Inhibitors of fibroblast growth factor receptor and use thereof

A compound represented by general formula (I), or a pharmaceutically acceptable salt or a stereoisomer thereof:

• wherein,
• R1 and R2 are each independently selected from the group consisting of hydrogen, hydroxyl, amino, cyano, nitro, halogen atom, carboxyl, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, (C1-6 alkyl)2 amino, halo C1-6 alkyl, halo C1-6 alkoxy, C2-8 alkenyl, C2-8 alkynyl, C1-6 alkylsulfonyl, C1-6 alkylcarbonylamino, C1-6 alkyl-substituted 3-8 membered cycloalkyl, and C1-6 alkyl-substituted 3-8 membered heterocyclyl, alternatively, R1 and R2 together with two atoms on an aromatic ring or heteroaromatic ring to which they are connected respectively may form a 3-8 membered cycloalkyl, a 3-8 membered heterocyclyl, a 6-14 membered aryl or a 5-10 membered heteroaryl, and a S atom in any ring may be optionally oxidized to S(O) or S(O)2, and a carbon atom in any ring may be optionally oxidized to C(O);
• R3 and R4 are each independently selected from the group consisting of hydrogen, hydroxyl, amino, cyano, nitro, halogen atom, carboxyl, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, (C1-6 alkyl)2 amino, (C1-6 alkyl)2 amino C1-6 alkyl, halo C1-6 alkyl, halo C1-6 alkoxy, C2-8 alkenyl, C2-8 alkynyl, C1-6 alkylsulfonyl, C1-6 alkylcarbonylamino, C1-6 alkylaminocarbonyl, 3-8 membered cycloalkyl, 3-8 membered heterocyclyl, 6-14 membered aryl or 5-10 membered heteroaryl, C1-6 alkyl-substituted 3-8 membered cycloalkyl, C1-6 alkyl-substituted 3-8 membered heterocyclyl, C1-6 alkyl-substituted 6-14 membered aryl or C1-6 alkyl-substituted 5-10 membered heteroaryl;
• Ar is 6-14 membered aromatic ring group or 5-10 membered heteroaryl optionally containing 0-3 O, S and/or N atom;
• Ring A is selected from the group consisting of 3-8 membered cycloalkyl, 3-8 membered heterocyclyl, 6-14 membered aryl, and 5-10 membered heteroaryl containing 0-3 O, S and/or N atom, optionally substituted with 1-3 R5, wherein a S atom in any ring may be optionally oxidized to S(O) or S(O)2, and a carbon atom in any ring may be optionally oxidized to C(O);
• Ring B is 3-10 membered saturated or unsaturated heterocyclyl containing at least one N hetero atom or 5-6 membered N-containing heteroaryl, optionally substituted with 1-3 R6, and the N atom on ring B is directly bonded to Warhead, wherein any S atom in ring B can be optionally oxidized to S(O) or S(O)2, and any carbon atom in ring B can be optionally oxidized to C(O);
• X is N;
• R5, R6, and R7 are each independently selected from the group consisting of
• (i) hydrogen,
• (ii) hydroxyl, amino, carboxyl, cyano, nitro, halogen atom, or ═CH2,
• (iii) C1-6alkyl, C1-6 alkoxy, C1-6 alkylamino, (C1-6 alkyl)2 amino, halo C1-6 alkyl, halo C1-6 alkoxy, C2-8 alkenyl, C2-8 alkynyl, C1-6 alkylsulfonyl, or C1-6 alkylthio optionally substituted with hydroxyl, amino, carboxyl, cyano, nitro, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 alkoxy C1-6 alkoxy, C1-6 alkylamino, (C1-6 alkyl)2 amino, C1-6 alkylcarbonylamino, C1-6alkylsulfonylamino, or 3-8 membered heterocyclyl, wherein the 3-8 membered heterocyclyl may be optionally substituted with hydroxyl, amino, carboxyl, cyano, nitro, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, or (C1-6 alkyl)2 amino,
• (iv) 3-8 membered cycloalkyl or 3-8 membered heterocyclyl optionally substituted with hydroxyl, amino, carboxyl, cyano, nitro, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, or (C1-6 alkyl)2 amino, and
• (v) aminocarbonyl, cyanocarbonyl, C1-6 alkylcarbonyl, C1-6 alkylamino carbonyl, (C1-6 alkyl)2 aminocarbonyl, C1-6 alkoxycarbonyl, 3-8 membered cycloalkylcarbonyl, or 3-8 membered heterocyclyl carbonyl;
• m1 and m2 represent 1, 2 or 3, and the sum of m1 and m2 is less than or equal to 5;
• Warhead is selected from the group consisting of
• Z refers to a leaving group or an activated hydroxyl moiety,
• R11, R12, and R13 are each independently selected from the group consisting of hydrogen, halogen, cyano, C1-4 alkyl, halo C1-4 alkyl, 3-8 membered cycloalkyl, 3-8 membered heterocyclyl, 5-8 membered aryl and 5-10 membered heteroaryl, the C1-4 alkyl, halo C1-4 alkyl, 3-8 membered cycloalkyl, 3-8 membered heterocyclyl, 5-8 membered aryl or 5-10 membered heteroaryl is optionally substituted with a substituent, wherein the substituent is selected from the group consisting of hydroxyl, amino, carboxyl, cyano, nitro, halogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxy C1-4 alkoxy, C1-4 alkylamino, (C1-4 alkyl)2 amino, C1-4 alkylcarbonylamino, C1-4 alkylsulfonylamino, and 3-8 membered heterocyclyl.