Substituted Piperazine Compounds And Methods Of Use Thereof

A compound having Formula (I) or a stereoisomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof,

• wherein
• X is
• wherein U4 is CR2 or N:
• p is 1, 2 or 3;
• W is —NH—, —O— or —S—;
• each L is —CR3R4—;
• each L2 is —CR5R6—;
• t is 0, 1 or 2;
• r is 1, 2, 3, 4 or 5;
• q is 1, 2, 3 or 4;
• Y is
• wherein Q is O, S or N(R7);
• each of and is independently a single bond or a double bond;
• each of X1, X2, X3 and X4 is independently —O—, —S—, CR8, N, —CR8R8a— or —NR8b—;
• or X1 and X2 together or X3 and X4 together independently form —CR8R8a—, —NR8b—, —O— or —S—;
• each R1 is independently H, D, F, Cl, Br, I, —CN, —N3, —NO2, —NRaRb, —ORc, alkyl, alkenyl or alkynyl, wherein each of alkyl, alkenyl and alkynyl is optionally and independently substituted with one or more R9;
• each R2 is independently H, D, F, Cl, Br, I, —CN, —N3, —NO2, —NRaRb, —ORc, —S(═O)mRc, —C(═O)Rc, —C(═O)ORc, —C(═O)NRaRb, —S(═O)2NRaRb, —OC(═O)Rc, —N(Ra)C(═O)Rc, alkyl, alkenyl or alkynyl, wherein each of alkyl, alkenyl and alkynyl is optionally and independently substituted with one or more R9;
• each R3 and R4 is independently H, D, F, Cl, Br, I, —CN, —N3, —NH2, —OH, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, cycloalkyl, heterocyclyl, aryl or heteroaryl, or R3 and R4, together with the carbon atom to which they are attached, form a carbonyl group, a carbocyclic ring or a heterocyclic ring, wherein each of alkyl, alkenyl, alkynyl, alkoxy, alkylamino, cycloalkyl, heterocyclyl, aryl, heteroaryl, the carbocyclic ring and the heterocyclic ring is optionally and independently substituted with one or more R9;
• each R5 and R6 is independently H, D, F, Cl, Br, I, —CN, —N3, —NH2, —OH, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, cycloalkyl, heterocyclyl, aryl or heteroaryl, or R5 and R6, together with the carbon atom to which they are attached, form a carbocyclic ring or a heterocyclic ring, wherein each of alkyl, alkenyl, alkynyl, alkoxy, alkylamino, cycloalkyl, heterocyclyl, aryl, heteroaryl, the carbocyclic ring and the heterocyclic ring is optionally and independently substituted with one or more R9;
• R7 is H, —OH, —NH2, C1-C4 alkyl, C1-C4 haloalkyl or C1-C4 alkylamino;
• each R8, R8a and R8b is independently H, D, F, Cl, Br, I, —CN, —N3, —NO2, —(C0-C6 alkylene)-NRaRb, —(C0-C6 alkylene)-ORc, —(C0-C6 alkylene)-S(═O)mRc, —C(═O)Rc, —C(═O)ORc, —C(═O)NRaRb, —S(═O)2NRaRb, —OC(═O)Rc, —N(Ra)C(═O)Rc, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl;
• or two R8 on two adjacent ring atoms, or two R8b on two adjacent ring atoms, or R8 and R8b on two adjacent ring atoms, together with the ring atoms to which they are attached, independently form a carbocyclic ring, a heterocyclic ring, an aryl ring or a heteroaryl ring, wherein each of the carbocyclic ring, the heterocyclic ring, the aryl ring and the heteroaryl ring is optionally and independently substituted with one or more substituents independently selected from Rx and Ry;
• each R9 is independently F, Cl, Br, I, —CN, —N3, —NO2, —OH, —SH, —NH2, alkyl, haloalkyl, alkoxy, alkylthio or alkylamino;
• each Rx and Ry is independently H, D, F, Cl, Br, I, —CN, —N3, —NO2, —NRaRb, —ORc, —SRc, —C(═O)NRaRb, —C(═O)ORc, —O—(C0-C6 alkylnene)-C(═O)NRaRb, —O—(C0-C6 alkylene)-C(═O)ORc, alkyl or haloalkyl;
• each Ra and Rb is independently H, alkyl, alkenyl, alkynyl, haloalkyl, —(C0-C6 alkylene)-cycloalkyl, —(C0-C6 alkylene)-heterocyclyl, —(C0-C6 alkylene)-aryl or —(C0-C6 alkylene)-heteroaryl, or Ra and Rb, together with the nitrogen atom to which they are attached, form a heterocyclic ring;
• each Rc is independently H, alkyl, alkenyl, alkynyl, haloalkyl, —(C0-C6 alkylene)-cycloalkyl, —(C0-C6 alkylene)-heterocyclyl, —(C0-C6 alkylene)-aryl or —(C0-C6 alkylene)-heteroaryl;
• and
• each m is independently 0, 1 or 2.