Amide substituted thiazoles as modulators of RORyt

A compound of Formula I:

• wherein:
• is phenyl, pyridyl, pyrimidyl, pyrazinyl, or pyridazyl;
• R1 is Cl, —CN, H, F, OC(1-4)alkyl, OCHF2,
• OCF3, C(1-4)alkyl, Br, I, or cyclopropyl;
• wherein said C(1-4)alkyl is optionally substituted with up to six fluorine atoms;
• R2 is F, Cl, —CN, H, OC(1-4)alkyl, OCHF2, OCF3, cyclopropyl, or C(1-4)alkyl;
• wherein said C(1-4)alkyl is optionally substituted with up to five fluorine atoms, and said cyclopropyl is optionally substituted with OH, CH3, CF3, and up to five fluorine atoms;
• or R1 and R2 may be taken together with their attached ring A to form a fused ring system selected from the group consisting of naphthalenyl, tetrahydronaphthalenyl, isoquinolinyl, quinolinyl, 2,3-dihydro-1H-indenyl, chromanyl, isochromanyl, and naphthyridinyl;
• wherein said naphthalenyl, tetrahydronaphthalenyl, isoquinolinyl, quinolinyl, 2,3-dihydro-1H-indenyl, chromanyl, isochromanyl, and naphthyridinyl may optionally be substituted with up to three substituents independently selected from the group consisting of F, OC(1-3)alkyl or C(1-3)alkyl wherein said OC(1-3)alkyl and C(1-3) alkyl is optionally substituted with up to five fluorine atoms (including CHF2, CH2F, CF3, and CH3;
• provided that R2 may not be H if R1 is H;
• R3 is thiadiazolyl, oxadiazolyl, isoxadiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, 1,2,4-oxadiazol-5(4H)-on-3-yl, pyridyl, thiazolyl, pyrimidyl, pyridazyl, pyrazyl, imidazolyl, pyrrolyl, furanyl, or phenyl;
• wherein said thiadiazolyl, oxadiazolyl, isoxadiazolyl, oxazolyl, isoxazolyl, triazolyl, pyridyl, thiazolyl, pyrimidyl, pyridazyl, pyrazyl, imidazolyl, pyrrolyl, furanyl, or phenyl is optionally substituted with R4, and further optionally substituted with one substituent selected from the group consisting of F, CH3, CF3, and cyclopropyl;
• R4 is H, C(1-6)alkylSO2C(1-6)alkyl, C(O)NH2, C(1-6)alkyl, CN, C(3-6)cycloalkyl, NH2, NH(C(1-6)alkyl), N(C(1-6)alkyl)2, NHCO(C(1-6)alkyl), N(C(1-6)alkyl)CO(C(1-6)alkyl), NHSO2(C(1-6)alkyl), N(C(1-6)alkyl)SO2(C(1-6)alkyl), O(C(1-6)alkyl), C(O)NH2, CONH(C(1-6)alkyl), CON(C(1-6)alkyl)2, SO2NH2, SO2NH(C(1-6)alkyl), SO2NH(COC(1-6)alkyl), or SO2N(C(1-6)alkyl)2;
• wherein said C(1-6)alkyl or C(3-6)cycloalkyl is optionally substituted independently with up to six fluorine atoms, CF3, CO2H, OH, —CN, C(O)NH2, NH2, OCH3, OCHF2, OCF3, —(CX2)m—, or N(CH3)2;
• m is 2, 3, 4, or 5;
• X is H, or F;
• wherein each occurance of X in a single molecule is independently defined;
• A1 is H, or C(1-4)alkyl;
• wherein said C(1-4)alkyl is optionally substituted with up to six fluorine atoms, Cl, —CN, OCH3, OCHF2, or OCF3;
• A2 is C(1-6)alkyl, C(0-2)alkyl-C(3-6)cycloalkyl,
• CH2—C6H4—C(O)NH2, —C6H4—F, CH2—CCH, or CH2—CC—CH3;
• wherein said C(1-6)alkyl, and said C(0-2)alkyl-C(3-6)cycloalkyl are optionally substituted with up to six fluorine atoms, Cl, —CN, OCH3, OCHF2, or OCF3;
• or A1 and A2 may be taken together with their attached nitrogen to form a ring selected from the group consisting of:
• thiomorpholinyl, piperidinyl, pyrrolidinyl, piperazinyl, morpholinyl, azetidinyl, and aziridinyl;
• wherein said piperidinyl, pyrrolidinyl, piperazinyl, morpholinyl, azetidinyl, and aziridinyl are optionally substituted with CF3, CH2CH2F, C(1-2)cycloalkyl, —CN, OH, CH2OH, CH2F, F, Cl, OCH3, OCHF2, OCF3, —(CX2)nO(CX2)n—, or —(CX2)n—, and up to three additional substituents selected from the group consisting of CH3 and F;
• n is independently 0, 1, 2, 3, or 4;
• X is H, or F;
• wherein each occurrence of X in a single molecule is independently defined;
• R5 is SO2NA3A4, CONA3A4, NA3A4, OCH2C(CF3)2OH, C(3-6)cycloalkyl, or C(1-6)alkyl;
• wherein said C(3-6)cycloalkyl and said C(1-6)alkyl are optionally substituted with OH, Cl, —CN, H, OCH3, OCHF2, OCF3, or NA3A4, further optionally substituted with —CH2CH2— attached to the same carbon atom, and up to seven fluorine atoms;
• A3 is H, or C(1-4)alkyl;
• wherein said C(1-4)alkyl is optionally substituted with OH, Cl, —CN, OCH3, OCHF2, or OCF3;
• and up to six fluorine atoms;
• A4 is H, C(1-6)alkyl, C(3-6)cycloalkyl, or C(3-6)heterocycloalkyl;
• wherein said C(1-6)alkyl is optionally substituted with cyclopropyl, morpholinyl, OH, OCH3, C(O)NH2, Cl, —CN, OCHF2, OCF3 and additionally substituted with up to three fluorine atoms;
• and wherein said C(3-6)cycloalkyl, and C(3-6)heterocycloalkyl are optionally substituted with CF3, CH3, —CN, C(O)NH2, and up to three fluorine atoms;
• or A3 and A4 can be taken together with their attached nitrogen to form a ring selected from the group consisting of piperidinyl, morpholinyl, piperazinyl, pyrrolidinyl, aziridinyl, and azetidinyl wherein said piperidinyl, morpholinyl, piperazinyl, pyrrolidinyl, aziridinyl, and azetidinyl are optionally substituted with up to four groups selected from the group consisting of CF3, OH, CH3, CH2F, and CHF2;
• and further optionally substituted with up to four groups selected from the group consisting of CF3, OH, CH3, CH2F, and CHF2;
• and further optionally substituted with up to six fluorine atoms;
• and pharmaceutically acceptable salts thereof.