadiazole;

3-tert-butyl-5-(5-cyclopropyl-4-(2,2-difluoroethoxy)pyridin-2-yl)-1,2,4-oxadiazole;

or a pharmaceutically acceptable salt thereof.

3. A compound of claim 2 selected from the group consisting of:

5-tert-butyl-3-[5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-[(3-methyloxetan-3-yl)methoxy]pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(oxolan-2-ylmethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(4-fluorophenoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(2-ethoxyethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(3-methoxybutoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-(oxetan-3-ylmethoxy)pyridin-2-yl]-1,2,4-oxadiazole;

5-tert-butyl-3-[5-cyclopropyl-4-[(5-fluoropyridin-2-yl)methoxy]pyridin-2-yl]-1,2,4-oxadiazole;

or a pharmaceutically acceptable salt thereof.

4. A compound of claim 2 selected from the group consisting of:

3-tert-butyl-5-(5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl)-1,2,4-oxadiazole;

3-tert-butyl-5-(5-cyclopropyl-4-(2,2-difluoroethoxy)pyridin-2-yl)-1,2,4-oxadiazole;

or a pharmaceutically acceptable salt thereof.

5. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.

6. A pharmaceutical composition comprising a compound of claim 2 , or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.

7. A pharmaceutical composition comprising a compound of claim 3 , or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.

8. A pharmaceutical composition comprising a compound of claim 4 , or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.

9. A compound, which is 3-tert-butyl-5-[5-cyclopropyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]-1,2,4-oxadiazole, or a pharmaceutically acceptable salt thereof.

10. A pharmaceutical composition comprising a compound of claim 9 , or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 8, 2015
From: GAVELLE, OLIVIER; GRETHER, UWE; NETTEKOVEN, MATTHIAS; ROGERS-EVANS, MARK; ROMBACH, DIDIER; ROEVER, STEPHAN; SCHULZ-GASCH, TANJA
To: F. HOFFMANN-LA ROHCE AG
Reel/Frame 036760/0184 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 8, 2015
From: KIMBARA, ATSUSHI
To: F. HOFFMANN-LA ROHCE AG
Reel/Frame 036760/0438 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 8, 2015
From: F. HOFFMANN-LA ROHCE AG
To: HOFFMANN-LA ROCHE INC.
Reel/Frame 036760/0484 →
Priority Claims (1)
EP 13161176 · Mar 26, 2013 · regional
Continuity (2)
Continuation PCTEP2014055797 · Mar 24, 2014
Related Publication 20160016968A1 · Jan 21, 2016
Cited By (2)
US 12,617,768 US 12,709,605