TRPV4 antagonists

A compound according to Formula I:

• wherein:
• R1 is selected from:
• aryl,
• aryl substituted from 1 to 4 times by Ra,
• heteroaryl,
• heteroaryl substituted from 1 to 4 times by Ra,
• bicycloheteroaryl, and
• bicycloheteroaryl substituted from 1 to 4 times by Ra;
• R2 is selected from:
• aryl,
• aryl substituted from 1 to 4 times by Rb,
• heteroaryl,
• heteroaryl substituted from 1 to 4 times by Rb,
• bicycloheteroaryl, and
• bicycloheteroaryl substituted from 1 to 4 times by Rb, and
• Y1 is selected from:
• C1-6alkyl, and
• C1-6alkyl substituted with from:
• 1 to 9 substitutents independently selected from:
• fluoro,
• chloro,
• bromo,
• iodo,
• —OC1-6alkyl,
• —OC1-6alkyl substituted with from 1 to 6 substituents independently selected from:
• fluoro, oxo, —OH, —COOH, —NH2, and —CN,
• mercapto,
• —S(O)H,
• —S(O)2H,
• oxo,
• hydroxy,
• amino,
• —NHRx11,
• where Rx11 is selected from C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from:
• fluoro, oxo, —OH, —COOH, —NH2, —CN, —OC1-5alkyl, —OC1-5alkyl substituted from 1 to 6 times by fluoro and —NH2,
• —NRx12Rx13,
• where Rx12 and Rx13 are each independently selected from C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from:
• fluoro, oxo, —OH, —COOH, —NH2, and —CN,
• —C(O)OH,
• —C(O)NH2,
• aryl,
• —Oaryl,
• heteroaryl,
• —Oheteroaryl,
• —S(O)2NH2,
• —NHS(O)2H,
• nitro, and
• cyano, or
• Y1 is taken together with the adjacent —OH to form a heterocyclic ring selected from:
• morpholinyl,
• morpholinyl substituted by —CH3, and
• oxazolidin-2-one;
• each Ra is independently selected from:
• fluoro,
• chloro,
• bromo,
• iodo,
• —OH,
• C1-6alkyl,
• C1-6alkyl substituted with from 1 to 5 substituents independently selected from:
• fluoro, chloro, bromo, iodo, C1-6alkyloxy, —OH, C1-4alkyl, phenyl, oxo, —COOH, —NO2, —NH2 and —CN,
• cyano,
• —OC1-6alkyl,
• —OC1-6alkyl substituted with from 1 to 5 substituents independently selected from:
• fluoro, chloro, bromo, iodo, C1-6alkyloxy, —OH, C1-6alkyl, phenyl, oxo, —COOH, —NO2, —NH2 and —CN,
• —Ophenyl,
• —C(O)OC1-6alkyl,
• —C(O)OC1-6alkyl substituted 1 to 5 times by fluoro, and
• —Ocycloalkyl;
• and
• each Rb is independently selected from:
• fluoro,
• chloro,
• bromo,
• iodo,
• —OH,
• C1-6alkyl,
• C1-6alkyl substituted with from 1 to 5 substituents independently selected from:
• fluoro, chloro, bromo, iodo, C1-6alkyloxy, —OH, C1-4alkyl, phenyl, oxo, —COOH, —NO2, —NH2 and —CN,
• cyano,
• —OC1-6alkyl,
• —OC1-6alkyl substituted with from 1 to 5 substituents independently selected from:
• fluoro, chloro, bromo, iodo, C1-6alkyloxy, —OH, C1-4alkyl, phenyl, oxo, —COOH, —NO2, —NH2 and —CN,
• phenyl,
• —C≡C—Si(CH3)3, and
• —C≡C-cycloalkyl;
• or a pharmaceutically acceptable salt thereof.