BCL-2 inhibitors

A compound of Formula (A), or an N-oxide thereof, or a pharmaceutically acceptable salt, solvate, polymorph, tautomer, stereoisomer, an isotopic form, or a prodrug of said compound of Formula (A) or N-oxide thereof:

• wherein
• V is N or P(O);
• Q1 is 7-9 membered heterocycloalkyl, 7-9 membered heterocycloalkenyl, or 7-9 membered heteroaryl;
• Q2 is 6-membered heterocycloalkyl, 6-membered heterocycloalkenyl, 6-membered aryl, or 6-membered heteroaryl;
• Q3 is cycloalkyl, cycloalkenyl, bridged cycloalkyl, heterocycloalkyl, heterocycloalkenyl, aryl or heteroaryl;
• Q4 is cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, or heteroaryl;
• Q5 is 6-membered heterocycloalkyl, or 6-membered heterocycloalkenyl;
• Q6 is 6-membered aryl, or 5-6 membered heteroaryl;
• Q7 is 6-membered aryl or 5-6 membered heteroaryl, each of which is optionally fused with a benzene, heteroarene, cycloalkane, cycloalkene, heterocycloalkane, or heterocycloalkene;
• each of R1, R2, R3, R4, R5, R6, R7, R8, R10, and R11, independently, is H, D, alkyl, spiroalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, spiroheterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl, halo, nitro, oxo, cyano, ORa, SRa, alkyl-Ra, NH(CH2)pRa, C(O)Ra, S(O)Ra, SO2Ra, C(O)ORa, OC(O)Ra, NRbRc, C(O)N(Rb)Rc, N(Rb)C(O)Rc, —P(O)RbRc, -alkyl-P(O)RbRc, —S(O)(═N(Rb))Rc, —N═S(O)RbRc, ═NRb, SO2N(Rb)Rc, or N(Rb)SO2Rc, in which said cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl is optionally substituted with one or more Rd;
• R9 is R9A or R9B;
• R9A is H, D, alkyl, spiroalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, spiroheterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl, halo, nitro, oxo, cyano, ORa, SRa, alkyl-Ra, NH(CH2)pRa, C(O)Ra, S(O)Ra, SO2Ra, C(O)ORa, OC(O)Ra, NRbRc, C(O)N(Rb)Rc, N(Rb)C(O)Rc, —P(O)RbRc, -alkyl-P(O)RbRc, —S(O)(═N(Rb))Rc, —N═S(O)RbRc, —NRb, SO2N(Rb)Rc, or N(Rb)SO2Rc, in which said cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl is optionally substituted with one or more Rd;
• R9B is a small molecule E3 ubiquitin ligase binding moiety that binds an E3 ubiquitin ligase;
• Rd, independently, is H, D, alkyl, spiroalkyl, alkenyl, alkynyl, halo, cyano, amine, nitro, hydroxy, ═O, —P(O)RbbRcc, -alkyl-P(O)RbbRcc, —S(O)(═N(Rbb))Rcc, —N═S(O)RbbRcc, ═NRbb, C(O)NHOH, C(O)OH, C(O)NH2, alkoxy, alkoxyalkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkylcarbonyl, alkoxycarbonyl, alkylcarbonylamino, alkylamino, oxo, halo-alkylamino, cycloalkyl, cycloalkenyl, heterocycloalkyl, spiroheterocycloalkyl, heterocycloalkenyl, aryl, or heteroaryl, in which said alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl is optionally substituted with one or more Re;
• Ra, Rb, Rc, Rbb and Rcc, independently, is H, D, alkyl, spiroalkyl, alkenyl, alkynyl, alkoxy, alkoxyalkyl, haloalkyl, hydroxyalkyl, aminoalkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, spiroheterocycloalkyl, heterocycloalkenyl, aryl, or heteroaryl, in which said alkyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl is optionally substituted with one or more Re;
• Re, independently, is H, D, alkyl, spiroalkyl, alkenyl, alkynyl, halo, cyano, amine, nitro, hydroxy, ═O, C(O) NHOH, alkoxy, alkoxyalkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkylcarbonyl, alkoxycarbonyl, alkylcarbonylamino, alkylamino, oxo, halo-alkylamino, cycloalkyl, cycloalkenyl, heterocycloalkyl, spiroheterocycloalkyl, heterocycloalkenyl, aryl, or heteroaryl;
• Z1 is a bond, (CH2)p, N(H), O, S, C(O), S(O2), OC(O), C(O)O, OSO2, S(O2)O, C(O)S, SC(O), C(O)C(O), C(O)N(H), N(H)C(O), S(O2)N(H), N(H)S(O2), OC(O)O, OC(O)S, OC(O)N(H), N(H)C(O)O, N(H)C(O)S, N(H)C(O)N(H), (CH2)pN(H)(CH2)q, (CH2)pN(H)C(O)(CH2)q, (CH2)pC(O)N(H)(CH2)q, OC(O)N(H)(CH2)p+1N(H)(CH2)q, a bivalent alkenyl group, or a bivalent alkynyl group;
• L is L1 or L2;
• L1 is bond, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, or heteroaryl, in which said alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, or heteroaryl is optionally substituted with one or more Rd;
• L2 is an alkyl in which one or more -Li- are optionally inserted between any two adjacent carbon atoms;
• -Li- is —N(Ra)—, —O—, —S—, —C(O)—, —S(O2)—, —OC(O)—, —C(O)O—, —OSO2—, —S(O2)O—, —C(O)S—, —SC(O)—, —C(O)C(O)—, —C(O)N(Ra)—, —N(Ra)C(O)—, —S(O2)N(Ra)—, —N(Ra)S(O2)—, —OC(O)O—, —OC(O)S—, —OC(O)N(Ra)—, —N(Ra)C(O)O—, —N(Ra)C(O)S—, —N(Ra)C(O)N(Ra)—, a bivalent alkenyl group, a bivalent alkynyl group, a bivalent cycloalkyl group, a bivalent heterocycloalkyl group, a bivalent aryl group, a bivalent heteroaryl group;
• W is O or N(Ra);
• two of R1 group, taken together with the atoms to which they are attached, may optionally form a cycloalkyl or heterocycloalkyl, in which said cycloalkyl or heterocycloalkyl of R1, is optionally substituted with one or more Rd;
• two of R2 group, taken together with the atom(s) to which they are attached, may optionally form a cycloalkyl or heterocycloalkyl, in which said cycloalkyl or heterocycloalkyl of R2, is optionally substituted with one or more Rd;
• R3 and R4 group, taken together with the atom to which they are attached, may optionally form a cycloalkyl or heterocycloalkyl, in which said cycloalkyl or heterocycloalkyl of R3 and R4, is optionally substituted with one or more Rd;
• two of R5 group, taken together with the atom(s) to which they are attached, may optionally form a cycloalkyl or heterocycloalkyl, in which said cycloalkyl or heterocycloalkyl of R5, is optionally substituted with one or more Rd;
• two of R6 group, taken together with the atoms to which they are attached, may optionally form a cycloalkyl or heterocycloalkyl, in which said cycloalkyl or heterocycloalkyl of R6, is optionally substituted with one or more Rd;
• two of R7 group, taken together with the atoms to which they are attached, may optionally form a cycloalkyl or heterocycloalkyl, in which said cycloalkyl or heterocycloalkyl of R7, is optionally substituted with one or more Rd;
• two of R10 group, taken together with the atom(s) to which they are attached, may optionally form a cycloalkyl or heterocycloalkyl, in which said cycloalkyl or heterocycloalkyl of R10, is optionally substituted with one or more Rd;
• two of R11 group, taken together with the atom(s) to which they are attached, may optionally form a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, in which said cycloalkyl, heterocycloalkyl, aryl, or heteroaryl of R11, is optionally substituted with one or more Rd;
• R2 and R5 group, taken together with the atoms to which they are attached, may optionally form a cycloalkyl or heterocycloalkyl, in which said cycloalkyl or heterocycloalkyl of R2 and R5, is optionally substituted with one or more Rd;
• R3 and R5 group, taken together with the atoms to which they are attached, may optionally form a cycloalkyl or heterocycloalkyl, in which said cycloalkyl or heterocycloalkyl of R3 and R5, is optionally substituted with one or more Rd;
• Rb and Rc group, taken together with the atom to which they are attached, may optionally form a cycloalkyl, or heterocycloalkyl, in which said cycloalkyl or heterocycloalkyl of Rb and Rc, is optionally substituted with one or more Re;
• two of Rd group, taken together with the atom(s) to which they are attached, may optionally form a cycloalkyl, or heterocycloalkyl, in which said cycloalkyl or heterocycloalkyl of Rd, is optionally substituted with one or more Re;
• two of Re group, taken together with the atom(s) to which they are attached, may optionally form a cycloalkyl or heterocycloalkyl, in which said cycloalkyl or heterocycloalkyl of Re is optionally substituted with one or more groups selected from H, D, alkyl, alkenyl, alkynyl, halo, cyano, amine, nitro, hydroxy, C(O)NHOH, alkoxy, alkoxyalkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkylcarbonyl, alkoxycarbonyl, alkylcarbonylamino, alkylamino, oxo, halo-alkylamino, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, or heteroaryl;
• each of g and j is, independently, 0, 1, 2, or 3;
• each of n, v and k is, independently, 0, 1, 2, 3, 4, 5, 6, 7, or 8;
• s is 0 or 1;
• and
• each of h, m, p, and q is, independently, 0, 1, 2, 3, 4, or 5.