| 摘要 |
Disclosed are compounds of Formula 1,;
and pharmaceutically acceptable salts thereof, wherein G, L1, L2, R1, R2, R3, and R4 are defined in the specification. This disclosure also relates to materials and methods for preparing compounds of Formula 1, pharmaceutical compositions containing them, and their use for treating disorders, diseases, and conditions involving the immune system and inflammation, including rheumatoid arthritis, hematological malignancies, epithelial cancers (i.e., carcinomas), and other disorders, diseases, and conditions for which inhibition of SYK is indicated. |
| 主权项 |
1. A method of treating a disease or condition by inhibiting SYK in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of Formula 1, or a pharmaceutically acceptable salt thereof, wherein: G is C(R5); L1 and L2 are each independently selected from —NH— and a bond; R1 and R2 are each independently selected from hydrogen, halo, C1-3 alkyl, and C1-3 haloalkyl, or R1 and R2, together with the atom to which they are attached, form a C3-6 cycloalkyl; R3 is selected from C2-6 alkyl, C3-8 cycloalkyl, C2-5 heterocyclyl, and C1-9 heteroaryl, each optionally substituted with from one to five substituents independently selected from halo, oxo, —NO2, —CN, R6, and R7; R4 is selected from C3-8 cycloalkyl, C2-5 heterocyclyl, C6-14 aryl, and C1-9 heteroaryl, each optionally substituted with from one to five substituents independently selected from halo, oxo, —CN, R6, and R7; R5 is selected from hydrogen, halo, —CN, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C2-5 heterocyclyl, C1-5 heteroaryl, and R10, wherein the alkyl, alkenyl, alkynyl moieties are each optionally substituted with from one to five substituents independently selected from halo, —CN, oxo, and R10, and wherein the heterocyclyl moiety has 3 to 6 ring atoms and the heteroaryl moiety has 5 or 6 ring atoms, and the heterocyclyl and heteroaryl moieties are each optionally substituted with from one to four substituents independently selected from halo, —NO2, —CN, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, and R10; each R6 is independently selected from —OR8, —N(R8)R9, —NR8C(O)R9, —C(O)R8, —C(O)OR8, —C(O)N(R8)R9, —C(O)N(R8)OR9, —C(O)N(R8)S(O)2R9, —N(R8)S(O)2R9, —S(O)nR8, and —S(O)2N(R8)R9; each R7 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl-(CH2)m—, C6-14 aryl-(CH2)m—, C2-5 heterocyclyl-(CH2)m—, and C1-9 heteroaryl-(CH2)m—, each optionally substituted with from one to five substituents independently selected from halo, oxo, —NO2, —CN, C1-6 alkyl, C1-6 haloalkyl, and R10; each R8 and R9 is independently selected from hydrogen or from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl-(CH2)m—, C6-14 aryl-(CH2)m—, C2-5 heterocyclyl-(CH2)m—, and C1-9 heteroaryl-(CH2)m—, each optionally substituted with from one to five substituents independently selected from halo, oxo, —NO2, —CN, C1-6 alkyl, C1-6 haloalkyl, and R10; each R10 is independently selected from —OR11, —N(R11)R12, —N(R11)C(O)R12, —C(O)R11, —C(O)OR11, —C(O)N(R11)R12, —C(O) N(R11)OR12, —C(O)N(R11)S(O)2R12, —NR11S(O)2R12, —S(O)nR11, and —S(O)2N(R11)R12; each R11 and R12 is independently selected from hydrogen and C1-6 alkyl; each n is independently selected from 0, 1 and 2; and each m is independently selected from 0, 1, 2, 3, and 4; wherein each of the aforementioned heteroaryl moieties has one to four heteroatoms independently selected from N, O, and S, and each of the aforementioned heterocyclyl moieties is saturated or partially unsaturated and has one or two heteroatoms independently selected from N, O, and S. |
