Heterocyclic compounds as mutant idh inhibitors

A compound of Formula (IA):

• or a salt, polymorph, solvate, enantiomer, stereoisomer or tautomer thereof, wherein
• wherein,
• X is O, S, NRa or CRbRc;
• A is C6-C10 aryl, 5- to 10 membered heteroaryl, C3-C8 cycloalkyl or 3- to 10-membered heterocyclyl, wherein each of which is optionally substituted by R6a;
• B is hydrogen, C6-C10 aryl, 5- to 10-membered heteroaryl, C3-C8 cycloalkyl or 3- to 10-membered heterocyclyl, wherein each of which is optionally substituted by R6b;
• L is a bond, —O—, —(CH2)1-3—, —NH—, —NCH3—, —SO2—, —C(O)—, —CH2—O—, —S—, —CRbRc—, —C(O)NH— or —NHC(O)—;
• Ra is hydrogen or C1-C6 alkyl optionally substituted by oxo, —OH or halogen;
• Rb and Rc are independently hydrogen, halogen, —CN, C1-C6 alkyl, C3-C6 cycloalkyl, or —(C1-C3 alkylene)(C3-C6 cycloalkyl);
• R1 is hydrogen, halogen or C1-C6 alkyl;
• R2 is hydrogen, halogen, C1-C6 alkoxy, C1-C6 haloalkoxy, —C(O)OR2a, C3-C6 cycloalkyl, 3- to 6-membered heterocyclyl, C6 aryl, 5- to 6-membered heteroaryl, —(C1-C3 alkylene)C6 aryl or C1-C6 alkyl optionally substituted by oxo, halogen, —OR2a or —NR2aR2b, wherein C3-C6 cycloalkyl, 3- to 6-membered heterocyclyl, C6 aryl, 5- to 6-membered heteroaryl, —(C1-C3 alkylene)C6 aryl of R2 optionally substituted by C1-C6 alkyl;
• or R1 and R2 are taken together with the atom to which they are attached to form a C3-C6 cycloalkyl or 3- to 6-membered heterocyclyl, each of which is optionally substituted by oxo, —OH, halogen, —NH2, or C1-C6 alkyl optionally substituted by oxo, —OH, halogen or —NH2;
• R2a and R2b are independently hydrogen or C1-C6 alkyl;
• R3 and R4 are independently hydrogen, halogen, or C1-C6 alkyl optionally substituted by oxo, —OH or halogen;
• or R3 and R4 are taken together with the atom to which they are attached to form a C3-C6 cycloalkyl or 3- to 6-membered heterocyclyl, each of which is optionally substituted by oxo, —OH, -halogen, —NH2, or C1-C6 alkyl optionally substituted by oxo, —OH, halogen or —NH2;
• R5 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 6-membered heterocyclyl, C6 aryl, 5- to 6-membered heteroaryl, —CN, halogen, C1-C6 alkoxy, C1-C6 haloalkoxy, —OR10, —SR10, —S(O)2R10, —S(O)2NR11R12, —NR10S(O)2R11, —NR11R12, —C(O)R10, —NR10C(O)R11, —NR10C(O)NR11R12, —C(O)OR10, —C(O)ONR11R12, —C(O)NR11R12, wherein each of which is optionally substituted by R8;
• each R6a and R6b is independently oxo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 6-membered heterocyclyl, C6 aryl, —CN, halogen, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, —OR13, —SR13, —S(O)2R13, —S(O)2NR14R15, —NR13S(O)2R14, —NR14R15, —C(O)R13, —NR13C(O)R14, —NR13C(O)NR14R15, —C(O)OR13, —C(O)ONR14R15, —C(O)NR14R15, —(C1-C3 alkylene)OR13, —(C1-C3 alkylene)SR13, —(C1-C3 alkylene)S(O)2R13, —(C1-C3 alkylene)S(O)2NR14R15, —(C1-C3 alkylene)NR13S(O)2R14, —(C1-C3 alkylene)NR14R15, —(C1-C3 alkylene)C(O)R13, —(C1-C3 alkylene)NR13C(O)R14, —(C1-C3 alkylene)NR13C(O)NR14R15, —(C1-C3 alkylene)C(O)OR13, —(C1-C3 alkylene)C(O)ONR14R15, —(C1-C3 alkylene)(C3-C8 cycloalkyl) or —(C1-C3 alkylene)(3- to 10-membered heterocyclyl);
• wherein each of R6a and R6b is independently optionally substituted by oxo, C2-C6 alkenyl, C2-C6 alkynyl, —CN, halogen, C1-C6 alkoxy, C1-C6 haloalkoxy, —OR16, —SR16, —S(O)2R16, —S(O)2NR17R18, —NR16S(O)2R17, —NR17R18, —C(O)R16, —NR16C(O)R17, —C(O)OR16, C1-C6 alkyl optionally substituted by oxo, OH, halogen or NH2;
• R7 and R7′ are independently hydrogen, C3-C6 cycloalkyl or C1-C6 alkyl optionally substituted by halogen or —OH;
• or R7 and R7′ are taken together with the atom to which they are attached to form a C3-C6 cycloalkyl;
• R8 is halogen, oxo, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl 3- to 6-membered heterocyclyl, —CN, C1-C6 alkoxy, C1-C6 haloalkoxy, —OR16, —SR16, —S(O)2R16, —S(O)2NR17R18, —NR16S(O)2R17, —NR17R18, —C(O)R16, —NR16C(O)R17, —C(O)OR16 or C1-C6 alkyl optionally substituted by oxo, —OH, halogen or NH2;
• each R10, R11 and R12 is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl or 3- to 6-membered heterocyclyl, wherein each of R10, R11 and R12 is independently optionally substituted by oxo, C2-C6 alkenyl, C2-C6 alkynyl, —CN, halogen, C1-C6 alkoxy, C1-C6 haloalkoxy, —OR16, —SR16, —S(O)2R16, —S(O)2NR17R18, —NR16S(O)2R17, —NR17R18, —C(O)R16, —NR16C(O)R17, —C(O)OR16 or C1-C6 alkyl optionally substituted by oxo, OH, halogen or NH2;
• or R11 and R12 are taken together with the atom to which they attached to form a 3-6 membered heterocyclyl optionally substituted by oxo, OH, halogen, NH2, or C1-C6 alkyl optionally substituted by oxo, OH, halogen or NH2;
• each R13, R14 and R15 is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 6-membered heterocyclyl, —(C1-C3 alkylene)C3-C6 cycloalkyl or —(C1-C3 alkylene) 5- to 6-heteroaryl, wherein each of R13, R14 and R15 is independently optionally substituted by oxo, C2-C6 alkenyl, C2-C6 alkynyl, —CN, halogen, C1-C6 alkoxy, C1-C6 haloalkoxy, —OR16, —SR16, —S(O)2R16, —S(O)2NR17R18, —NR16S(O)2R17, —NR17R18, —C(O)R16, —NR16C(O)R17, —C(O)OR16 or C1-C6 alkyl optionally substituted by oxo, OH, halogen or NH2;
• or R14 and R15 are taken together with the atom to which they attached to form a 3- to 6-membered heterocyclyl optionally substituted by oxo, OH or halogen, or C1-C6 alkyl optionally substituted by oxo, OH, halogen or NH2;
• each R16, R17 and R18 is independently hydrogen, C2-C6 alkenyl, C2-C6 alkynyl, or C1-C6 alkyl optionally substituted by oxo, OH, halogen or NH2;
• or R17 and R18 are taken together with the atom to which they attached to form a 3- to 6-membered heterocyclyl optionally substituted by oxo, OH, halogen or NH2, or C1-C6 alkyl optionally substituted by oxo, OH, halogen or NH2;
• m and n is independently 0, 1, 2, 3 or 4.