Diaminopyrimidines and uses thereof

摘要

This disclosure relates to: (a) compounds and salts thereof that, inter alia, inhibit RSV infection and/or replication; (b) intermediates useful for the preparation of such compounds and salts; (c) compositions comprising such compounds and salts; (d) methods for preparing such intermediates, compounds, salts, and compositions; (e) methods of use of such compounds, salts, and compositions; and (f) kits comprising such compounds, salts, and compositions.;

主权项

1. A compound having formula (I), or a pharmaceutically acceptable salt thereof,wherein:
R1 is cyclohexyl optionally substituted with 1, 2, 3, or 4 substituents selected from the group consisting of C1-C10-alkyl, C2-C10-alkenyl, C2-C10-alkynyl, C1-C10-haloalkyl, C2-C10-haloalkenyl, C2-C10-haloalkynyl, halogen, oxo, cyano, hydroxy, —O—C1-C6-alkyl, O—C1-C6-haloalkyl, —C1-C3-alkylene-O—H, C1-C3-alkylene-O—C1-C6-alkyl, —C1-C3-alkylene-O—C1-C6-haloalkyl, —C1-C3-alkylene-NH2, —NH2, —C(O)O—C1-C6-alkyl, —N(Rb1)C(O)Rb1, —CON(Ra1)(Rb1), —C(O)Rb1, —OC(O)Rb1, —OS(O)2N(Ra1)(Rb1), —CO2H, —CO2Rb1, —N(Rb1)C(O)N(Rb1)2, —S—Rb1, —S(O)2Rb1, —S(O)Rb1, —SO2N(Ra1)(Rb1), —N(Ra1)(Ra1), —N(Rb1)S(O)2Rb1, —N(Rb1)C(O)O(Rb1), —N(Rb1)S(O)2O(Rb1), -L1a-O—Rb1, -L1a-CN, -L1a-N(Rb1)C(O)Rb1, -L1a-CON(Ra1)(R1b), -L1a-C(O)Rb1, L1a-OC(O)Rb1, -L1a-CO2H, -L1a-CO2Rb1, -L1a-N(Rb1)C(O)N(Rb1)2, L1a-S—Rb1, -L1a-S(O)2Rb1, -L1a-S(O)Rb1, -L1a-SO2—N(Ra1)Rb1), -L1a-(Ra1)(Rb1), -L1a-N(Rb1)S(O)2Rb1, and -L1a-N(Rb1)C(O)O(Rb1); R2 is methyl or ethyl; R3 is methyl or ethyl; R4 and R5 are independently selected from the group consisting of hydrogen, C1-C6-alkyl, and C1-C6-haloalkyl; R6 is selected from the group consisting of hydrogen, C1-C6-alkyl, and C1-C6-haloalkyl; G1 is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halogen, C1-C6-alkyl, C1-C6-haloalkyl, —O—Rf, —CN, —N(Rf)C(O)Rf, —CON(Re)(Rf), —C(O)Rf, —OC(O)Rf, —CO2H, —CO2Rf, —N(Rf)C(O)N(Rf)2, —S—Rf, —S(O)2Rf, —S(O)Rf, —SO2N(Re)(Rf), —N(Re)(Rf), —N(Rf)S(O)2Rf, —N(Rf)C(O)O(Rf), -L3-O—Rf, -L3-CN, - L3-N(Rf)C(O)Rf, -L3-CON(Re)(Rf), -L3-C(O)Rf, -L3-OC(O)Rf, -L3-CO2H, -L3-CO2Rf, -L3-N(Rf)C(O)N(Rf)2, -L3-S—Rf, -L3-S(O)2Rf, -L3-S(O)Rf, -L3-SO2N(Re)(Rf), -L-N(Re)(Rf), -L3-N(Rf)S(O)2Rf, and -L3-N(Rf)C(O)O(Rf); X is selected from O or NR; Ra, at each occurrence, is each independently hydrogen, C1-C6-alkyl, C1-C6-haloalkyl, or C3-C8-cycloalkyl, wherein the C3-C8-cycloalkyl is optionally substituted with 1, 2, 3, or 4 substituents selected from the group consisting of halogen, oxo, C1-C3alkyl, and C1-C3-haloalkyl; Ra1, at each occurrence, is each independently hydrogen, C1-C6-alkyl, C1-C6-haloalkyl, or C3-C8-cycloalkyl, wherein the C3-C8-cycloalkyl is optionally substituted with 1, 2, 3, or 4 substituents selected from the group consisting of halogen, oxo, C1-C3alkyl, and C1-C3-haloalkyl; Rb is each independently hydrogen, C1-C6-alkyl, or C1-C6-haloalkyl; Rb1 is each independently hydrogen, C1-C6-alkyl, or C1-C6-haloalkyl; Re, at each occurrence, is each independently hydrogen, C1-C6-alkyl, C1-C6-haloalkyl, or C3-C8-cycloalkyl, wherein the C3-C8-cycloalkyl is optionally substituted with 1, 2, 3, or 4 substituents selected from the group consisting of halogen, oxo, C1-C6-alkyl, and C1-C3-haloalkyl; Rf is each independently hydrogen, C1-C6-alkyl, or C1-C6-haloalkyl; Rg is hydrogen or C1-alkyl; L1, at each occurrence, is each independently C1-C6-alkylene or C3-C8-cycloalkyl, wherein L1 is each optionally substituted with 1, 2, 3, or 4 halogen or 1 or 2 hydroxy; L1a, at each occurrence, is each independently C1-C6-alkylene or C3-C8cycloalkyl, wherein L1a is each optionally substituted with 1, 2, 3, or 4 halogen or 1 or 2 hydroxy; and L3, at each occurrence, is each independently C1-C6-alkylene or C3-C8-cycloalkyl, wherein L3 is each optionally substituted with 1, 2, 3, or 4 halogen.