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1. (WO2015054103) OXAZOLIDINONES AS MODULATORS OF MGLUR5
Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

CLAIMS

We claim:

1. A compound of formula I


(I)

where:

R1 is hydrogen or alkyl;

R2 is hydrogen or alkyl;


R4 is cyano, alkyl, haloalkyl, cycloalkyl, hydroxy, alkoxy, haloalkoxy, or thioalkyl, where alkyl, haloalkyl, and cycloalkyl are substituted with 0-3 substituents selected from halo, alkyl, haloalkyl, hydroxy, and alkoxy;

or R4 is a bridged [l-4.1-4.0-3]bicycloalkyl;

or R4 is alkylcarbonylamino, haloalkylcarbonylamino, cycloalkanonyl,

valerolactamyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl,

tetrahydropyranyloxy, phenyl, or phenoxy;

or R4 is amino, alkylamino, dialkylamino, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, homopiperidinyl, homopiperazinyl, or homomorpholinyl; or R4 is pyrazolyl, isoxazolyl, isothiazolyl, imidazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, or indazolyl, and is substituted with 0-2 substituents selected from halo and alkyl;

L is a bond, alkylene, or hydroxyalkylene;

Ar1 is phenyl, pyridinyl, pyrazinyl, pyrimidinyl, or pyridazinyl, and is substituted with 1 R3 substituent and with 0-3 substituents selected from cyano, halo, alkyl, haloalkyl, alkoxy, and haloalkoxy; and

Ar2 is phenyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, furanyl, thienyl, pyrazolyl, isoxazolyl, isothiazolyl, imidazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, or benzimidazolyl, and is substituted with 0-3 substituents selected from cyano, halo, alkyl, haloalkyl, hydroxy, alkoxy, haloalkoxy, and phenyl;

or a pharmaceuticallyacceptable salt thereof.

2. A compound of claim 1 where

R1 is hydrogen;

R2 is hydrogen;


R4 is cyano, alkyl, haloalkyl, cycloalkyl, hydroxy, alkoxy, haloalkoxy, or thioalkyl, where alkyl, haloalkyl, and cycloalkyl are substituted with 0-3 substituents selected from halo, alkyl, haloalkyl, hydroxy, and alkoxy;

or R4 is a bridged [l-4.1-4.0-3]bicycloalkyl;

or R4 is alkylcarbonylamino, haloalkylcarbonylamino, cycloalkanonyl,

valerolactamyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl,

tetrahydropyranyloxy, phenyl, or phenoxy;

or R4 is amino, alkylamino, dialkylamino, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, homopiperidinyl, homopiperazinyl, or homomorpholinyl;

or R4 is pyrazolyl, isoxazolyl, isothiazolyl, imidazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, or indazolyl, and is substituted with 0-2 substituents selected from halo and alkyl;

L is a bond, alkylene, or hydroxyalkylene;

Ar1 is phenyl, pyridinyl, pyrazinyl, pyrimidinyl, or pyridazinyl, and is substituted with 1 R3 substituent and with 0-3 substituents selected from cyano, halo, alkyl, haloalkyl, alkoxy, and haloalkoxy; and

Ar2 is phenyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, furanyl, thienyl, pyrazolyl, isoxazolyl, isothiazolyl, imidazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, or benzimidazolyl, and is substituted with 0-3 substituents selected from cyano, halo, alkyl, haloalkyl, hydroxy, alkoxy, haloalkoxy, and phenyl;

or a pharmaceuticallyacceptable salt thereof.

pound of claim 2 where R1 is hydrogen; R2 is hydrogen; R3 is


; R is cyano, alkyl, haloalkyl, cycloalkyl, hydroxy, alkoxy, haloalkoxy, or thioalkyl, where alkyl, haloalkyl, and cycloalkyl are substituted with 0-3 substituents selected from halo, alkyl, haloalkyl, hydroxy, and alkoxy; or R4 is a bridged [l-4.1-4.0-3]bicycloalkyl; or R4 is alkylcarbonylamino,

haloalkylcarbonylamino, cycloalkanonyl, valerolactamyl, oxetanyl,

tetrahydrofuranyl, tetrahydropyranyl, tetrahydropyranyloxy, phenyl, or phenoxy; or R4 is amino, alkylamino, dialkylamino, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, homopiperidinyl, homopiperazinyl, or homomorpholinyl; or R4 is pyrazolyl, isoxazolyl, isothiazolyl, imidazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, or indazolyl, and is substituted with 0-2 substituents selected from halo and alkyl; L is a bond, alkylene, or hydroxyalkylene; Ar1 is pyridinyl substituted with 1 R3 substituent and with 0-3 substituents selected from cyano, halo, alkyl, haloalkyl, alkoxy, and haloalkoxy; and Ar2 is phenyl substituted with 0-3 substituents selected from cyano, halo, alkyl, haloalkyl, hydroxy, alkoxy, haloalkoxy, and phenyl; or a pharmaceuticallyacceptable salt thereof.

4. A compound of claim 1 where R1 and R2 are hydrogen.

5. A compound of claim 1 where R4 is cyano, alkyl, haloalkyl, cycloalkyl, hydroxy, alkoxy, haloalkoxy, or thioalkyl, where alkyl, haloalkyl, and cycloalkyl are substituted with 0-3 substituents selected from halo, alkyl, haloalkyl, hydroxy, and alkoxy.

6. A compound of claim 1 where R4 is amino, alkylamino, dialkylamino, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, homopiperidinyl, homopiperazinyl, or homomorpholinyl.

7. A compound of claim 1 where R4 is pyrazolyl, isoxazolyl, isothiazolyl, imidazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, or indazolyl, and is substituted with 0-2 substituents selected from halo and alkyl.

8. A compound of claim 1 where L is a bond, methylene, or hydroxymethylene.

9. A compound of claim 1 where Ar1 is pyridinyl substituted with 1 R3 substituent and with 0-3 substituents selected from cyano, halo, alkyl, haloalkyl, alkoxy, and haloalkoxy.

10. A compound of claim 1 where Ar2 is phenyl substituted with 0-3 substituents selected from cyano, halo, alkyl, haloalkyl, hydroxy, alkoxy, haloalkoxy, and phenyl.

11. A compound of claim 1 with the indicated stereochemistry


12. A composition comprising a compound of claim 1, or a

pharmaceuticallyacceptable salt thereof, and a pharmaceutically acceptable carrier.

13. A method for the treatment of schizophrenia, Alzheimer's disease, cognitive impairment, Parkinson's disease, Parkinson's disease levodopa-induced dyskinesia, addiction, anxiety, depression, psychosis, epilepsy, Fragile X, gastroesophageal reflux disease, migraine, pain, borderline personality disorder, bipolar disorder, or other neurological or psychiatric disorders associated with glutamate dysfunction, which comprises administering to a patient a therapeutically affective amount of a compound of claim 1.

14. The method of claim 13 directed to schizophrenia.

15. The method of claim 13 directed to Alzheimer's Disease.