Kinase inhibitors, preparation methods and uses thereof

A compound of Formula III-4, or a pharmaceutically acceptable salt thereof,

• wherein:
• R1 is hydrogen, halogen (e.g., F, Cl, or Br), CN, OH, NH2, COOH, CONH2, RA, ORA, NH(RA), N(RA)2, COORA, CONH(RA), CON(RA)2, SRA, SORA, SO2RA, or P(O)(RA)2, wherein RA at each occurrence is independently optionally substituted C1-4 alkyl, optionally substituted C2-4 alkenyl, optionally substituted C2-4 alkynyl, optionally substituted C3-6 cycloalkyl, optionally substituted 5 or 6 membered heteroaryl having 1-4 ring heteroatoms independently selected from O, S, and N, or optionally substituted 4-7 membered heterocyclyl;
• R2 is hydrogen, halogen (e.g., F, Cl, or Br), CN, OH, NH2, RB, ORB, NH(RB), or N(RB)2, wherein
• RB at each occurrence is independently an optionally substituted C1-4 alkyl, optionally substituted C2-4 alkenyl, optionally substituted C2-4 alkynyl, optionally substituted C3-6 cycloalkyl, or optionally substituted 4-7 membered heterocyclyl;
• R3 is hydrogen, optionally substituted C1-4 alkyl, or optionally substituted 3-7 membered ring, such as optionally substituted C3-6 cycloalkyl, or optionally substituted 4-7 membered heterocyclyl (such as a saturated 4-7 membered heterocyclyl);
• U is N or CR6, wherein R6 is hydrogen, halogen (e.g., F, Cl, or Br), CN, OH, NH2, RD, ORDNH(RD), N(RD)2, COOH, CONH2, COORD, CONH(RD), CON(RD)2, SRD, SORD, SO2RD, or P(O)(RD)2, wherein RD at each occurrence is independently an optionally substituted C1-4 alkyl, optionally substituted C2-4 alkenyl, optionally substituted C2-4 alkynyl, optionally substituted C3-6 cycloalkyl, optionally substituted 5 or 6 membered heteroaryl having 1-4 ring heteroatoms independently selected from O, S, and N, or optionally substituted 4-7 membered heterocyclyl;
• Y is N or CR7, wherein R7 is hydrogen, F, Cl, CN, optionally substituted C1-4 alkyl, or optionally substituted C1-4 heteroalkyl;
• Z is C(O), C(═N—OH), C(═N—O—(C1-4 alkyl)), C(═N—NH2), C(═N—NH—(C1-4 alkyl)), C(═N—N(C1-4 alkyl)(C1-4 alkyl)), SO, SO2, S(O)(═NH), or S(O)(═N—(C1-4 alkyl);
• L2 is absent, O, NH, —N(RE2)—, C(O), SO2, an optionally substituted C1-4 alkylene, an optionally substituted C2-4 alkenylene, an optionally substituted C1-4 alkynylene, optionally substituted C1-4 heteroalkylene, or an optionally substituted 3-7 membered ring, wherein RE2 is optionally substituted C1-4 alkyl or optionally substituted 3-7 membered ring;
• R30 is hydrogen, an optionally substituted phenyl, optionally substituted 5 or 6 membered heteroaryl, or optionally substituted 8-12 membered ring having two or more rings;
• R9 at each occurrence is independently RN, COORN, CORN, CONH(RN), or CON(RN)2, wherein RN at each occurrence is independently an optionally substituted C1-4 alkyl, optionally substituted C2-4 alkenyl, optionally substituted C2-4 alkynyl, optionally substituted C3-6 cycloalkyl, optionally substituted phenyl, or optionally substituted 5 or 6 membered heteroaryl;
• and
• n1 is 0, 1, 2, or 3.