Protein kinase inhibitors and uses thereof

A compound or pharmaceutically acceptable salt thereof, wherein the compound is chosen from:

• N-(5-((8-(4-fluoro-2-isopropoxyphenyl)quinazolin-2-yl)amino)-2-methylphenyl)-1-methylpiperidine-4-carboxamide;
• or
• (S)—N-(5-((8-(4-fluoro-2-isopropoxyphenyl)quinazolin-2-yl)amino)-2-methylphenyl)-1-methylpyrrolidine-2-carboxamide;
• or
• N-(5-((8-(4-fluoro-2-isopropoxyphenyl)quinazolin-2-yl)amino)-2-methylphenyl)-1-methylazetidine-3-carboxamide;
• or
• N-(5-((8-(4-fluoro-2-isopropoxyphenyl)quinazolin-2-yl)amino)-2-methylphenyl)tetrahydro-2H-pyran-4-carboxamide;
• or
• (R)—N-(5-((8-(4-fluoro-2-isopropoxyphenyl)quinazolin-2-yl)amino)-2-methylphenyl)-1-methylpyrrolidine-2-carboxamide;
• or
• N-(5-((8-(4-fluoro-2-isopropoxyphenyl)quinazolin-2-yl)amino)-2-methylphenyl)-2-(4-methylpiperazin-1-yl)acetamide;
• or
• N-(5-((8-(4-fluoro-2-isopropoxyphenyl)quinazolin-2-yl)amino)-2-methylphenyl)-4-methylpiperazine-1-carboxamide.

A compound of Formula A1 or Formula A2:

• or a pharmaceutically acceptable salt, amide or ester thereof, wherein:
• R1, R2, R3 and R4 each independently is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted heteroalkyl, optionally substituted haloalkyl, optionally substituted deuteroalkyl, optionally substituted alkylthio, optionally substituted alkylamino, optionally substituted hydroxyalkyl, optionally substituted mercaptoalkyl, optionally substituted aminoalkyl, —C(O)Rz, —C(O)OH, —C(O)ORu, —B(OH)2, hydroxy, halo, cyano, nitro, amino or amido;
• Y is —N(Rb)C(O)—RY, —C(O)N(Rb)—RYA, —N(Rb)—CH2—RY;
• —CH2—N(Rb)RY, —N(Ra)C(O)—RV—N(Rb)RY, —N(Rb)C(O)—RV—RY, —N(Ra)Rb or of Formula F;
• Ra is hydrogen, optionally substituted alkyl, optionally substituted alkynyl or of Formula F:
• Rb is hydrogen or optionally substituted alkyl;
• RV is an optionally substituted alkylene;
• RY is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted heteroalkyl, optionally substituted haloalkyl, optionally substituted deuteroalkyl, optionally substituted hydroxyalkyl, optionally substituted mercaptoalkyl, optionally substituted aminoalkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkylalkyl, optionally substituted aryl, optionally substituted arylaminoalkyl, optionally substituted aryloxyalkyl, optionally substituted arylthioalkyl or optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylaminoalkyl, optionally substituted heteroaryloxyalkyl, optionally substituted heteroarylthioalkyl, optionally substituted heteroarylalkyl or is of Formula F;
• RYA is an optionally substituted aryl, optionally substituted arylaminoalkyl, optionally substituted aryloxyalkyl, optionally substituted arylthioalkyl or optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylaminoalkyl, optionally substituted heteroaryloxyalkyl, optionally substituted heteroarylthioalkyl or optionally substituted heteroarylalkyl;
• Z1 is an optionally substituted heterocycloalkyl, Xa is C(R43)R43A;
• Xb is C(R44)R44A;
• Xc is C(R45)R45A, N—R45B, O, S, S(O) or SO2;
• Xd is C(R46)R46A;
• and Xe is C(R47)R47A;
• and R43, R44, R45, R46, R47, R43A, R44A, R45A, R46A, R47A and R45B each independently is hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkoxy, optionally substituted C1-C6 heteroalkyl, optionally substituted C1-C6 haloalkyl, optionally substituted C1-C6 deuteroalkyl, optionally substituted C1-C6 alkylthio, optionally substituted C1-C6 alkylamino, optionally substituted C1-C6 hydroxyalkyl, optionally substituted C1-C6 mercaptoalkyl, optionally substituted C1-C6 aminoalkyl;
• R10, R11, R12 and R13 each independently is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted heteroalkyl, optionally substituted haloalkyl, optionally substituted deuteroalkyl, optionally substituted alkylthio, optionally substituted alkylamino, optionally substituted hydroxyalkyl, optionally substituted mercaptoalkyl, optionally substituted aminoalkyl, —C(O)Rz, —C(O)OH, —C(O)ORu, —B(OH)2, hydroxy, halo, cyano, nitro, amino, amido, RW or —W—RW;
• RW is an optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkylalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylaminoalkyl, optionally substituted aryloxyalkyl, optionally substituted arylthioalkyl, optionally substituted heteroarylaminoalkyl, optionally substituted heteroaryloxyalkyl, optionally substituted heteroarylthioalkyl, optionally substituted arylalkyl or optionally substituted heteroarylalkyl;
• W is an optionally substituted alkylene, optionally substituted alkynyl, amino, amido, —O—, —S—, —S(O)— or —SO2—;
• Rz is hydrogen or Ru;
• and
• Ru is an optionally substituted alkyl, optionally substituted hydroxyalkyl, optionally substituted mercaptoalkyl, optionally substituted aminoalkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylaminoalkyl, optionally substituted aryloxyalkyl, optionally substituted arylthioalkyl, optionally substituted heteroarylaminoalkyl, optionally substituted heteroaryloxyalkyl, optionally substituted heteroarylthioalkyl, optionally substituted arylalkyl or optionally substituted heteroarylalkyl;
• with the proviso that the compound is not of Formula X1, not of Formula X2, not of Formula X3 and not of Formula X4:
• wherein:
• R2X, R3X and R4X each independently is hydrogen, optionally substituted C1-C4 alkyl or optionally substituted C1-C4 alkoxy;
• R14X, R15X, R16X and R17X each independently is hydrogen, optionally substituted C1-C4 alkyl, optionally substituted C1-C4 alkoxy, or halo;
• R19X, R21X and R22X each independently is hydrogen or optionally substituted C1-C6 alkyl;
• m is an integer of 1 or 2;
• RYX is methyl or
• n is an integer of 1 to 10;
• and RYXX is hydrogen, optionally substituted alkyl or optionally substituted amidoalkyl.