Protein tyrosine kinase inhibitor and medical use thereof

A compound or a pharmaceutically acceptable salt, stereoisomer, ester, prodrug, solvate, and deuterated compound thereof, wherein said compound has a structure of:

• wherein,
• Ring A is a 5-7 membered heteroaromatic ring;
• Ring B is a C6-C10 aromatic ring or a 5-10 membered heterocyclic ring;
• optionally, said C6-C10 aromatic ring or 5-10 membered heterocyclic ring may be fused with a C6-C10 aromatic ring, a C5-C8 aliphatic ring, or a 5-10 membered heterocyclic ring;
• X1 is O or S;
• Y is —N(C0-C10 alkyl)(C0-C10 alkyl) or —O(C0-C10 alkyl);
• L1 is selected from:
• a single bond, —C(O)—, —C(O)O—, —C(O)NR3—, —C(O)N(R3)O—, —S(O)2—, —S(O)2NR3—, —S(O)—, —S(O)NR3—, -Cy-;
• -Cy- is selected from:
• substituted or unsubstituted cycloalkylene, substituted or unsubstituted arylene, and substituted or unsubstituted heterocyclylene;
• L2 is a single bond or alkylene, wherein one or more methylene units in alkylene are optionally and independently substituted by a group selected from:
• —N(R4)—, —N(R4)C(O)—, —C(O)N(R4)—, —N(R4)S(O)2—, —S(O)2N(R4)—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —S—, —S(O)— or —S(O)2;
• wherein, a and b are independently integers from 0 to 10, and RL201 and RL202 are independently selected from:
• H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, azido, —ORL203, —C(O)RL203, —C(O)ORL203, —NRL204C(O)ORL203, —OC(O)RL203, —NRL204SO2RL203, —SO2NRL203RL204, —NRL204C(O)RL203, —C(O)NRL203RL204, —NRL203RL204, —SRL203, —S(O)RL203, —S(O)2RL203, —SO3H, C3-C6 cycloalkyl, cycloalkyl alkyl, heterocyclyl, heterocyclylalkyl;
• wherein, RL203 and RL204 are independently selected from:
• H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkyl alkyl, substituted or unsubstituted heterocyclyl, and substituted or unsubstituted heterocyclylalkyl;
• L3 is alkylene, wherein one or more methylene units in alkylene are optionally and independently substituted by a group selected from:
• —N(R5)—, —N(R5)C(O)—, —C(O)N(R5)—, —N(R5)S(O)2—, —S(O)2N(R5)—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —S—, —S(O)— or —S(O)2;
• wherein, c and d are independently integers from 0 to 10, and RL301 and RL302 are independently selected from:
• H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, azido, —ORL303, —C(O)RL303, —C(O)ORL303, —NRL304C(O)ORL303, —OC(O)RL303, —NRL304SO2RL303, —SO2NRL303RL304, —NRL304C(O)RL303, —C(O)NRL303RL304, —NRL303RL304, —SRL303, —S(O)RL303, —S(O)2RL303, —SO3H, C3-C6 cycloalkyl, cycloalkyl alkyl, heterocyclyl, heterocyclylalkyl;
• wherein, RL303 and RL304 are independently selected from:
• H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkyl alkyl, substituted or unsubstituted heterocyclyl, and substituted or unsubstituted heterocyclylalkyl;
• R3 to R5 are each independently selected from:
• H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkyl alkyl, substituted or unsubstituted heterocyclyl, and substituted or unsubstituted heterocyclylalkyl, wherein said alkyl, cycloalkyl, or heterocyclyl is optionally substituted by a group selected from:
• halogen, cyano, nitro, azido, —OR′, —C(O)R′, —C(O)OR′, —OC(O)R′, —NR′C(O)OR″, —NR′SO2R″, —SO2NR′R″, —NR′C(O)R″, —C(O)NR′R″, —NR′R″, —SR′, —SOR′, —SO2R′, —SO3H, C1-C10 alkyl, C1-C10 haloalkyl, C1-C10 silyl, C3-C10 cycloalkyl, phenyl, 4-10 membered heterocyclyl;
• R1 is one or more independent substituents on Ring B, each R1 is independently selected from:
• H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, azido, —OR101, —C(O)R101, —C(O)OR101, —NR102C(O)OR101, —OC(O)R101, —NR102SO2R101, —SO2NR101R102, —NR102C(O)R101, —C(O)NR101R102, —NR101R102, —S(O)jtR101, where j is an integer from 0 to 2, —SO3H, —NR102(CR103R104)tOR101, —(CH2)t(C6-C10 aryl), —SO2(CH2)t(C6-C10 aryl), —S(CH2)t(C6-C10 aryl), —O(CH2)t(C6-C10 aryl), —(CH2)t(4-10 membered heterocyclyl), —SO2(CH2)t(4-10 membered heterocyclyl), —S(CH2)t(4-10 membered heterocyclyl), —O(CH2)t(4-10 membered heterocyclyl), —(CH2)t(C3-C10 cycloalkyl), —SO2(CH2)t(C3-C10 cycloalkyl), —S(CH2)t(C3-C10 cycloalkyl), —O(CH2)t(C3-C10 cycloalkyl), where t is an integer from 0 to 5;
• wherein, said C1-C10 alkyl, C6-C10 aryl, or 4-10 membered heterocyclyl is optionally substituted by a group selected from:
• halogen, cyano, nitro, azido, —OR′, —C(O)R′, —C(O)OR′, —OC(O)R′, —NR′C(O)OR″, —NR′SO2R″, —SO2NR′R″, —NR′C(O)R″, —C(O)NR′R″, —NR′R″, —SR′, —SOR′, —SO2R′, —SO3H, C1-C10 alkyl, C1-C10 haloalkyl, C1-C10 silyl, C3-C10 cycloalkyl, phenyl, and 4-10 membered heterocyclyl;
• R101 to R104 are each independently selected from:
• H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkyl alkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heterocyclylalkyl, and C1-C10 silyl;
• wherein said alkyl, cycloalkyl, or heterocyclyl is optionally substituted by a group selected from:
• halogen, cyano, nitro, azido, —OR′, —C(O)R′, —C(O)OR′, —OC(O)R′, —NR′C(O)OR″, —NR′SO2R″, —SO2NR′R″, —NR′C(O)R″, —C(O)NR′R″, —NR′R″, —SR′, —SOR′, —SO2R′, —SO3H, C1-C10 alkyl, C1-C10 haloalkyl, C1-C10 silyl, C3-C10 cycloalkyl, phenyl, and 4-10 membered heterocyclyl;
• m is an integer from 1 to 5 (for example, 1, 2, 3, 4, or 5, where valency permits);
• R0 is selected from:
• H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, azido, —OR001, —C(O)R001, —C(O)OR001, —NR002C(O)OR001, —OC(O)R001, —NR002SO2R001, —SO2NR001R002, —NR002C(O)R001, —C(O)NR001R002, —NR001R002, —S(O)iR002 (where i is an integer from 0 to 2), —SO3H, —NR002 (CR003R004)tOR001, and
• wherein, Ring E is a C6-C10 aromatic ring or a 4-10 membered heterocyclic ring;
• optionally, said C6-C10 aromatic ring or 4-10 membered heterocyclic ring may be fused with a C6-C10 aromatic ring, a C5-C8 aliphatic ring, or a 4-10 membered heterocyclic ring;
• R2 is selected from:
• H, ═O, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, azido, —OR201, —C(O)R201, —C(O)OR201, —NR202C(O)OR201, —OC(O)R201, —NR202SO2R201, —SO2NR201R202, —NR202C(O)R201, —C(O)NR201R202, —NR201R202, —S(O)iR201, where i is an integer from 0 to 2, —SO3H, —(CH2)j(C6-C10 aryl), —SO2(CH2)j(C6-C10 aryl), —S(CH2)j(C6-C10 aryl), —O(CH2)j(C6-C10 aryl), —(CH2)j(4-10 membered heterocyclyl), —SO2(CH2)j(4-10 membered heterocyclyl), —S(CH2)j(4-10 membered heterocyclyl), —O(CH2)j(4-10 membered heterocyclyl), —(CH2)j(C3-C10 cycloalkyl), —SO2(CH2)j(C3-C10 cycloalkyl), —S(CH2)j(C3-C10 cycloalkyl), and —O(CH2)j(C3-C10 cycloalkyl), where j is an integer from 0 to 5;
• wherein, said C1-C10 alkyl, C6-C10 aryl, or 4-10 membered heterocyclyl is optionally substituted by a group selected from:
• halogen, cyano, nitro, azido, —OR′, —C(O)R′, —C(O)OR′, —OC(O)R′, —NR′C(O)OR″, —NR′SO2R″, —SO2NR′R″, —NR′C(O)R″, —C(O)NR′R″, —NR′R″, —SR′, —SOR′, —SO2R′, —SO3H, C3-C10 cycloalkyl, phenyl, and 4-10 membered heterocyclyl;
• n is an integer from 1 to 5 (for example, 1, 2, 3, 4, or 5, where valency permits);
• R001 to R004 are each independently selected from:
• H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkyl alkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heterocyclylalkyl, and C1-C10 silyl, wherein said alkyl, cycloalkyl, or heterocyclyl is optionally substituted by a group selected from:
• halogen, cyano, nitro, azido, —OR′, —C(O)R′, —C(O)OR′, —OC(O)R′, —NR′C(O)OR″, —NR′SO2R″, —SO2NR′R″, —NR′C(O)R″, —C(O)NR′R″, —NR′R″, —SR′, —SOR′, —SO2R′, —SO3H, C1-C10 alkyl, C1-C10 haloalkyl, C1-C10 silyl, C3-C10 cycloalkyl, phenyl, and 4-10 membered heterocyclyl;
• R201 to R204 are each independently selected from:
• H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkyl alkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heterocyclylalkyl, and C1-C10 silyl, wherein said alkyl, cycloalkyl, or heterocyclyl is optionally substituted by a group selected from:
• halogen, cyano, nitro, azido, —OR′, —C(O)R′, —C(O)OR′, —OC(O)R′, —NR′C(O)OR″, —NR′SO2R″, —SO2NR′R″, —NR′C(O)R″, —C(O)NR′R″, —NR′R″, —SR′, —SOR′, —SO2R′, —SO3H, C1-C10 alkyl, C1-C10 haloalkyl, C1-C10 silyl, C3-C10 cycloalkyl, phenyl, and 4-10 membered heterocyclyl;
• and
• R′ and R″ are independently selected from:
• H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkyl alkyl, substituted or unsubstituted heterocyclyl, and substituted or unsubstituted heterocyclylalkyl.