Heterocyclic comipound as cdk-hdac dual pathway inhibitor

A compound of the following formula (I), or the deuterated derivative at any possible position in the molecule, diastereomers, and enantiomers (if any) thereof:

• or the pharmaceutically acceptable salts, prodrugs, hydrates, solvates thereof, wherein
• is phenyl ring, 5- to 6-membered monocyclic heteroaromatic ring, or 8- to 10-membered fused heteroaromatic ring (including aromatic-aromatic fused ring, aromatic-(saturated or unsaturated alkane rings or heterocyclic ring) fused ring), the mono-heteroaromatic ring and bicyclic heteroaromatic ring described herein may optionally comprise 1 to 5 heteroatoms independently selected from N, O, and S;
• A is a bond, —O—, —C(O)—, —(CR6R7)m—, C2-8 alkenylene, C3-8 cycloalkane structure, 3 to 9-membered heterocyclic ring (optionally containing 1-3 heteroatoms selected from N, O, or S), aromatic ring, or heteroaromatic ring;
• the cycloalkane structure, heterocyclic ring, aromatic ring, and heteroaromatic ring can be optionally and independently substituted by 0-4 substituents selected from the group consisting of hydroxy, halogen, C1-4 alkyl, C1-4 haloalkyl, cyano, provided that the chemical structure formed being stable and meaningful;
• when two hydroxyl groups are simultaneously connected to the same carbon atom of the cycloalkane structure or heterocycle, it means that the two hydroxyl groups and the carbon atom form a carbon group (ie, —C(O)—) structure;
• preferably, A is selected from the group consisting of:
• —N(R8)—, —O—, and bicyclic 3- to 9-membered heterocycle (optionally containing 1-3 heteroatoms selected from N, O, S) structure;
• W is chemical bond, —C(O)—, —(CR6R7)m—, —(CR6R7)mNR8—, —N(R8)—, —OC(O)—, —C(O)O—, —C(O)NH—, —NHC(O)—, —S(O)2—, —S(O)2NH—, —NHS(O)2—, C3-8 cycloalkane structure, 3 to 9-membered heterocycle (optionally containing 1-3 heteroatoms selected from N, O, or S), aromatic ring, or heteroaromatic ring;
• with the proviso that
• A, W, V, R4, R5, p and q together form a stable chemical structure;
• when A and W are both bond, (CR4R5)p—V—(CR4R5)qC(O)NH(OH) is directly connected to
• R1 is independently hydrogen, C1-8 alkyl, C3-8 alkenyl, C3-8 alkynyl, C3-8 cycloalkyl, 3- to 9-membered heterocyclic group (optionally containing 1-3 heteroatoms selected from N, O, or S), aryl, or heteroaryl;
• R2 is hydrogen, deuterium, halogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3- to 9-membered heterocyclic group (optionally containing 1-3 heteroatoms selected from N, O, or S), aryl, heteroaryl, CN, NO2, (CR4R5)mOR12, (CR4R5)mSR12, (CR4R5)mN(R13)2, (CR4R5)mC(O)R9, (CR4R5)mC(O)OR12, (CR4R5)mC(O)N(R13)2, (CR4R5)mOC(O)R9, (CR4R5)mOC(O)OR12, (CR4R5)mOC(O)N(R13)2, (CR4R5)mNR8C(O)R9, (CR4R5)mNR13C(O)OR12, (CR4R5)mNR13C(O)N(R13)2, (CR4R5)mS(O)R9, and (CR4R5)mS(O)2R9;
• R3 is hydrogen, deuterium, halogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3- to 9-membered heterocyclic group (optionally containing 1-3 heteroatoms selected from N, O, or S), aryl, heteroaryl, OR6, NR6R7, or CN;
• each R4 and R5 is independently hydrogen, deuterium, halogen, or C1-4 alkyl;
• or R4 and R5 together with the carbon atom they attached to form a 3- to 9-membered cyclic structure which optionally containing 0-3 additional heteroatoms selected from N, O, or S);
• or R4 and R5 together with the carbon atom they attached to form carbonyl (i.e., CR4R5 is C(O));
• each of R6 and R7 is independently hydrogen, deuterium, halogen, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C3-8 cycloalkyl, 3- to 9-membered heterocyclic (optionally containing 1-3 heteroatoms selected from N, O, or S), aryl, or heteroaryl;
• or R6 and R7 together with the carbon atom they attached form a 3- to 9-membered cyclic structure which optionally containing 0-3 additional heteroatoms each independently selected from N, O, or S;
• R8 is hydrogen, C1-4 alkyl, R9C(O)—, R9S(O)2—, C3-8 cycloalkyl, 3- to 9-membered heterocyclic group (optionally containing 1-3 heteroatoms selected from N, O or S), aryl, or heteroaryl;
• wherein R9 is hydrogen, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C3-8 cycloalkyl, 3- to 9-membered heterocyclic group (optionally containing 1-3 heteroatoms selected from N, O or S), aryl, or heteroaryl;
• V is —CR10R11, —CH═CH—, —C≡C—, —O—, —S—, —N(R8)—, —C(O)—, —OC(O)—, —C(O)O—, —OC(O)O—, —C(O)NH—, —NHC(O)—, —NHC(O)NH—, —S(O)—, —S(O)2—, —S(O)2NH—, —NHS(O)2—, C3-8cycloalkyl, 3- to 9-membered heterocyclic group (optionally containing 1-3 heteroatoms selected from N, O or S), aryl, heteroaryl, or —V1(CR4R5)tV2—;
• wherein R10 and R11 are each independently hydrogen, deuterium, halogen, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C3-8 cycloalkyl, 3- to 9-membered heterocyclic group (optionally containing 1-3 heteroatoms selected from N, O or S), aryl, heteroaryl, —CN, —OR12, —SR12, —N(R13)2, —C(O)R9, —C(O)OR12, —C(O)N(R13)2, —OC(O)R9, —NR13C(O)R9, or —S(O)2R9;
• or R10 and R11 together with the carbon atom they attached to form a 3- to 9-membered cyclic group which optionally containing 0-3 additional heteroatoms selected from N, O or S);
• wherein R12 is hydrogen, C1-4 alkyl, C3-8 cycloalkyl, 3- to 9-membered heterocyclic group (optionally containing 1-3 heteroatoms selected from N, O or S), aryl, or heteroaryl;
• each R13 is hydrogen, C1-4 alkyl, C3-8 cycloalkyl, 3- to 9-membered heterocyclic group (optionally containing 1-3 heteroatoms selected from N, O or S), aryl, or heteroaryl;
• or two R13 together with the nitrogen atom they attached to form a 3- to 9-membered cyclic structure which optionally containing 0-3 additional heteroatoms selected from N, O, or S;
• V1 and V2 are each independently bond, —CR10R11—, —CH═CH—, —C≡C—, —O—, —S—, —N(R8)—, —C(O)NH—, —NHC(O)—, —S(O)2—, —S(O)2NH—, —NHS(O)2—, C3-8 cycloalkyl structure, 3- to 9-membered heterocyclic group (optionally containing 1-3 heteroatoms selected from N, O, or S), aryl, or heteroaryl;
• p and q are each independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
• m is 0, 1, 2, 3, or 4;
• t is 0, 1, 2, 3, 4, or 5;
• with the proviso that the group formed by V, V1, V2, p, q and t being chemically stable structure;
• wherein each of the above mentioned alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic group, aryl, heteroaryl, cycloalkane structure, heterocyclic, aromatic cyclic and heteroaryl cyclic are optionally and each independently substituted by 1-3 substituents selected from the group consisting of deuterium, halogen, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C3-8 cycloalkyl, 3- to 9-membered heterocyclic group (optionally containing 1-3 heteroatoms selected from N, O or S), aryl, heteroaryl, —CN, —NO2, —OR12, —SR12, —N(R13)2, —C(O)R9, —C(O)OR12, —C(O)N(R13)2, —SO2N(R13)2;
• in the substituents, the definition of each group is as described above;
• unless otherwise specified, the above aryl group is aryl group having 6 to 12 carbon atoms;
• the heteroaryl group and heteroaryl cyclic is 5- to 15-membered heteroaryl group comprising hetero atom.
• with the proviso that the compound is other than these structures: