AZAINDOLE DERIVATIVES

摘要

Disclosed are compounds of Formula 1,;;and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are defined in the specification. This disclosure also relates to materials and methods for preparing compounds of Formula 1, to pharmaceutical compositions which contain them, and to their use for treating immunological disorders, cardiovascular disease, cancer, and other diseases, disorders or conditions associated with PI3Kδ.

主权项

1. A method of treating a disease, disorder or condition in a subject, the method comprising administering to the subject an effective amount of a compound of Formula 1, or a pharmaceutically acceptable salt thereof, wherein: R1 is selected from C3-8 cycloalkyl, C2-6 heterocyclyl, C6-14 aryl, and C1-9 heteroaryl, each optionally substituted with from one to five substituents independently selected from halo, oxo, —CN, R11, and R12; R2, R4, and R5 are each independently selected from hydrogen, halo, —OH, —CN, C1-3 alkyl, and C1-3 haloalkyl; R3 is selected from hydrogen, C1-3 alkyl, and C1-3 haloalkyl; R6 and R7 are each independently selected from hydrogen, C1-3 alkyl, and C1-3 haloalkyl; R8 is selected from hydrogen, methyl, and —NH2; R9 is selected from hydrogen, halo, —CN, C1-3 haloalkyl, —OR16, —C(O)R16, —C(O)OR16, —C(O)N(R16)R17, —C(O)N(R16)OR17, —C(O)N(R16)S(O)2R18, —SR16, —S(O)R18, —S(O)2R18, and —S(O)2N(R16)R17; or R8 is selected from —NH— and —CH2—, and R8 and R9, together with the carbon atoms to which they are attached, form a C2-4 heteroarylene having 5 ring atoms and 1 to 3 heteroatoms, each of the heteroatoms being nitrogen, and wherein the C2-4 heteroarylene is optionally substituted with R12; R10 is selected from halo, —OH, C1-3 alkyl, —NHR16, and —NHC(O)R16; each R11 is independently selected from —OR13, —N(R13)R14, —NR13C(O)R14, —NHC(O)NR13R14, —NR13C(O)NHR14, —C(O)R13, —C(O)OR13, —C(O)N(R13)R14, —C(O)N(R13)OR14, —C(O)N(R13)S(O)2R12, —N(R13)S(O)2R12, —SR13, —S(O)R12, —S(O)2R12, and —S(O)2N(R13)R14; each R12 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl-(CH2)m—, C6-14 aryl-(CH2)m—, C2-6 heterocyclyl-(CH2)m—, and C1-9 heteroaryl-(CH2)m—, each optionally substituted with from one to five substituents independently selected from halo, oxo, —CN, C1-6 alkyl, C1-6 haloalkyl, and R15; each R13 and R14 is independently selected from
(a) hydrogen; and(b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl-(CH2)m—, C6-14 aryl-(CH2)m—, C2-6 heterocyclyl-(CH2)m—, and C1-9 heteroaryl-(CH2)m—, each optionally substituted with from one to five substituents independently selected from halo, oxo, —CN, C1-6 alkyl, C1-6 haloalkyl, and R′5; each R15 is independently selected
from —OR16, —N(R16)R17, —N(R16)C(O)R17, —NHC(O)NR16R17, —NR16C(O)NHR17, —C(O)R16, —C(O)OR16, —C(O)N(R16)R17, —C(O)N(R16)OR17, —C(O)N(R16)S(O)2R18, —NR16S(O)2R18, —SR16, —S(O)R18, —S(O)2R18, and —S(O)2N(R16)R17; each R16 and R17 is independently selected from hydrogen, C1-6 alkyl, and C3-6 cycloalkyl; each R18 is independently selected from C1-6 alkyl and C3-6 cycloalkyl; each m is independently selected from 0, 1, 2, 3, and 4; wherein each of the aforementioned heteroaryl moieties independently has 1 to 4 heteroatoms independently selected from N, O, and S, and each of the aforementioned heterocyclyl moieties independently has 1 to 4 heteroatoms independently selected from N, O, and S; and wherein the disease, disorder or condition is selected from allergic rhinitis, asthma, atopic dermatitis, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, psoriasis, immune thrombocytopenic purpura, inflammatory bowel disease, behcet's disease, graft-versus-host disease (GVHD), chronic obstructive pulmonary disease, atherosclerosis, myocardial infarction, and thrombosis.