1,2,4-triazine-6-carboxamide kinase inhibitors

A compound of Formula (Ib) or a tautomer or a pharmaceutically acceptable salt thereof

• wherein
• HET is monocyclic heteroaryl comprising 1-4 heteroatoms selected from S, O and N, optionally substituted with 1 to 3 R1;
• and
• B1 is selected from the group consisting of CO—NRaRb, phenyl, monocyclic or bicyclic heteroaryl comprising 1-4 heteroatoms selected from S, O and N, and 3-8 membered heterocyclyl comprising 1-4 heteroatoms selected from S, O and N, wherein phenyl, heteroaryl, and heterocyclyl are each optionally substituted with 1 to 3 R2, and Ra and Rb together form a four to six membered heterocyclic ring optionally substituted with one to three groups independently selected from halo, C1-8alkyl, and haloC1-8alkyl;
• and wherein
• each R1 is independently selected from the group consisting of halo, C1-8alkyl, C2-8alkenyl, haloC1-8alkyl, (CH2)nSR1a, (CH2)nOR1a, O(CH2)jOR1a, (CH2)nNR1bR1c, (CH2)nCOR1e, (CH2)nCONR1bR1c, (CH2)nNR1bCOR1e, (CH2)nCONR1b(OR1a), (CH2)nCO2R1a, O(CH2)nCO2R1a, (CH2)nNR1bCO2R1a, (CH2)nSO2NR1bR1c, (CH2)nNR1bSO2R1e, (CH2)nSOR1e, (CH2)nSO2R1e, oxo, (CH2)nCN, N3, NO2, and -L-W, where n is 0, 1, 2, 3, 4, 5, or 6 and j is 1, 2, 3, 4, 5, or 6;
• L is selected from the group consisting of
• —O(CH2)b—, —SO—, —SO2—, —CO—, —NR1d—, —CONR1d(CH2)b—, —NR1dCO—, —NR1dSO2—, —SO2NR1d—, a bond, and —(CH2)z— where b is 0, 1, 2, 3, 4, or 5 and z is 1, 2, 3, 4, or 5;
• W is selected from the group consisting of aryl, monocyclic or bicyclic heteroaryl comprising 1-4 heteroatoms selected from S, O and N, C3-8cycloalkyl, and 3-8 membered heterocyclyl comprising 1-4 heteroatoms selected from S, O and N, each optionally substituted with 1 to 3 R2;
• each R2 is independently selected from the group consisting of halo, C1-8alkyl, C2-8alkenyl, haloC1-8alkyl, (CH2)mSR2a, (CH2)mOR2a, O(CH2)kOR2a, (CH2)mNR2bR2c, (CH2)mCOR2e, (CH2)mCONR2bR2c, (CH2)mNR2bCOR2e, (CH2)mCONR2b(OR2a), (CH2)mCO2R2a, O(CH2)mCO2R2a, (CH2)mNR2bCO2R2a, (CH2)mSO2NR2bR2c, (CH2)mNR2bSO2R2e, (CH2)mSOR2e, (CH2)mSO2R2e, oxo, (CH2)mCN, N3, and NO2, where m is 0, 1, 2, 3, 4, 5, or 6 and k is 1, 2, 3, 4, 5, or 6;
• R1a, R1b, R1c, R1d, R2a, R2b, and R2c are independently selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, and haloC1-8alkyl;
• R1e and R2e are independently selected from the group consisting of C1-8alkyl, C2-8alkenyl, and haloC1-8alkyl;
• Y is (CH2)v(X2), wherein
• v is 0, 1, 2, or 3;
• X2 is selected from the group consisting of CH2CH3, (CH2)3NH2, C3-8cycloalkyl, 3-8 membered heterocyclyl comprising 1-4 heteroatoms selected from S, O and N, aryl, and monocyclic or bicyclic heteroaryl comprising 1-4 heteroatoms selected from S, 0 and N, wherein cycloalkyl, heterocyclyl, aryl, and heteroaryl are each optionally substituted with 1 to 3 R10;
• R10 is independently selected from the group consisting of halo, C1-8alkyl, C2-8alkenyl, haloC1-8alkyl, (CH2)qSR10a, (CH2)qOR10a, (CH2)qNR10bR10c, (CH2)qCOR10d, (CH2)qCONR10bR10c, (CH2)qNR10bCOR10d, (CH2)qCONR10b(OR10a), (CH2)qCO2R10a, O(CH2)qCO2R10a, (CH2)qNR10bCO2R10a, (CH2)qSO2NR10bR10c, (CH2)qNR10bSO2R10d, (CH2)qSOR10d, (CH2)qSO2R10d, oxo, (CH2)qCN, N3, N═CH2, NO2, C(O)3-8 membered heterocyclyl comprising 1-4 heteroatoms selected from S, O and N, aryl, monocyclic or bicyclic heteroaryl comprising 1-4 heteroatoms selected from S, O and N, C3-8cycloalkyl, and 3-8 membered heterocyclyl comprising 1-4 heteroatoms selected from S, O and N, where aryl, cycloalkyl, heteroaryl, and heterocyclyl are each optionally substituted with 1 to 3 R11d and q is 0, 1, 2, 3, 4, 5, or 6;
• R11d is selected from the group consisting of halo, C1-8alkyl, haloC1-8alkyl, OH, C1-8alkoxy, haloC1-8alkoxy, C(O)C1-8alkyl, CO2C1-8alkyl, and SO2C1-8alkyl;
• R10a, R10b, and R10c are independently selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, and haloC1-8alkyl;
• and
• R10d is selected from the group consisting of C1-8alkyl, C2-8alkenyl, and haloC1-8alkyl.

A compound or a tautomer or a pharmaceutically acceptable salt thereof having a structure selected from

• 3-(((1R,2S)-2-aminocyclohexyl)amino)-5-((5-fluoropyridin-3-yl)amino)-1,2,4-triazine-6-carboxamide,
• 3-(((1R,2S)-2-aminocyclohexyl)amino)-5-((6-(dimethylcarbamoyl)pyridin-3-yl)amino)-1,2,4-triazine-6-carboxamide,
• 3-(((1R,2S)-2-aminocyclohexyl)amino)-5-((6-(azetidine-1-carbonyl)pyridin-3-yl)amino)-1,2,4-triazine-6-carboxamide,
• 3-(((1R,2S)-2-aminocyclohexyl)amino)-5-((6-fluoropyridin-3-yl)amino)-1,2,4-triazine-6-carboxamide,
• 3-(((1R,2S)-2-aminocyclohexyl)amino)-5-((2-methoxypyridin-4-yl)amino)-1,2,4-triazine-6-carboxamide,
• 3-(((1R,2S)-2-aminocyclohexyl)amino)-5-((1-methyl-1H-pyrazol-4-yl)amino)-1,2,4-triazine-6-carboxamide,
• 3-(((3R,4R)-3-aminotetrahydro-2H-pyran-4-yl)amino)-5-((1-methyl-1H-pyrazol-4-yl)amino)-1,2,4-triazine-6-carboxamide,
• 3-(((1R,2S)-2-aminocyclohexyl)amino)-5-(pyridin-3-ylamino)-1,2,4-triazine-6-carboxamide,
• 3-(((1R,2S)-2-aminocyclohexyl)amino)-5-((3-methylisothiazol-5-yl)amino)-1,2,4-triazine-6-carboxamide,
• 3-(((1R,2S)-2-aminocyclohexyl)amino)-5-((5-(4-fluorophenyl)isoxazol-3-yl)amino)-1,2,4-triazine-6-carboxamide,
• 3-(((1R,2S)-2-aminocyclohexyl)amino)-5-(thiazol-5-ylamino)-1,2,4-triazine-6-carboxamide,
• 3-(((1R,2S)-2-aminocyclohexyl)amino)-5-((3-phenyl-1,2,4-oxadiazol-5-yl)amino)-1,2,4-triazine-6-carboxamide,
• 3-(((3R,4R)-3-aminotetrahydro-2H-pyran-4-yl)amino)-5-((3-methylisothiazol-5-yl)amino)-1,2,4-triazine-6-carboxamide,
• 3-(((1R,2S)-2-aminocyclohexyl)amino)-5-(thiazol-5-ylamino)-1,2,4-triazine-6-carboxamide.