Substituted pyrazinecarboxamide compounds for treating diseases related to EGFR mutation

A compound having a structure of general formula (1), or an isomer, a crystalline form, a pharmaceutically acceptable salt, a hydrate or a solvate thereof:

• wherein, in general formula (1):
• Y is
• L1 is —O— or —NH—;
• X is a C6-C14 arylene or a 5-11 membered heteroarylene, wherein the arylene and the heteroarylene may be optionally substituted with one or more of the following groups:
• —H, a halogen, a C1-C6 alkyl, a C3-C6 cycloalkyl, a C1-C6 alkoxy and a C1-C6 haloalkoxy;
• R1 is —H, a halogen, —(CH2)nNR6R7, —NR6R7, —O(CH2)mNR6R7, —N(R5)(CH2)mNR6R7, a C1-C6 alkoxy, a —CH2-3-15 membered heterocycloalkyl or a 3-15 membered heterocycloalkyl, wherein the alkoxy and the heterocycloalkyl may be optionally substituted with one or more of the following groups:
• —H, —R4, —(CH2)nNR6R7, —NR6R7, —O(CH2)mNR6R7, —N(R5)(CH2)mNR6R7 and —R3;
• L2 is —O—, —NH— or a chemical bond;
• R2 is a C1-C6 alkyl, a C3-C14 cycloalkyl, a C6-C14 aryl, a 3-4 membered heterocycloalkyl,
• or a 6-11 membered heterocycloalkyl;
• wherein the alkyl, the cycloalkyl, the aryl, the heterocycloalkyl,
• may be optionally substituted with one or more of the following groups:
• —H, a halogen, —R4, —(CH2)nOR4—, —(CH2)nNR4R5—, —OR4, —NR4R5, —CN, —C(O)NR4R5, —NR5C(O)R4, —NR5S(O)2R4, —S(O)pR4 and —S(O)2NR4R5;
• R3 is a 3-11 membered heterocycloalkyl, wherein the heterocycloalkyl may be optionally substituted with one or more of the following groups:
• —H, —CD3, —R4, —OR4 and —NR4R5;
• R4 and R5 are each independently —H, a C1-C6 alkyl or a C3-C14 cycloalkyl;
• R6 and R7 are each independently —H, a C1-C6 alkyl or a C3-C14 cycloalkyl, or R6 and R7 form a 3-11 membered heterocycloalkyl along with N atoms connected thereto, wherein the heterocycloalkyl may be optionally substituted with one or more of the following groups:
• —H, —CD3, a halogen, —R4 and —OR4;
• R0 is a C1-C6 alkyl or a C3-C14 cycloalkyl;
• and
• p is an integer of 0, 1 or 2, n is an integer of 0, 1, 2 or 3, and m is an integer of 1, 2 or 3;
• or
• Y is
• L1 is —O— or —NH—;
• X is a C6-C14 arylene or a 5-11 membered heteroarylene, wherein the arylene and the heteroarylene may be optionally substituted with one or more of the following groups:
• —H, a halogen, a C1-C6 alkyl, a C3-C6 cycloalkyl, a C1-C6 alkoxy and a C1-C6 haloalkoxy;
• R1 is —H, a halogen, —(CH2)nNR6R7, —NR6R7, —O(CH2)mNR6R7, —N(R5)(CH2)mNR6R7, a C1-C6 alkoxy, a —CH2-3-15 membered heterocycloalkyl or a 3-15 membered heterocycloalkyl, wherein the alkoxy and the heterocycloalkyl may be optionally substituted with one or more of the following groups:
• —H, —R4, —(CH2)nNR6R7, —NR6R7, —O(CH2)mNR6R7, —N(R5)(CH2)mNR6R7 and —R3;
• L2 is —O—, —NH— or a chemical bond;
• R2 is a C1-C6 alkyl, a C3-C14 cycloalkyl, a C6-C14 aryl, a 3-4 membered heterocycloalkyl,
• or a 6-11 membered heterocycloalkyl;
• wherein the alkyl, the cycloalkyl, the aryl, the heterocycloalkyl,
• may be optionally substituted with one or more of the following groups:
• —H, a halogen, —R4, —(CH2)nOR4—, —(CH2)nNR4R5—, —OR4, —NR4R5, —CN, —C(O)NR4R5, —NR5C(O)R4, —NR5S(O)2R4, —S(O)pR4 and —S(O)2NR4R5;
• R3 is a 3-11 membered heterocycloalkyl, wherein the heterocycloalkyl may be optionally substituted with one or more of the following groups:
• —H, —CD3, —R4, —OR4 and —NR4R5;
• R4 and R5 are each independently —H, a C1-C6 alkyl or a C3-C14 cycloalkyl;
• R6 and R7 are each independently —H, a C1-C6 alkyl or a C3-C14 cycloalkyl, or R6 and R7 form a 3-11 membered heterocycloalkyl along with N atoms connected thereto, wherein the heterocycloalkyl may be optionally substituted with one or more of the following groups:
• —H, —CD3, a halogen, —R4 and —OR4;
• and
• p is an integer of 0, 1 or 2, n is an integer of 0, 1, 2 or 3, and m is an integer of 1, 2 or 3.