Benzo[b]selenophene sting regulator, preparation method and use thereof

A compound selected from the following formulas, stereoisomers or pharmaceutically acceptable salts thereof:

• Code
• Structural formula
• I-1
• I-2
• I-3
• I-4
• I-5
• I-6
• I-7
• I-8
• I-9
• I-10
• I-11
• I-12
• I-13
• I-14
• I-15
• I-16
• I-17
• I-18
• I-19
• I-20
• I-21
• I-22
• I-23
• I-24

A drug composition comprising an active component and a pharmaceutically acceptable accessory;

• wherein the active component comprises a pharmaceutically effective amount of a compound, or a stereoisomer thereof or one or more of pharmaceutically acceptable salts thereof,
• wherein the compound is shown in general formula (I):
• where
• R1 is selected from H, halo, cyano, nitro, OR6, N(R6)2, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl substituted with OR6 or C1-C6 alkyl substituted with N(R6)2;
• R2 is selected from halo, cyano, nitro, OR6, SR6, N(R6)2, COOR6, C(O)N(R6)2, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl substituted with OR6, C1-C6 alkyl substituted with N(R6)2, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl(enyl) or C3-C6 cycloalkyl;
• R3 is selected from halo, cyano, nitro, OR6, SR6, N(R6)2, COOR6, C(O)N(R6)2, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl substituted with OR6, and C1-C6 alkyl substituted with N(R6)2, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl(enyl) or C3-C6 cycloalkyl;
• or R2 and R3, together with atoms to which they are attached, can form a 5- or 6-membered heterocycle comprising one to two members selected from O, S or N ring members,
• R4 is selected from H, halo, cyano, nitro, OR6, N(R6)2, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl substituted with OR6 or C1-C6 alkyl substituted with N(R6)2;
• R5 is selected from H, halo, cyano, C1-C6 alkyl, C1-C6 haloalkyl and C3-C6 cycloalkyl;
• R6 on the same atom is identical or different, R6 on different atoms are identical or different, and each R6 is independently selected from H, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C8 heterocyclyl or C5-C10 aryl;
• X1 is C(O);
• X2 is (C(R7)2)(1-3);
• R7 on the same atom is identical or different, R7 on different atoms are identical or different, and each R7 is independently selected from H, halo, CN, OR6, N(R6)2, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl substituted with OR6 or C3-C6 cycloalkyl;
• or two R7 on different carbon atoms, together with atoms to which they are attached, can form a 3- to 6-membered ring;
• or two R7 on a single carbon atom, together with atoms to which they are attached, can form a 3- to 6-membered ring;
• and
• X3 is selected from COOR6, C(O)N(R6)2, C(O)NHOH, SO2R6, S(O)NR6 or C(CF3)2OR6.

A method of activating a cGAS-STING pathway in a subject in need thereof, comprising administering a compound, a stereoisomer or a pharmaceutically acceptable salt thereof to the subject,

• wherein the compound is shown in general formula (I):
• where
• R1 is selected from H, halo, cyano, nitro, OR6, N(R6)2, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl substituted with OR6 or C1-C6 alkyl substituted with N(R6)2;
• R2 is selected from halo, cyano, nitro, OR6, SR6, N(R6)2, COOR6, C(O)N(R6)2, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl substituted with OR6, C1-C6 alkyl substituted with N(R6)2, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl(enyl) or C3-C6 cycloalkyl;
• R3 is selected from halo, cyano, nitro, OR6, SR6, N(R6)2, COOR6, C(O)N(R6)2, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl substituted with OR6, and C1-C6 alkyl substituted with N(R6)2, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl(enyl) or C3-C6 cycloalkyl;
• or R2 and R3, together with atoms to which they are attached, can form a 5- or 6-membered heterocycle comprising one to two members selected from O, S or N ring members,
• R4 is selected from H, halo, cyano, nitro, OR6, N(R6)2, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl substituted with OR6 or C1-C6 alkyl substituted with N(R6)2;
• R5 is selected from H, halo, cyano, C1-C6 alkyl, C1-C6 haloalkyl and C3-C6 cycloalkyl;
• R6 on the same atom is identical or different, R6 on different atoms are identical or different, and each R6 is independently selected from H, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C8 heterocyclyl or C5-C10 aryl;
• X1 is C(O);
• X2 is (C(R7)2)(1-3);
• R7 on the same atom is identical or different, R7 on different atoms are identical or different, and each R7 is independently selected from H, halo, CN, OR6, N(R6)2, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl substituted with OR6 or C3-C6 cycloalkyl;
• or two R7 on different carbon atoms, together with atoms to which they are attached, can form a 3- to 6-membered ring;
• or two R7 on a single carbon atom, together with atoms to which they are attached, can form a 3- to 6-membered ring;
• and
• X3 is selected from COOR6, C(O)N(R6)2, C(O)NHOH, SO2R6, S(O)NR6 or C(CF3)2OR6.

A method comprising administering a compound, a stereoisomer or a pharmaceutically acceptable salt thereof to a subject in need of treatment of a disease related to activity of a STING pathway,

• wherein the compound is shown in general formula (I):
• where
• R1 is selected from H, halo, cyano, nitro, OR6, N(R6)2, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl substituted with OR6 or C1-C6 alkyl substituted with N(R6)2;
• R2 is selected from halo, cyano, nitro, OR6, SR6, N(R6)2, COOR6, C(O)N(R6)2, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl substituted with OR6, C1-C6 alkyl substituted with N(R6)2, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl(enyl) or C3-C6 cycloalkyl;
• R3 is selected from halo, cyano, nitro, OR6, SR6, N(R6)2, COOR6, C(O)N(R6)2, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl substituted with OR6, and C1-C6 alkyl substituted with N(R6)2, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl(enyl) or C3-C6cycloalkyl;
• or R2 and R3, together with atoms to which they are attached, can form a 5- or 6-membered heterocycle comprising one to two members selected from O, S or N ring members;
• R4 is selected from H, halo, cyano, nitro, OR6, N(R6)2, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl substituted with OR6 or C1-C6 alkyl substituted with N(R6)2;
• R5 is selected from H, halo, cyano, C1-C6 alkyl, C1-C6 haloalkyl and C3-C6 cycloalkyl;
• R6 on the same atom is identical or different, R6 on different atoms are identical or different, and each R6 is independently selected from H, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C8 heterocyclyl or C5-C10 aryl;
• X1 is C(O);
• X2 is (C(R7)2)(1-3);
• R7 on the same atom is identical or different, R7 on different atoms are identical or different, and each R7 is independently selected from H, halo, CN, OR6, N(R6)2, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl substituted with OR6 or C3-C6 cycloalkyl;
• or two R7 on different carbon atoms, together with atoms to which they are attached, can form a 3- to 6-membered ring;
• or two R7 on a single carbon atom, together with atoms to which they are attached, can form a 3- to 6-membered ring;
• and
• X3 is selected from COOR6, C(O)N(R6)2, C(O)NHOH, SO2R6, S(O)NR6 or C(CF3)2OR6.